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1 Allergy & Immunology Niket Sonpal, MD Chief Resident Lenox Hill Hospital‐NSLIJ Assistant Clinical Professor ‐ Touro College of Medicine Allergy & Immunology Anaphylaxis Angioedema Urticaria Allergic Rhinitis Primary Immunodeficiency  Disorders Anaphylaxis  • Worst form of acute allergic reaction • Synonymous with immediate hypersensitivity • Pathogenesis – Initial sensitization to antigen with subsequent re- exposure – Upon re-exposure, IgE binds to mast cells leading to release of their granules (e.g., histamine, prostaglandins, and leukotrienes) – Results in abnormalities that essentially define anaphylaxis MTB S2CK  ‐ p. 41 Anaphylaxis Initial sensitization to antigen Upon re-exposure, IgE binds to mast cells leading to release of their Sensitization Re-exposure Anaphylaxis • Hives • Itching • Constriction of airways DEATH MTB S2CK  ‐ p. 41 granules HISTAMINE LEUKOTRIENES PROSTAGLANDINS • Swollen tongue • Wheezing • Dyspnea • Tachycardia • Nausea, vomiting, or diarrhea • Dizziness or fainting • Hypotension Anaphylaxis  Anaphylactoid Reactions No presensitization to antigen Identical Tx MTB S2CK  ‐ p. 41 Non-IgE related Anaphylaxis/Etiology • Causes of anaphylaxis = causes of any allergic event – Insect bites and stings – Medications: penicillin, phenytoin, lamotrigine, quinidine, rifampin, and sulfa Foods– Foods – Latex is a very important cause of anaphylaxis in healthcare workers MTB S2CK  ‐ p. 41 2 Anaphylaxis/Presentation  Characterized by • Hypotension • Tachycardia • Respiratory: stridor • RashRash MTB S2CK  ‐ p. 41‐42 Source: Fashad Bagheri. MD Anaphylaxis/Treatment The best initial treatment is • A – Airway Protection – Intubation – Cricothyroidodotomy • B – Breathingg • C - Circulation – Epinephrine – – Antihistamines – H1 and H2 – Glucocorticoids MTB S2CK  ‐ p. 42 Angioedema • Angioedema is sudden swelling of − Face − Tongue − Eyes − Airway • This can be from deficiency of C1 esterase inhibitor Look for recent start of ACE inhibitors preceding symptoms This can be from deficiency of C1 esterase inhibitor • Characteristic association of onset with minor physical trauma • Angioedema often idiopathic MTB S2CK  ‐ p. 42 Angioedema/Presentation • Hereditary angioedema is a genetic disorder • Glucocorticoids• Glucocorticoids don’t work MTB S2CK  ‐ p. 43 Source: commons.wikimedia.org Angioedema/Tests • The best initial test... – C2 and C4 levels in complement pathway • Will be decreased – C1 esterase inhibitor • Also decreased • 3 types of hereditary angioedema3 types of hereditary angioedema – Type I - decreased levels of C1INH (85%) – Type II - normal levels but decreased function of C1INH (15%) – Type III - no detectable abnormality in C1INH MTB S2CK  ‐ p. 43 Angioedema/Treatment Ensure airway • Fresh frozen plasma E ll tid Acute Tx Long Term Tx Androgens • Danazole Airway MTB S2CK  ‐ p. 43 protection first • Ecallantide And • Stanazole 3 Urticaria • Form of allergic reaction that causes sudden swelling of superficial skin layers • Can be caused by • Insects • Medications • Pressure • Cold • Vibration MTB S2CK  ‐ p. 43 Source: commons.wikimedia.org Urticaria/Treatment 1. Antihistamines – Hydroxyzine, diphenhydramine, fexofenadine, loratidine, cetirizine, or ranitidine 2 L k t i t2. Leukotriene receptor antagonists – Montelukast or zafirlukast MTB S2CK  ‐ p. 44 Source: commons.wikimedia.org Allergic Rhinitis • IgE-dependent triggering of mast cells • Seasonal allergies such as “hay fever” are common • Presents with recurrent episodes of – Watery eyes, sneezing, itchy nose, and y y , g, y , itchy eyes – Inflamed, boggy nasal mucosa – Pale or violaceous turbinates – Nasal polyps MTB S2CK  ‐ p. 44 Allergic Rhinitis/Diagnostic Tests  • Diagnosed clinically • Skin testing and blood testing • IgE levels may be elevated • Nasal smear with  eosinophils MTB S2CK  ‐ p. 44 Source: commons.wikimedia.org Allergic Rhinitis/Treatment 1. Prevention & avoidance 2. Intranasal corticosteroid sprays 3. Antihistamines – H1 blockers 4. Intranasal anticholinergic medications 5. Desensitization to allergens MTB S2CK  ‐ p. 44 Common Variable Immunodeficiency (CVID)  • B cells are present but decreased Igs • Decrease in all Ig subtypes – IgG, IgM, and IgA LOW B cells output, normal T cells MTB S2CK  ‐ p. 45 4 Common Variable Immunodeficiency (CVID)  • Recurrent sinopulmonary infections • Frequent episodes of – Bronchitis – Pneumonia – Sinusitis AndAnd – Otitis media • Other manifestations are – Giardiasis – Sprue-like intestinal malabsorption MTB S2CK  ‐ p. 45 Common Variable Immunodeficiency (CVID)  Clue to CVID is a decrease in the output of B lymphocytes with a normal number of B cells as well as normalnumber of B cells as well as normal amounts of lymphoid tissue (e.g., nodes, adenoids, and tonsils) MTB S2CK  ‐ p. 45 Common Variable Immunodeficiency (CVID)  • Immunoglobulin levels –Decreased • Antigen Stimulation –Decreased response –Normal Number of B Cells MTB S2CK  ‐ p. 45 Common Variable Immunodeficiency (CVID)  Treatment • Antibiotics are used for each infection as it develops • Chronic maintenance Reg lar inf sions of IVIG– Regular infusions of IVIG MTB S2CK  ‐ p. 45 X‐linked (Bruton) Agammaglobulinemia • Low B, normal T in males • Male children with increased sinopulmonary infections • B cells and lymphoid tissues are diminished • T cells are normal • Treatment: Abx for infections as they arise• Treatment: Abx for infections as they arise • Long-term regular administration of IVIG keeps children healthier LOW B cells, normal T cells in young male children MTB S2CK  ‐ p. 45 Severe Combined Immunodeficiency • LOW B AND LOW T • The word “combined” in severe combined immunodeficiency (SCID) means that there is deficiency in both B and T cells – Results in infections related to both deficiencies LOW B cells and LOW T cells. Analogous to HIV MTB S2CK  ‐ p. 46 5 Severe Combined Immunodeficiency B cells • Decreased Ig production T cells • Markedly decreased numbers of T cells Long-Term Treatment • Bone marrow transplant MTB S2CK  ‐ p. 46 IgA Deficiency • These patients present with recurrent sinopulmonary infections The difference with this syndrome is: • Atopic diseases • Anaphylaxis to blood transfusion when blood donor has normal levels of IgAhas normal levels of IgA • Sprue-like condition with fat malabsorption • Increase in risk of vitiligo, thyroiditis, and rheumatoid arthritis MTB S2CK  ‐ p. 46 IgA Deficiency • Treat infections as they arise • Washed blood transfusions – otherwise anaphylaxis • IVIG injections will not work Th t t f I A i IVIG• The trace amounts of IgA in IVIG may provoke anaphylaxis MTB S2CK  ‐ p. 46 Hyper IgE Syndrome • Presents with recurrent skin infections due to Staphylococcus • Treat infections as they arise • Consider prophylactic antibiotics (e.g., dicloxacillin or cephalexin) MTB S2CK  ‐ p. 46 Source: wikimedia commons Wiskott‐Aldrich Syndrome • Normal T cells normal B cells – decline with age • Immunodeficiency combined with thrombocytopenia and eczema • T lymphocytes markedly deficient in blood and lymph nodes • Bone marrow transplantation is only definitiveBone marrow transplantation is only definitive treatment Normal T cells normal B cells – decline with age MTB S2CK  ‐ p. 46 Chronic Granulomatous Disease (CGD)  • CGD is genetic disease resulting in extensive inflammatory reactions • Leads to lymph nodes with purulent material leaking out MTB S2CK  ‐ p. 46 6 Chronic Granulomatous Disease (CGD)  • Aphthous ulcers And • Inflammation of nares is common MTB S2CK  ‐ p. 46 Source:commons.wikimedia.org Chronic Granulomatous Disease (CGD)  • Granulomas may become obstructive in the GI or urinary tract • Look for infections with odd combination of: −StaphylococcusStaphylococcus −Burkholderia −Nocardia −Aspergillus MTB S2CK  ‐ p. 46‐47 Chronic Granulomatous Disease (CGD)  • Abnormal nitroblue tetrazolium testing – This is a decrease in NADPH oxidase, which generates superoxide – CGD test is negative MTB S2CK  ‐ p. 47 Primary Immunodeficiency Disorders CVID • LOW B cell output • Normal T cells X-linked (Bruton) Agammaglobulinemia LOW B cells normal T cells in young male children • LOW B & T cells • Analogous to HIV SCID IgA Deficiency • Atopic • Anaphylaxis MTB S2CK  ‐ p. 45‐47 Hyper IgE Syndrome • Normal T cells • Normal B cells • Low Platelets • Eczema Wiskott-Aldrich Syndrome Skin infections • Staphylococcus Lymph nodes with purulent material Infections, combined with • Staphylococcus • Burkholderia • Nocardia • Aspergillus CGD 1 The Cardiovascular System Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Coronary Artery  Disease – Part 1  D fi itiDefinition Risk Factors Clinical Presentation Coronary Artery Disease (CAD)/Definition • Can be used interchangeably with: – Atherosclerotic heart disease – Ischemic heart disease • All imply insufficient perfusion of coronary arteriescoronary arteries • Abnormal narrowing of vessels • Insufficient oxygen delivery to myocardial tissue MTB S2CK  ‐ p. 49 48-year-old woman in office with chest pain for several weeks. Pain isn't reliably related to exertion. No pain now. The pain is retrosternal and sometimes associated with nausea. No SOB and no radiation beyond chest. She has no past medical history. What is the most likely diagnosis? a. Gastroesophageal reflux disease (GERD) b. Unstable angina c. Pericarditis d. Pneumothorax e. Prinzmetal angina MTB S2CK  ‐ p. 49  Sharp, pleuritic pain, tracheal deviation Pain worse with lying down, better when sitting up Nonexertional chest pain, early in morning, ST segment elevation Acute, severe pain in ED Menstruating women virtually never have MIs Risk Factors for CAD Risk factors are most important with equivocal or uncertain histories Women > men eventually die of heart disease MTB S2CK  ‐ p. 50 equivocal or uncertain histories Which of the following is most likely to benefit a patient’s risk of coronary disease? a. Administration of estrogen replacement at time of menopause b Stopping tamoxifen Tamoxifen unrelated to CAD Estrogen simply does NOT help CAD b. Stopping tamoxifen c. Stopping aromatase inhibitors d. Regular exercise e. Relaxation methods (e.g., meditation) MTB S2CK  ‐ p. 50  Good, but immeasurable, no evidence of proven benefit Zero relationship to CAD Tamoxifen unrelated to CAD 2 Risk Factors for CAD Clear ones: • Diabetes mellitus • Tobacco smoking • HTN • Hyperlipidemia• Hyperlipidemia • Family history of premature CAD • Age > 45 men; > 55 women MTB S2CK  ‐ p. 50 Risk Factors for CAD Diabetes (worst risk) HTN • Defined as > 140/90 • More common than diabetes • 20% of total population (60 million people) with HTN • 50% unaware they’re hypertensive MTB S2CK  ‐ p. 50 Risk Factors for CAD Family history not a risk if… • CAD developed in elderly relatives • Relatives were grandparents, cousins, or aunts and uncles Family history is a risk ONLY if…y y • First-degree relatives (siblings/parents) • Premature disease: • Defined as: – Male relative < 55 – Female relative < 65 MTB S2CK  ‐ p. 50‐51 Which of the following is the most dangerous to a patient in terms of risk for CAD? a. Elevated triglycerides b. Elevated total cholesterol D d HDL Triglycerides not as dangerous as elevated LDL It’s not the TOTAL cholesterol l HDL it’ LDL!c. Decreased HDL d. Elevated LDL e. Obesity MTB S2CK  ‐ p. 51  The danger of obesity is from its association with high LDL, DM, and HTN or low HDL, it’s LDL! Risk Factors for CAD  Less clear • Physical inactivity • Excess alcohol • Insufficient fruits & vegetables • Emotional stress • CT scan calcium scores • Positron emission tomography (PET) scanning MTB S2CK  ‐ p. 51 Postmenopausal woman develops chest pain immediately on hearing news of her son’s death. She develops chest pain, dyspnea, and ST segment elevation in leads V2 to V4. Troponin levels rise with MI. Coronary angiography is normal including an absence of vasospasm. Echocardiography: Apical LV “ballooning” What’s the presumed mechanism of this disorder? a. Absence of estrogen It’s not absent estrogen only causing MIgb. Massive catecholamine discharge c. Plaque rupture d. Platelet activation e. Emboli to coronary arteries MTB S2CK  ‐ p. 52  g y g There were no plaques on angiography Platelets cause MI from CAD, not emotions It would’ve been seen 3 Risk Factors for CAD  Unreliable (Unproven) Risk Factors for CAD • Homocysteine • Chlamydia infection • C-reactive protein • No clear benefit in therapeutic intervention on these factorsthese factors • They’re the wrong answers MTB S2CK  ‐ p. 52 Frequently used wrong answers are just as important to learn as right answers Risk Factors for CAD  The “Most Common Wrong Answer” If risk factor question involves: • Family history • Mistaking CAD in elderly relatives as a risk for patient MTB S2CK  ‐ p. 52 Correcting which of the following risk factors for CAD results in the most immediate benefit? a. Diabetes mellitus b. Tobacco smoking c Hypertension Fixing all of them is good. c. Hypertension d. Hyperlipidemia e. Weight loss MTB S2CK  ‐ p. 53 But… Not as fast as smoking cessation! Chest Pain/Presentation  “What Is the Most Likely Diagnosis?” • Ischemic pain – Dull /“Sore” – Squeezing (Pressure-like) • Like any muscle that’s starved for oxygen • Produces sore-muscle type pain when ischemic • Qualities that go against ischemia – Sharp (“knifelike”) or pointlike – Lasts for few seconds MTB S2CK  ‐ p. 53 Chest Pain/Presentation  • Three features help tell whether or not the pain is ischemic in nature: 1. Changes with respiration (pleuritic) 2. Changes with position of body 3. Changes with touch of chest wall (tenderness) • Each (pleuritic, positional, tender) excludes ischemia with 95% negative predictive value (NPV) MTB S2CK  ‐ p. 53 Chest Pain/Presentation  • < 10% with chest pain in ED end up having an MI • 50% have no cardiac disease at all MCC of chest pain that isn’t MTB S2CK  ‐ p. 53 MCC of chest pain that isn t ischemic in nature is GI related 4 Duration Stable angina: > 2 - < 10 min ACS: > 10 - 30 min Quality Squeezing, tightness, heaviness, pressure, burning, aching NOT: sharp, pins, stabbing, or knifelike Location Substernal Characteristics of Ischemic Pain Provoking factors Physical activity cold Alleviating factors Rest Associated symptoms SOB, nausea, diaphoresis, dizziness, lightheadedness, fatigue  NOT tender  NOT positional  NOT pleuritic Radiation Neck, lower jaw and teeth, arms, shoulders Physical activity, cold, emotional stress Causes of Chest Pain If the case  describes…. Answer as “most  likely diagnosis” Answer as “most  accurate test” Chest wall tenderness Radiation to back, unequal blood pressure between Costochondritis Aortic dissection Physical examination Chest X‐ray with widened mediastinum, chest MTB S2CK  ‐ p. 54 arms Pain worse with lying flat, better when sitting up Pericarditis CTA, MRA, or TEE confirms disease EKG with ST elevation  everywhere, PR  depression Causes of Chest Pain If the case  describes…. Answer as “most  likely diagnosis” Answer as “most  accurate test” Epigastric discomfort,  pain related to eating Bad taste, cough,  Duodenal ulcer  disease Gastroesophageal  Endoscopy Response to PPIs; or  MTB S2CK  ‐ p. 54 , g , hoarseness Cough, sputum,  hemoptysis p g reflux Pneumonia  p ; liquid antacids Chest X‐ray Causes of Chest Pain If the case  describes…. Answer as “most  likely diagnosis” Answer as “most  accurate test” Sudden‐onset, SOB,  tachycardia, hypoxia Sharp, pleuritic pain,  tracheal deviation Pulmonary embolus Pneumothorax Spiral CT, V/Q scan Chest X‐ray MTB S2CK  ‐ p. 54 Chest Pain/Presentation  Features that DON’T help answer the “diagnosis” question • Nausea • Fever SOB (d )• SOB (dyspnea) • Sweating (diaphoresis) • Anxiety MTB S2CK  ‐ p. 54 Coronary Artery  Disease – Part 2  DiagnosisDiagnosis 5 Diagnostic Tests/Electrocardiogram • The “best initial test” for all forms of chest pain is certainly an electrocardiogram (EKG) • In office-based setting: Expect normal EKG–Expect normal EKG But • You can’t do other testing until you know the EKG MTB S2CK  ‐ p. 55 Diagnostic Tests/Enzymes (CK‐MB/Troponin) Cardiac enzymes are not the answer in… • Office/ambulatory case • Chronic or stable chest pain If the patient has acute chest pain then theIf the patient has acute chest pain then the answer is: “Transfer to the emergency department” MTB S2CK  ‐ p. 55 Diagnostic Tests/Enzymes (CK‐MB/Troponin) Enzymes are the answer when: • Acute cases of chest pain • Emergency department MTB S2CK  ‐ p. 55 Diagnostic Tests/Stress Testing Exercise tolerance testing (ETT) is the answer when: • Etiology is unclear and • EKG is not diagnostic ETT without nuclear isotopes: 1. Read EKG 2 Exercise Answer “Stress test” when: Etiology uncertain & EKG not diagnostic2. Exercise • “Exercise” means heart rate > 80% of maximum Maximum heart rate = 220 – patient age MTB SCK  ‐ p. 55 EKG not diagnostic Diagnostic Tests/Stress Testing Thallium (Nuclear) Stress • Normal myocardium picks up thallium like potassium via Na/K-ATPase Myocardium alive & perfused? • Nuclear isotopes will be picked up Abnormalities/Ischemia or Infarction?Abnormalities/Ischemia or Infarction? • Decreased thallium or nuclear uptake Stress or Dobutamine Echo • Normal myocardium moves on echo • Abnormalities decrease wall motion • “Dyskinesis”, ”Akinesis”, or “Hypokinesis” MTB SCK  ‐ p. 56 Diagnostic Tests/Stress Testing Ischemia versus infarction: • Ischemia = Reversible decreased perfusion • Reversal of decrease in thallium uptake or wall motion • It returns to normal after a period of rest • Infarction = Irreversible MTB SCK  ‐ p. 56 Ischemia is reversible wall motion or thallium uptake between rest and exercise. Infarction is irreversible or “fixed.” 6 Diagnostic Tests/Stress Testing Can’t exercise? • Persantine (dipyridamole) or adenosine with nuclear isotopes (e.g., thallium or sestamibi) Or • Dobutamine in combination with echocardiography • Dobutamine increases myocardial oxygen consumptionDobutamine increases myocardial oxygen consumption • Dobutamine provokes ischemia • Ischemia decreases wall motion on echocardiogram MTB SCK  ‐ p. 56 Dipyridamole may provoke bronchospasm. Avoid in asthmatics. Use of Exercise Tolerance Testing Test Indication Ischemia detected Exercise tolerance Exercise thallium Determine presence  of ischemia     Can’t read EKG ST segment depression Decreased uptake of  nuclear isotope MTB S2CK  ‐ p. 56 Exercise echo Dipyridamole thallium Dobutamine echo Can’t read EKG Can’t exercise Can’t exercise p Decreased wall motion Decreased uptake of  nuclear isotope Decreased wall motion Diagnostic Tests/Stress Testing Nuclear and Echo: Sensitivity = Specificity Exercise Thallium = Exercise Echo Dipyridamole Thallium = Dobutamine Echo MTB SCK  ‐ p. 56 Chest pain (likelihood of CHD is high) Resting EKG abnormalities? Chemical stress test Stress YesNo Able to exercise? Yes No ANGIOGRAPHY 1 or 2 vessel disease CABG Stent placement (dipyridamole thallium or dobutamine echo) echocardiogram or nuclear stress test+ 3 vessel disease, left main or 2 vessel disease in diabetics Exercise stress test + + Diagnostic Tests/Coronary Angiography • Detects anatomic location of disease • Determines surgery, angioplasty, or other methods of revascularization • Sometimes used if noninvasive tests are equivocalare equivocal MTB SCK  ‐ p. 56‐57 Diagnostic Tests/Coronary Angiography • Stenosis (narrowing) < 50% of diameter is insignificant • Surgery or angioplasty is done for at least 70% stenosis MTB SCK  ‐ p. 57 7 Diagnostic Tests/Holter Monitoring • Continuous ambulatory EKG monitor • Records rhythm • Usually for 24-hour period • May be for 48 to 72 hours Holter monitor detects rhythm disorders: • A-fib, atrial flutter • Ectopy (e.g., premature beats) • V-tach Holter monitor does not detect ischemia Not accurate for evaluating the ST segment MTB SCK  ‐ p. 57 48-year-old woman comes to office with chest pain occurring over several weeks. Pain isn’t reliably related to exertion. She’s comfortable now. The pain is retrosternal. Past medical history and the EKG is normal. What is the most appropriate next step in management? a. CK-MB b. Troponin E h di Cardiac enzymes evaluate ACS Evaluate valve function wall motion EFc. Echocardiogram d. Exercise tolerance testing e. Angiography f. CT angiography g. Cardiac MRI h. Holter monitor  Detect the anatomic location of stenosis; determines method of revascularization Used for rhythm evaluation Evaluate valve function, wall motion, EF CT Angiogram and MRI not accurate enough Coronary Artery  Disease – Part 3  TreatmentTreatment CAD/Treatment USMLE Step 2 CK is most concerned that you know: Medications that lower mortality • Chronic angina (not an acute coronary syndrome) Aspirin– Aspirin – Beta blockers – Nitroglycerin • Step 2 will not test dosing • Route of administration is tested MTB S2CK  ‐ p. 57 CAD/Treatment  Nitroglycerin: Chronic Stable Angina • Oral • Transdermal patch Acute Coronary SyndromeAcute Coronary Syndrome • Sublingual • Paste • Intravenous MTB S2CK  ‐ p. 58 CAD/Treatment Nonspecific beta blockers (e.g.. propranolol) are not used routinely in cardiology • Clopidogrel – Acute MI (all forms) – Aspirin intolerance (e.g., allergy) – Recent angioplasty with stenting – Adverse effect • Rare thrombotic thrombocytopenic purpura MTB S2CK  ‐ p. 58 8 Treatment/Prasugrel  • Thienopyridine - same class as clopidogrel and ticlopidine Prasugrel: Antiplatelet medication for use in: • Angioplasty & stenting• Angioplasty & stenting • All acute MI • Intolerant of aspirin • ≥75 increased hemorrhagic stroke MTB S2CK  ‐ p. 58 Treatment/ACE Inhibitors • Low EF/systolic dysfunction (best mortality benefit) • Regurgitant valvular disease M t d ff tMost common adverse effect: • Cough –7% of patients –Switch to ARBs MTB S2CK  ‐ p. 58 64-year-old man starts lisinopril for CAD with EF of 24%, and symptoms of breathlessness. He sometimes has rales, but is asymptomatic today. Physical reveals minimal edema of lower extremities. Potassium level is elevated and it’s present on a repeat measurement. EKG is unchanged. How would you best manage the patient? Remove K from the body;You should eliminate the cause a. Add kayexalate (potassium-binding resin) b. Insulin and glucose c. Stop lisinopril d. Switch lisinopril to candesartan e. Switch lisinopril to hydralazine and nitrates MTB S2CK  ‐ p. 58‐59  y; Drive K into the cell, given in acute situation He should get an alternative drug ARBs lead to hyperkalemia Treatment/Lipid Management Statins (HMG-CoA reductase inhibitors) CAD with LDL > 100 mg/dL MTB S2CK  ‐ p. 59 Treatment/Lipid Management LDL > 70: Treat when patient has… Coronary disease AND diabetes • You’re tested on national guidelines from nonbiased federal organizationsg • Not private organizations (e.g., ACC) Everyone will agree: • With CAD, goal of LDL at least < 100 mg/dL MTB S2CK  ‐ p. 59 CAD Equivalents CAD equivalents • Statins to bring LDL down if > 100: –Peripheral artery disease (PAD) –Carotid disease (not stroke) –Aortic disease (aortic artery, not valve) –Diabetes mellitus MTB S2CK  ‐ p. 59 9 Which is the most common adverse effect of statin medications? a. Rhabdomyolysis b. Liver dysfunction c Renal failure The most common wrong answer c. Renal failure d. Encephalopathy e. Hyperkalemia MTB S2CK  ‐ p. 60 They aren’t adverse effects of statins Other Lipid‐Lowering Therapies • Niacin, gemfibrozil, cholestyramine, and ezetimibe all have beneficial effects on lipid profiles • None is “Best initial therapy” • None has clear mortality benefit statins provide • Niacin and fibric acid derivatives such as gemfibrozil have some mortality benefit but not asgemfibrozil have some mortality benefit, but not as much as statins Statins: • Antioxidant effect on endothelial lining of coronary arteries • Gives benefit transcending lowering LDL number MTB S2CK  ‐ p. 60 Niacin  Associated with: • Glucose intolerance • Elevation of uric acid • Uncomfortable “itchiness” from histamine • Niacin is excellent to add to statins if full lipidNiacin is excellent to add to statins if full lipid control not achieved with statins • Although statins, exercise, and cessation of tobacco use will all raise HDL level, niacin will raise HDL somewhat more MTB S2CK  ‐ p. 60 Gemfibrozil  Fibric acid derivatives: • Lower triglyceride levels > statins • Benefit of lowering triglycerides alone not proven as useful as straightforward mortality benefit of statins • Use caution combining fibrates with statins Fibrates + Statins= Increased myositis MTB S2CK  ‐ p. 60 Cholestyramine  • Bile acid sequestrant • Significant interactions with medications in gut • Potentially blocking their absorption Ch l t i i t d ith• Cholestyramine associated with uncomfortable GI complaints • Constipation & flatus MTB S2CK  ‐ p. 60 Ezetimibe  • Definitely lowers LDL No clear benefit to patient • LDL levels are an imperfect marker of benefit with cholesterol-lowering therapies • Ezetimibe: No better than placebo• Ezetimibe: No better than placebo • No Change in MI, stroke, or death MTB S2CK  ‐ p. 60 10 Lipid‐Lowering Therapy Lipid-lowering therapy: What is clear? • Statins lower mortality the most • Questions about adverse effects • Besides the benefit of statins in CAD with LDL levels > 100 mg/dL, the only truly clear t f th th i i th i daspect of other therapies is their adverse effects MTB S2CK  ‐ p. 61 Check AST & ALT with statins Lipid‐Lowering Meds and Adverse Effects Agent Adverse effect Statins Niacin Elevations of transaminases (LFTs),  myositis Elevation in glucose and uric acid level,  Pruritus MTB S2CK  ‐ p. 61 Fibric acid  derivatives Cholestyramine Ezetimibe Increased risk of myositis when combined  with statins Flatus and abdominal cramping Well tolerated and nearly useless Calcium‐Channel Blockers (CCBs) • Dihydropyridine CCBs: –Nifedipine –Nitrendipine –Nicardipine Ni di i–Nimodipine • May increase mortality with CAD because of raising heart rate MTB S2CK  ‐ p. 61 Calcium‐Channel Blockers (CCBs) CCBs are: • Negative inotropes • Should decrease myocardial oxygen consumption • Increased heart rate in the aggregate will gg g increase myocardial oxygen consumption • Bottom line: – Do not routinely use CCBs in CAD MTB S2CK  ‐ p. 61 None of the calcium-channel blockers have been shown to lower morality in CAD Calcium‐Channel Blockers (CCBs) • Verapamil and diltiazem, which do not increase heart rate, are used in those who cannot tolerate beta blockers because of severe asthma • 70% with reactive airway diseases (e g70% with reactive airway diseases (e.g., asthma) still tolerate beta-1 specific BBs MTB S2CK  ‐ p. 61 Calcium‐Channel Blockers (CCBs) Use CCBs (verapamil/diltiazem) in CAD only with: • Severe asthma precluding the use of beta blockers • Prinzmetal variant angina • Cocaine-induced chest pain Adverse Effects of CCBs – Edema – Constipation – Heart block (rare) MTB S2CK  ‐ p. 61‐62 You must know adverse effects 11 Revascularization  Angiography: • Evaluates possibility of revascularization • Either coronary bypass surgery or angioplastyangioplasty • Symptoms alone cannot tell the number of vessels involved MTB S2CK  ‐ p. 62 Coronary Artery Bypass Grafting (CABG) Lowers mortality only with: • Three vessels with > 70% stenosis in each • Left main occlusion T l di ith di b t• Two-vessel disease with diabetes • Persistent symptoms despite maximal medical therapy MTB S2CK  ‐ p. 62 Coronary Artery Bypass Grafting (CABG) • Benefit greatest with left ventricular dysfunction • Internal mammary artery grafts last 10 years • Saphenous vein grafts last 5 years• Saphenous vein grafts last 5 years MTB S2CK  ‐ p. 62 Percutaneous Coronary Intervention (PCI) • Percutaneous coronary intervention (PCI) (angioplasty) • “Intervention” best therapy in acute coronary syndromes • Particularly those with ST segment elevation Mortality benefit of PCI • Much harder to demonstrate in chronic stable angina MTB S2CK  ‐ p. 62 Percutaneous Coronary Intervention (PCI) • Max medical therapy with aspirin, beta blockers, ACEi/ ARBs, and statins has proven benefit that’s ≥ PCI in stable CAD • PCI decreases dependence on medication • Decreasing frequency of angina episodes MTB S2CK  ‐ p. 62 PCI: Best in acute coronary syndromes, particularly with ST segment elevation. PCI doesn’t provide clear mortality benefit for stable patients. Acute Coronary  Syndromes – Part 1 DefinitionDefinition  Presentation  Diagnosis  12 Acute Coronary Syndromes (ACS) Definition • Impossible to determine precise etiology of (ACS) from history & physical alone • Risk factors (e g hypertension diabetes• Risk factors (e.g., hypertension, diabetes mellitus, tobacco) same for CAD MTB S2CK  ‐ p. 62 Acute Coronary Syndrome EKG ST elevation No ST elevation MTB S2CK  ‐ p. 62 STEMI UANSTEMI Cardiac Biomarkers + − NSTEMI (Ischemia) STEMI 70-year-old woman in ED with crushing substernal chest pain for last hour. Pain radiates to left arm and is associated with anxiety, diaphoresis, and nausea. Pain is “sore” and “dull” and clenches fist in front of chest. History of hypertension. Which is most likely in this patient? Pulsus paradoxus, tamponade a. >10 mmHg decrease in BP on inhalation b. Increase in jugular venous pressure on inhalation c. Triphasic scratchy sound d. Continuous “machinery” murmur e. S4 gallop f. Point of maximal impulse displaced to axilla MTB S2CK  ‐ p. 63  p Kussmaul sign: constrictive pericarditisPericardial friction rub: pericarditis PDA (patent ductus) LVH/dilated cardiomyopathy S4 Gallop  13 Acute Coronary Syndromes Increased jugulovenous pressure on inhalation • Kussmaul sign • Constrictive pericarditis Triphasic “scratchy” sound: • Pericardial friction rubPericardial friction rub Dressler syndrome: • Not until several days after MI • Much rarer • Everyone is on aspirin already! MTB S2CK  ‐ p. 63 Acute Coronary Syndromes Continuous “machinery” murmur • Patent ductus arteriosus Displaced point of maximal impulse (PMI) • LVH as well as dilated cardiomyopathy • Displaced PMI is an anatomic abnormality p y • Could not occur with ACS MTB S2CK  ‐ p. 63 Don’t walk into Step 2 without knowing when you will expect each cardiac physical findings No specific physical finding allows you to answer a “most likely diagnosis” question in terms of ST elevation or depression without an EKG 70-year-old woman in ED with crushing substernal chest pain for the last hour. Which EKG finding gives the worst prognosis? a. ST elevation in leads II, III, aVF b. PR interval >200 milliseconds c ST elevation in leads V2 V4 IWMI better prognosis than AWMI First degree AV block c. ST elevation in leads V2-V4 d. Frequent premature ventricular complexes (PVCs) e. ST depression in leads V1 and V2 f. Right bundle branch block (RBBB) MTB S2CK  ‐ p. 63‐64  Benign compared to LBBB Posterior MI PVCs should not be treated, even with acute infarction 70-year-old woman comes to ED with crushing substernal chest pain for the last hour. EKG shows ST segment elevation in V2 to V4. What is the next step in management? a. CK-MB level b. Oxygen c. Nitroglycerin sublingual d. Aspirin e. Thrombolytics Neither of them would be elevated All of them should be given, but neither lowers mortality All will be done, but first aspirin Sh ld b i ti d ’t ttf. Metoprolol g. Atorvostatin h. Angioplasty i. Consult cardiology j. Transfer patient to intensive care unit k. Troponin level l. Morphine m. Angiography MTB S2CK  ‐ p. 64‐65 Start treatment first Never the right answer Should be given, time doesn’t matter Not in acute settings Acute Coronary Syndromes Learn the order in which to do things. Learn the order in which to do things. You must know what is first. MTB S2CK  ‐ p. 65 70-year-old woman comes to ED with crushing substernal chest pain for last hour. EKG shows ST segment elevation in V2 to V4. Aspirin has been given to chew. What is next step in this patient? a. CK-MB level b. Oxygen c. Nitroglycerin sublingual Neither of them would be elevated All of them should be given, but none lowers mortality d. Morphine e. Thrombolytics f. Metoprolol g. Atorvostatin h. Angioplasty i. Troponin level j. Lisinopril MTB S2CK  ‐ p. 65 Angioplasty is superior to thrombolytics BBs and statins should be given, but they are not critically dependent upon time 14 Acute Coronary Syndromes On USMLE Step 2 CK, consultation is almost never the correct choice. Do everything yourself. MTB S2CK  ‐ p. 65 In ACS: Does the treatment lower mortality? Which is most important to do first? ACS/Diagnostic Tests Test Time to being  abnormal Duration of abnormality EKG    Immediately at onset of pain ST elevation progresses  to Q‐waves over days  to a week MTB S2CK  ‐ p. 66 Myoglobin CK‐MB Troponin 1‐4 hours 4‐6 hours 4‐6 hours 1‐2 days 1‐2 days 10‐14 days ACS/Diagnostic Tests Troponin • Can’t distinguish reinfarction several days after the first event • Renal insufficiency gives false positive teststests • Troponin: excreted through the kidney MTB S2CK  ‐ p. 66 Diagnostic Tests/Reinfarction New episode of pain within a few days of the first? • EKG detects new ST segment abnormalities • Check CK-MB levels • After 2 days, the CK-MB level from the initial y , infarction returns to normal • CK-MB elevated several days after initial MI indicates a new ischemic event MTB S2CK  ‐ p. 66 Intensive Care Unit Monitoring • After initial management patient should be in ICU • Continuous rhythm monitoring is essential • Monitoring and rapid cardioversion improves survival – Most common cause of death first several days after myocardial infarction is ventricular arrhythmia (ventricular tachycardia, ventricular fibrillation) – Rapid electrical cardioversion or defibrillation MTB S2CK  ‐ p. 66 Acute Coronary  Syndromes – Part 2 TreatmentTreatment  15 Treatment/STEMI Angioplasty versus Thrombolytics • Angioplasty (PCI) superior to thrombolytics – Better survival and mortality – Less bleeding – Complications of MI decreased – Less arrhythmia, less CHF, fewer ruptures of septum, free wall [tamponade] and papillary muscles [valve rupture] Standard of care: PCI within 90 minutes of arriving in emergency department with chest pain MTB S2CK  ‐ p. 67 “Door to balloon time”: under 90 minutes Treatment/STEMI Complications of PCI • Rupture of coronary artery • Restenosis • Hematoma at entry site into artery • Only 20% of U.S. hospitals can do primary angioplasty • Important to have ability to perform emergency cardiac surgery to repair the vessel MTB S2CK  ‐ p. 67 Which is most important in decreasing the risk of restenosis of the coronary artery after PCI? a. Multistage procedure (i.e., doing 1 vessel at a time, with multiple procedures) b Use of heparin for 3–6 months after the procedure Doesn’t change risk with each vessel done Used only at procedure b. Use of heparin for 3 6 months after the procedure c. Warfarin use after the procedure d. Placement of bare metal stent e. Placement of drug-eluting stent (paclitaxel, sirolimus) MTB S2CK  ‐ p. 67 Has much more risk for restenosis than drug-eluting stent For DVT and PE not coronary disease  Treatment/STEMI Restenosis within 6 Months of PCI • No stent: 30% – 40% • Bare metal stent:15% – 30% • Drug-eluting stent:10% • Can’t use thrombolytics? • Transfer to a facility performing PCI MTB S2CK  ‐ p. 67 Treatment/STEMI Absolute Contraindications to Thrombolytics • Major bleeding: – Bowel (melena), brain • Recent surgery (within the last 2 weeks) • Severe hypertension (>180/110) • Nonhemorrhagic stroke within the last 6 months MTB S2CK  ‐ p. 67‐68 Heme-positive brown stool is not an absolute contraindication to the use of thrombolytics Patient comes to small rural hospital without catheterization lab with chest pain and ST segment elevation. What is the next step in management? a. Transfer for angioplasty Should be done within 90 minutesb. Administer thrombolytics now c. Consult cardiology MTB S2CK  ‐ p. 68 Never the right answer  Time is muscle. Delay = Death “Door to needle time”: under 30 minutes 16 Treatment Indications and Benefits Therapy In what cases is effect greatest? Aspirin Clopidogrel Everyone, “best initial therapy” All MIs, undergoing angioplasty and  stenting MTB S2CK  ‐ p. 68 Beta blockers ACEI/ARBs Everyone, effect not dependent on  time; started any time during  admission Everyone, benefit best with ejection  fraction  100 mg/dL No clear mortality benefit MTB S2CK  ‐ p. 68 Heparin Calcium‐channel  blockers After thrombolytics/PCI to prevent  restenosis, initial therapy with NSTEMI  and unstable angina  Can’t use beta blockers, cocaine‐ induced pain, Prinzmetal angina A man comes to the ED with chest pain for the last hour that is crushing in quality and does not change with respiration or position of his body. EKG: ST segment depression, V2 to V4. Aspirin has been given. What is the next step in this patient? a. Low molecular-weight heparinb. Thrombolytics c. Glycoprotein IIb/IIIa inhibitor (abciximab) d. Nitroglycerin e. Morphine f. Angioplasty g. Metoprolol MTB S2CK  ‐ p. 69 Benefit only with STEMI PCI with stenting No clear benefit Heparin first Should be given, but not urgent Treatment/ST Segment Depression ACS Glycoprotein IIb/IIIa Inhibitors (Abciximab, Tirofiban, Eptifibitide) • Used in acute coronary syndromes • Those who undergo angioplasty and stenting • Not beneficial in acute ST elevation infarctions I hibi l l i• Inhibits platelet aggregation • Reduction in mortality with ST depression, particularly in patients whose troponin or CK-MB levels rise and then develop an MI requiring PCI with stenting MTB S2CK  ‐ p. 69 Summary of Treatment Differences between Cardiac Events Stable angina UA/NSTEMI STEMI Aspirin Beta blockers Nitrates Yes Yes Yes Yes Yes Yes Yes Yes Yes MTB S2CK  ‐ p. 70 Nitrates Heparin GPIIb/IIIa meds Yes No No Yes Yes Yes Yes Yes, only  after  thrombolytics No Summary of Treatment Differences between Cardiac Events Stable angina UA/NSTEMI STEMI Thrombolytics CCBs No No No No Yes, but not as  good as PCI No MTB S2CK  ‐ p. 70 CCBs Warfarin No No No No No No 17 Acute Coronary Syndromes/Treatment Bottom line: 1. tPA (thrombolytics) are beneficial only with STEMI 2. Heparin is best for NSTEMI 3. GPIIb/IIIa inhibitors are best for NSTEMI and those undergoing PCI and stenting Calcium-channel blockers & warfarin: No mortality benefit in ACS LMW heparin superior to unfractionated heparin for mortality benefit MTB S2CK  ‐ p. 70 Treatment/ST Segment Depression ACS In non-ST elevation ACS, when all medications have been given and the patient is not better, urgent angiography and possibly angioplasty (PCI) should be done. “Not better” means MTB S2CK  ‐ p. 70 “Not better” means: • Persistent pain • S3 gallop or CHF developing • Worse EKG changes • Rising troponin levels Acute Coronary Syndromes STEMI Non-STEMI/UA Aspirin/Clopidogrel Beta Blockers Statin ACE Morphine MTB S2CK  ‐ p. 70 p Nitrates Heparin Early PCIPCI If available 180/110) • Nonhemorrhagic stroke last 6 months Complications of Acute MI Excellent source of: “What is the most likely diagnosis?” questions, (most common question on Step 2) All MI complications can result in low BP Hypotension: Not help determine diagnosis MTB S2CK  ‐ p. 71 Complications of Acute MI/Bradycardia Heart rate: Key to establishing diagnosis Sinus bradycardia: • Very common with MI • From ischemia of sinoatrial (SA) node MTB S2CK  ‐ p. 71 Complications of Acute MI/Bradycardia Third-degree (complete) AV block: Cannon “a” waves • Distinguishes 3rd degree block from sinus bradycardia before EKG • From atrial systole against closed tricuspid • Tricuspid valve closed because essence of third-degree block is atria and ventricles contracting separately • Atria/ventricles out of coordination with each other MTB S2CK  ‐ p. 71 18 Complications of Acute MI/Bradycardia • “Cannon” is jugulovenous wave bouncing up into the neck • Look for: right ventricular infarction and third-degree AV block All symptomatic bradycardias:All symptomatic bradycardias: 1. Treated first with atropine 2. Then place pacemaker if the atropine is not effective 3. Pace all permanent 3rd degree blocks MTB S2CK  ‐ p. 71 Complications of Acute MI/Tachycardia Right Ventricular Infarction Look for: New inferior wall MI & clear lungs on auscultation Can’t get blood into lungs if blood can’t enter g g heart • Flip EKG leads from left side to right side of chest Most specific finding: • ST elevation in right lead 4 (RV4) MTB S2CK  ‐ p. 71 Complications of Acute MI/Tachycardia Right coronary supplies: • Right ventricle (RV) • AV node • Inferior wall of the heart • Up to 40% with inferior wall myocardial infarctions (IWMI) have right ventricular infarction • Treat RV infarct with high-volume fluid • Avoid nitroglycerin (markedly worsens filling) MTB S2CK  ‐ p. 71 Complications of Acute MI/Tachycardia Tamponade/Free Wall Rupture • Usually takes several days after infarction for wall to scar & weaken enough for rupture • Look for “sudden loss of pulse” • Lungs: Clear • Cause of Pulseless Electrical Activity (PEA) • Test: Echocardiography • Treat: Pericardiocentesis is done on way into operating room for repair MTB S2CK  ‐ p. 72 Complications of Acute MI/Tachycardia Ventricular Tachycardia/Ventricular Fibrillation • Both can cause sudden death • No way to distinguish without EKG if no pulse • Cardiovert/ Defibrillate MTB S2CK  ‐ p. 72 These complications are the reason patients with acute MI are monitored in an ICU for the first several days after the infarction Complications of Acute MI/Tachycardia Valve or Septal Rupture • Both present with new onset murmur and pulmonary congestion • Mitral regurgitation best heard at apex with radiation to axilla • Ventricular septal rupture best heard at lower leftVentricular septal rupture best heard at lower left sternal border MTB S2CK  ‐ p. 72 Look for a step-up in oxygen saturation as you go from the right atrium to the right ventricle to hand you the diagnosis of septal rupture 19 Complications of Acute MI/Tachycardia Most accurate test: Echocardiogram for both You can’t always depend on buzzwords like “step-up” for oxygenation Often, only numbers are presented: • “42% oxygen saturation found on blood from right atrium and 85% saturation found in right ventricular sample” MTB S2CK  ‐ p. 72 Intraaortic Balloon Pump  Intraaortic balloon pump (IABP): Answer for pump failure from anatomic problem that can be fixed in operating room • IABP contracts & relaxes in sync with natural heartbeat • Helps give a “push” forward to blood IABP is never a permanent device (bridge to surgery) MTB S2CK  ‐ p. 72 Extension of the Infarction/Reinfarction  Second event infarct Look for: • Recurrence of pain • New rales • Bump up in CK-MBs • Sudden onset pulmonary edema Actions: Repeat EKG Re-treat with angioplasty or thrombolytics Continue: aspirin, metoprolol, nitrates, ACE, statins MTB S2CK  ‐ p. 72‐73 Aneurysm/Mural Thrombus  • Detected with echocardiography • Most aneurysms don’t need specific therapy • Mural thrombi are treated with heparin followed by warfarinfollowed by warfarin MTB S2CK  ‐ p. 73 “What is the Most Likely Diagnosis?” Diagnosis Key feature Third‐degree AV  Block Sinus bradycardia Bradycardia, cannon “a”  Waves No cannon “a” waves MTB S2CK  ‐ p. 73 Tamponade/wall  Rupture RV infarction Sudden loss of pulse, JVD IWMI in history, clear lungs,  hypotension “What is the Most Likely Diagnosis?” Diagnosis Key feature Valve rupture Septal rupture New murmur,  rales/congestion New murmur, increase in  MTB S2CK  ‐ p. 73 Ventricular  fibrillation oxygen saturation on  entering the right ventricle Loss of pulse, need EKG to  answer question 20 Preparation for Discharge from Hospital Detection of Persistent Ischemia • Stress test prior to discharge • Stress test determines if angiography needed A i h d t i d f• Angiography determines need for revascularization (angioplasty or bypass surgery) MTB S2CK  ‐ p. 73 Preparation for Discharge from Hospital Everyone should go home on: • Aspirin • Clopidogrel • Beta blockers (metoprolol) • StatinsStatins • ACE inhibitors – Best for anterior wall infarctions because of high likelihood of developing systolic dysfunction MTB S2CK  ‐ p. 74 Dipyridamole is never the right choice for coronary artery disease Preparation for Discharge from Hospital • Clopidogrel: All MIs, or intolerant of aspirin, or post-stenting • ARBs: those with cough to ACE inhibitor • Ticlopidine: for rare person intolerant of both aspirin and clopidogrel MTB S2CK  ‐ p. 74 Prophylactic antiarrhythmic medications: Do not use amiodarone, flecainide, or any rhythm- controlling medication to prevent the development of ventricular tachycardia or fibrillation. Do not be fooled by the question describing “frequent PVCs and ectopy”. Prophylactic antiarrhythmics increase mortality. Sexual Issues Postinfarction  The most commonly tested facts are: • Don’t combine nitrates with sildenafil; hypotension can result because they’re both vasodilators • Erectile dysfunction postinfarction isErectile dysfunction postinfarction is most commonly from anxiety • Most common medication is beta blocker MTB S2CK  ‐ p. 74 Sexual Issues Postinfarction  • Wait after MI for sexual activity –2-6 weeks • If post-MI stress test is normal, any form of exercise program can be started including sexincluding sex MTB S2CK  ‐ p. 74 Congestive Heart Failure Definition  Presentation  Diagnosis  Treatment 21 Congestive Heart Failure (CHF)/Definition • Shortness of breath (dyspnea) - essential feature of congestive heart failure (CHF) • Dysfunction of heart as a pump of blood • Insufficient oxygen delivery and fluid in lungs • Either from: S t li d f tiSystolic dysfunction: • Low Ejection Fraction (EF) and dilation of heart Diastolic dysfunction: • EF is preserved • Heart can’t “relax” and receive blood MTB S2CK  ‐ p. 74‐75 CHF/Causes of Systolic Dysfunction Most Common: • Hypertension resulting in cardiomyopathy • Initially there’s preservation of EF • Over time the heart dilates resulting in• Over time, the heart dilates resulting in systolic dysfunction and low EF • Valvular heart disease of all types results in CHF MTB S2CK  ‐ p. 75 CHF/Causes of Systolic Dysfunction • Myocardial infarction (MI) is a very common cause of dilated cardiomyopathy and decreased EF • “Dead” or infarcted heart won’t pump • CHF most common cause of hospital admission in USA • MI death rate down from: – Thrombolytics – Beta blockers – Angioplasty – Aspirin, clopidogrel • Many are normal, are living with CHF MTB S2CK  ‐ p. 75 CHF/Causes of Systolic Dysfunction Infarction Dilation MTB S2CK  ‐ p. 75 Regurgitation CHF CHF/Causes of Systolic Dysfunction Less common causes are: • Alcohol • Postviral (idiopathic) myocarditis • Radiation • Adriamycin (doxorubicin) use Ch di d th i f ti• Chagas disease and other infections • Hemochromatosis (also causes restrictive cardiomyopathy) • Thyroid disease • Peripartum cardiomyopathy • Thiamine deficiency MTB S2CK  ‐ p. 75 CHF/Presentation In addition to dyspnea on exertion look for: • Orthopnea (worse when lying flat, relieved when sitting up or standing) • Peripheral edema • Rales on lung exam • Jugulovenous distention (JVD)• Jugulovenous distention (JVD) • Paroxysmal nocturnal dyspnea (PND)(sudden worsening at night, during sleep) • S3 gallop rhythm • (Be prepared to identify the sound on Step 2. It may be played.) MTB S2CK  ‐ p. 76‐77 22 Heart Sounds Timing in the Cardiac Cycle MTB S2CK  ‐ p. 76 CHF/Presentation The most frequently asked USMLE Step 2 CK question is: • “What is the most likely diagnosis?” MTB S2CK  ‐ p. 76 “What is the Most Likely Diagnosis?” for Dyspnea Key feature Most likely diagnosis is… Sudden onset, clear lungs Sudden onset, wheezing,  increased expiratory phase Pulmonary embolus Asthma MTB S2CK  ‐ p. 77 Slower, fever, sputum, unilateral  rales/rhonchi Decreased breath sounds  unilaterally, tracheal deviation Pneumonia Pneumothorax “What is the Most Likely Diagnosis?” for Dyspnea Key feature Most likely diagnosis is… Circumoral numbness, caffeine  use, history of anxiety Pallor, gradual over days to  k Panic attack Anemia  weeks Pulsus paradoxus, decreased  heart sounds, JVD Palpitations, syncope Tamponade Arrhythmia  (of almost any kind) MTB S2CK  ‐ p. 77 “What is the Most Likely Diagnosis?” for Dyspnea Key feature Most Likely diagnosis is… Dullness to percussion at base Long smoking history, barrel chest Recent anesthetic use, brown blood  Pleural effusion COPD Methemoglobinemia, not improved with oxygen, clear  lungs on auscultation, cyanosis Burning building or car, wood‐ burning stove in winter, suicide  attempt g Carbon monoxide poisoning MTB S2CK  ‐ p. 77 “What is the Most Likely Diagnosis?” for Dyspnea All of these will lack: • Orthopnea/PND • S3 gallop MTB S2CK  ‐ p. 77 23 CHF/Diagnostic Tests Echocardiography • Most important test of CHF • There is no OTHER way to distinguish Systolic vs. Diastolic dysfunction Will NOT distinguish by: • History • Physical • Tests (e.g., EKG, chest X-ray, or BNP) MTB S2CK  ‐ p. 77 CHF/Ejection Fraction “What is the best initial test?” • Transthoracic echo “What’s the most accurate test?” • Multiple-gated acquisition scan (MUGA) orMultiple gated acquisition scan (MUGA) or nuclear ventriculography Transesophageal echocardiography (TEE): • More accurate for valves MTB S2CK  ‐ p. 78 CHF/Diagnostic Tests When should you answer “nuclear ventriculography”? • Rarely needed • Person receiving chemotherapy with doxorubicindoxorubicin • Trying to give max dose to cure lymphoma • But not cause cardiomyopathy MTB S2CK  ‐ p. 78 CHF/Diagnostic Tests When should you answer BNP? • Acute SOB • Etiology unclear • You can’t wait for echo • Normal BNP excludes CHF MTB S2CK  ‐ p. 78 Tests Used to Determine Etiology of CHF Test Etiology of CHF  EKG Chest X‐ray Holter monitor MI, heart block Dilated cardiomyopathy Paroxysmal arrhythmias MTB S2CK  ‐ p. 78 Cardiac  catheterization CBC Precise valve diameters,  septal defects Anemia Tests Used to Determine Etiology of CHF Test Etiology of CHF  T4/TSH Myocardial biopsy Both high and low thyroid levels  cause CHF Excludes sarcoid, amyloid  Rarely needed MTB S2CK  ‐ p. 78 Swan‐Ganz right heart  catheterization Can biopsy other sites Distinguishes CHF from ARDS; not  routine 24 CHF/Treatment  Systolic Dysfunction (Low EF) • ACE inhibitors or angiotensin receptor blockers (ARBs) • Beta blockers S i l t E l• Spironolactone, Eplerenone • Diuretics • Digoxin MTB S2CK  ‐ p. 79 CHF/Treatment  ACE/ARBs • All patients with systolic dysfunction • All stages of disease • Beneficial effects: any drug in class • When are ARBs “Next best step?” • ACE induced cough MTB S2CK  ‐ p. 79 CHF/Treatment  Beta Blockers • Not clearly any drug in class • Evidence only for: –Metoprolol –Bisoprolol –Carvedilol MTB S2CK  ‐ p. 79 CHF/Treatment  Beta Blockers are: • Anti-ischemic • Decrease heart rate • Decrease O2 consumption • Antiarrhythmic MTB S2CK  ‐ p. 79 Which of the following is the MCC of death from CHF? a. Pulmonary edema b. Myocardial infarction c Arrhythmia/sudden death We can fix this almost all the time CHF doesn’t cause MIc. Arrhythmia/sudden death d. Emboli e. Myocardial rupture MTB S2CK  ‐ p. 79 Clots rare in CHF unless AFib This from MI, not CHF  CHF/Treatment  Spironolactone • Benefit from inhibition of aldosterone • Only proven for more advanced CHF (class III and IV) with dyspnea on minimal exertion or at restminimal exertion or at rest “What is the most common adverse effect?” • Hyperkalemia • Gynecomastia MTB S2CK  ‐ p. 79‐80 25 CHF/Treatment  When is eplerenone the answer? When spironolactone leads to antiandrogenic effects (e.g., gynecomastia) MTB S2CK  ‐ p. 80 CHF/Treatment  Diuretics • ED: Acute pulmonary edema • Office: Combination with ACEi or ARB • Furosemide, torsemide, or bumetanide equal • Spironolactone, although a diuretic, is not Diuretics control symptoms of CHF. They do not lower mortality. used at doses where it has a diuretic effect MTB S2CK  ‐ p. 80 CHF/Treatment  Digoxin • Digoxin does NOT lower mortality in CHF • This is often the single most important question concerning CHF on USMLE Digoxin will: • Control symptoms • Decrease frequency of hospitalizations • No positive inotropic agent (digoxin, milrinone, amrinone, dobutamine) has been proven to lower mortality MTB S2CK  ‐ p. 80 CHF/Treatment  Devices with mortality benefit 1. Implantable defibrillator: Ischemic CM & EF < 35%. Remember: Arrhythmia and sudden death are MCC of death in CHF 2. Biventricular pacemaker: EF < 35% & wide QRS > 120 ms with persistent symptoms MTB S2CK  ‐ p. 80‐81 CHF/Treatment  • Biventricular pacemaker is NOT a dual- chamber pacemaker • Dual-chamber pacer has wire in right ATRIUM and right VENTRICLE • Biventricular pacemaker resynchronizes the heart when there’s a conduction defect • Defers/delays need for cardiac transplantation • Symptoms markedly improved MTB S2CK  ‐ p. 81 CHF/Treatment  Transplantation • Symptoms despite maximal medical therapy (ACE, BB, spironolactone, diuretics, digoxin) and possibly biventricular pacemakerbiventricular pacemaker Warfarin • Always wrong in absence of clot in heart MTB S2CK  ‐ p. 81 26 CHF/Treatment  Mortality Benefit in Systolic Dysfunction • ACEi/ARBs • Beta blockers • Spironolactone • Hydralazine/nitrates MTB S2CK  ‐ p. 81 Calcium-channel blockers (CCBs) can actually raise mortality • Implantable defibrillator CHF/Treatment  Diastolic Dysfunction (CHF with preserved EF) • Less clear • Beta blockers have clear benefit • No mortality benefit in diastolic dysfunction • Digoxin clearly has no benefit MTB S2CK  ‐ p. 81 CHF/Treatment  • Diuretics control symptoms of fluid overload • Do not confuse diastolic dysfunction from hypertrophic CM with hypertrophic obstructive cardiomyopathy (HOCM)obstructive cardiomyopathy (HOCM) • Diuretics are contraindicated in HOCM because they increase obstruction MTB S2CK  ‐ p. 81 Acute Pulmonary Edema Definition  Presentation  Diagnosis  Treatment Acute Pulmonary Edema Definition • Worst (most severe) form of CHF • Rapid fluid accumulation in lungs MTB S2CK  ‐ p. 82 Acute Pulmonary Edema/Presentation How do I answer “What is the most likely diagnosis? Acute shortness of breath with: • Rales • JVD • S3 gallop Ed MTB S2CK  ‐ p. 82 • Edema • Orthopnea MAY be: • Ascites & enlargement of liver/spleen from chronic passive congestion of right side of heart 27 S3 Gallop Rhythm JVD Pitting Edema Wet Crackles ”What is the best initial test?” Brain Natriuretic Peptide (BNP) is the answer if: • Diagnosis not clear • Normal BNP excludes CHF Chest X-ray shows: • Vascular congestion Filli f bl d l t d h d ( h li ti• Filling of blood vessels toward head (cephalization of flow) • Flow mostly at base because of gravity • Enlargement of heart • Effusion MTB S2CK  ‐ p. 82 – 82 Pulmonary Edema Pulmonary edema with cephalization of flow and engorged MTB S2CK  ‐ p. 83 engorged pulmonary veins S ource: S aba A nsari, M D . 28 Acute Pulmonary Edema/Diagnostic Tests Oximetry/Arterial Blood Gas (ABG) • Hypoxia expected • Respiratory alkalosis from hyperventilation CO l il th• CO2 leaves more easily than oxygen enters MTB S2CK  ‐ p. 83 Acute Pulmonary Edema/  Which Test is most likely to alter acute management? Answer!!! EKG • A-fib, Atrial flutter, or V-tach • What to do first?What to do first? • Synchronized cardioversion • Restore atrial systole = Return atrial contribution to cardiac output MTB S2CK  ‐ p. 83 Acute Pulmonary Edema/Diagnostic Tests EKG • Diseased hearts need atrial systole more than normal hearts • Up from 10% to 30 - 40% of cardiac output • Diseased hearts means: Dil t d di th– Dilated cardiomyopathy – Valvular heart disease • If acute pulmonary edema is from arrhythmia fix it fast with….. – Cardioversion!!!!! MTB S2CK  ‐ p. 83 Acute Pulmonary Edema/Diagnostic Tests Echocardiography • MUST be done on all patients • ONLY WAY to determine systolic or diastolic dysfunction • No difference in initial therapy • Huge difference in chronic therapy MTB S2CK  ‐ p. 83 74-woman comes to ED with the acute onset of SOB, RR of 38/minute, rales to apices, S3 gallop, and JVD. What is the best initial step in management? a. Oximeter b. Echocardiography c. Intravenous furosemide Will be done, but first you have to treat Should be done, but not urgently c. Intravenous furosemided. Ramipril e. Metoprolol f. Nesiritide MTB S2CK  ‐ p. 84 Although they are used in CHF, they are not Part of the treatment of acute setting  No mortality benefit. Not better than nitrates Acute Pulmonary Edema/Treatment Preload Reduction Initial therapy: • Oxygen • Loop diuretics (e.g., furosemide or b ti id )bumetinide) • Morphine • Nitrates MTB S2CK  ‐ p. 84 29 Acute Pulmonary Edema/Treatment • The majority in acute pulmonary edema can be managed with preload reduction • Removing 1 to 2 liters of fluid is best • Nesiritide does NOT work better than other agentsother agents MTB S2CK  ‐ p. 84 Acute Pulmonary Edema/Treatment What do you do if the questions say: “Preload reduction hasn’t been effective?” Positive Inotropic Agents • Dobutamine in ICU • Amrinone and milrinone • Phosphodiesterase inhibitors that perform the same role – Increase contractility – Decrease afterload MTB S2CK  ‐ p. 84 Acute Pulmonary Edema/Treatment Positive Inotropic Agents • Digoxin too slow! • Increases contractility, but… • Needs several weeks to work • No benefit of digoxin in acute setting MTB S2CK  ‐ p. 85 Acute Pulmonary Edema/Treatment Afterload Reduction • ACEi and ARBs: • Used on discharge • Long-term use with systolic dysfunction (low EF) • Nitroprusside in ICU • Hydralazine alternate for ACE/ARB MTB S2CK  ‐ p. 85 Heparin is always wrong for acute pulmonary edema, use for clots Valvular Heart Disease Definition  Presentation  Diagnosis  Treatment Valvular Heart Disease/Definition • All can be congenital in nature • Rheumatic fever can lead to any form and mitral stenosis is most common • Aging = Aortic stenosis R it t i HTN & i h i• Regurgitant via HTN & ischemia • Infarction regurgitation • Regurgitation  dilation MTB S2CK  ‐ p. 85 30 Valvular Heart Disease/Presentation • All forms associated with SOB and CHF • Only murmurs are specific for presentation • Right-sided heart lesions (tricuspid and pulmonic valve) increase with inhalation • Inhalation  venous return to right side • Left-sided lesions (mitral and aortic valve)  with exhalation • Exhalation “squeezes” blood out of lungs into left side MTB S2CK  ‐ p. 85 Valvular Heart Disease/Diagnostic Tests • “Best initial test”: Echocardiogram • Transesophageal: more sensitive & specific than transthoracic echo • “Most accurate test”: Catheterization C th t i tiCatheterization: • Most precise valvular diameter • Most exact pressure gradient across valve MTB S2CK  ‐ p. 85 Valvular Heart Disease/Diagnostic Tests EKG: • Not specific with valvular heart disease • Shows hypertrophy of chambers • Cannot confirm diagnosis from EKG Chest X ray:Chest X-ray: • Shows enlargement chambers • Precise anatomic correlation poor • X-ray is neither “the most accurate test” nor “the best initial test” MTB S2CK  ‐ p. 85 Valvular Heart Disease/Treatment • All forms associated with fluid overload • All benefit from diuretics • Meds alone can’t improve stenotic lesions Mit l t i Dil t d ith b ll• Mitral stenosis: Dilated with balloon • Aortic stenosis: Surgical replacement MTB S2CK  ‐ p. 86 Valvular Heart Disease/Treatment Regurgitant lesions • Respond best to vasodilators • ACEi/ARBs, nifedipine, or hydralazine • Surgical replacement must be done before heart dilates too much • If heart dilates excessively valve replacement will not be able to correct decrease in systolic function • If myocardium “stretches” too much it won’t return to normal size and shape MTB S2CK  ‐ p. 86 Valvular Heart Disease/Treatment Assess ventricular size based on: • End-systolic diameter • Ejection fraction • Expansion of end-systolic diameter (must replace the valve)p ) MTB S2CK  ‐ p. 86 Endocarditis prophylaxis is not indicated for any of these valve lesions. 31 Mitral Stenosis (MS) Definition/Etiology • Most often from rheumatic fever • Extremely uncommon in US • Low incidence of acute rheumatic fever • Treatment if symptomatic • Do not treat asymptomatic MS MTB S2CK  ‐ p. 86 Mitral Stenosis Look for: Pregnancy and Immigrant Pregnancy: • 50% increase in plasma volume • Contraction of uterus “squeezes” 500 mL• Contraction of uterus squeezes 500 mL extra into central circulation • Most with MS are immigrants to the US • Come from places where acute rheumatic fever is still common MTB S2CK  ‐ p. 86 Mitral Stenosis Presentation • SOB and CHF AND! • Unique features of presentation: – Dysphagia: Left atrium (LA) presses onDysphagia: Left atrium (LA) presses on esophagus – Hoarseness: LA presses on laryngeal nerve – Atrial fibrillation & stroke from enormous LA – Hemoptysis MTB S2CK  ‐ p. 86‐87 MS: Look for young adult patients Mitral Stenosis/Presentation Enlarged left atrium in mitral stenosis compresses the esophagus causing dysphagia MTB S2CK  ‐ p. 87 S ource: A ndrew P eredo Mitral Stenosis Physical findings • Diastolic murmur after opening snap • Squatting & leg raising increase it! • Increased venous return increases murmur MTB S2CK  ‐ p. 87 Mitral Stenosis – headphones required MTB S2CK  ‐ p. 87 32 Mitral Stenosis Diagnostic tests Echo • TTE: “Best initial test” • TEE more accurate than TTE • Catheterization: “Most accurate test” EKG • Atrial rhythm disturbance, particularly atrial fibrillation, very common • LA hypertrophy: Biphasic P wave: V1 and V2 MTB S2CK  ‐ p. 87 Mitral Stenosis/Diagnostic Tests Diagnostic tests Chest X-ray: Left Atrial Hypertrophy • Straightening of left heart border • Elevation of left main• Elevation of left main- stem bronchus • Second “bubble” behind heart MTB S2CK  ‐ p. 87 – 88 S ource : A ndrew P eredo Mitral Stenosis/Treatment Diuretics & sodium restriction: • When fluid overload present Balloon valvuloplasty • With a catheter Valve replacement O l h h d b d• Only when a catheter procedure cannot be done or fails Warfarin • A-fib to INR 2 to 3 Rate control: Digoxin, beta blockers, or diltiazem/ verapamil MTB S2CK  ‐ p. 88 Aortic Stenosis Definition/Etiology • Congenital bicuspid valve • Increasing calcification with age Presentation • Angina (most common)Angina (most common) • Syncope • CHF: – Poorest prognosis – 2-year average survival MTB S2CK  ‐ p. 88 Aortic Stenosis Murmur • Systolic, crescendo-decrescendo • Peaks in diamond-shape mid-systole • Heard best at 2nd right intercostal spacespace • Radiates to carotids MTB S2CK  ‐ p. 88 Source: Shwan Christian 33 Aortic Stenosis Murmur Valsalva & standing • Decrease intensity of murmur • Less venous return = Less Murmur HandgripHandgrip • Softens murmur • Less blood ejected = Less murmur MTB S2CK  ‐ p. 88 Aortic Stenosis – headphones required MTB S2CK  ‐ p. 88 Aortic Stenosis/Diagnostic Tests • TTE, then TEE, then catheterization • Chest X-ray – Left ventricular hypertrophy • EKG LV hypertrophy (LVH) S V1 + R V5 > 35 mm MTB S2CK  ‐ p. 89 Cardiac enlargement is defined as a heart greater in diameter than 50% of the total transthoracic diameter Source: N ihar Shah, M D . Aortic Stenosis/Treatment Replacement: • Only truly effective therapy for AS • Diuretics  CHF but don’t tolerate volume depletion well Balloon valvuloplastyp y • Not routine for AS • AS calcification doesn’t improve well with balloon valvuloplasty • Only if surgery isn’t an option • Unstable/fragile patients MTB S2CK  ‐ p. 89 Mitral Regurgitation Definition/Etiology • MR is abnormal backward flow of blood through mitral valve that doesn’t fit together • Hypertension• Hypertension • Endocarditis • Myocardial infarction • Papillary muscle rupture • Any heart dilation leads to MR MTB S2CK  ‐ p. 89 Mitral Regurgitation Presentation • Signs/Symptoms of CHF Unique finding: • Pansystolic (holosystolic) murmur • Obscures S1 and S2 • Radiates to axilla • Handgrip worsens murmur of MR • Handgrip increases afterload • Pushes blood backwards • Handgrip worsens AR and MR MTB S2CK  ‐ p. 90 34 Mitral Regurgitation/Presentation • Squatting & leg raising worsen MR • Increase venous return to heart • All left-sided murmurs except mitral valve prolapse (MVP) and hypertrophic obstructive cardiomyopathy willobstructive cardiomyopathy will increase with expiration • MR diagnosed with echo MTB S2CK  ‐ p. 90 Mitral Regurgitation – headphones required MTB S2CK  ‐ p. 90 Mitral Regurgitation Treatment Vasodilators: • ACE or ARBs are best • Decrease rate of progression • Digoxin & diuretics for symptomatic CHF MTB S2CK  ‐ p. 90 Mitral Regurgitation/Treatment Valve replacement: Indicated when heart dilates • Don’t wait for left ventricular end systolic diameter (LVESD) to become large R l h LVESD 40 EF• Replace when: LVESD > 40 mm or EF < 60% • Valve repair: –Placing a clip or sutures across valve to tighten MTB S2CK  ‐ p. 90 Aortic Regurgitation Definition/Etiology AR caused by: Anything that makes the heart or aorta dilate: • MI • HTN • Endocarditis • Marfan syndrome or cystic medial necrosis • Inflammatory disorders (e.g., Ankylosing spondylitis, Reiter syndrome) • Syphilis MTB S2CK  ‐ p. 90‐91 Aortic Regurgitation Presentation Besides CHF unique physical findings are: • Wide pulse pressure • Water-hammer (wide, bounding) pulse Quincke pulse (pulsations in nail bed)• Quincke pulse (pulsations in nail bed) • Hill sign (BP in legs as much as 40 mmHg above arm BP) • Head bobbing (de Musset sign) MTB S2CK  ‐ p. 91 35 Aortic Regurgitation Murmur • Diastolic, decrescendo murmur • Heard best: Lower left sternal border • Valsalva & Standing: Softer • Handgrip (increases afterload): Worse MTB S2CK  ‐ p. 91 Aortic Regurgitation – headphones required MTB S2CK  ‐ p. 91 Aortic Regurgitation Diagnostic tests • EKG & Chest X-ray: LVH MTB S2CK  ‐ p. 91 Aortic Regurgitation Treatment ACEi/ARBs or nifedipine: • Vasodilators • Increase forward flow of blood • Delay progression Digoxin & Diuretics: Little benefitDigoxin & Diuretics: Little benefit Surgical valve replacement: • Acute valve rupture (MI) • Replace valve before LV dilates excessively • EF < 55% • LVESD > 55 mm MTB S2CK  ‐ p. 91 Mitral Valve Prolapse (MVP) • Common • Considered normal anatomic variant • 2% to 5% of population • Particularly in women • Marfan or Ehlers-Danlos syndrome MTB S2CK  ‐ p. 91 Mitral Valve Prolapse Presentation • Most often asymptomatic When symptoms do occur: • Symptoms of CHF usually absent • Most common is: –Atypical chest pain –Palpitations –Panic attack MTB S2CK  ‐ p. 91 36 Mitral Valve Prolapse Murmur Presents with: • Midsystolic click • When severe associated with murmur • Mitral regurgitation • Valsalva & Standing worsen MVP • Squatting & Handgrip improve (diminish) MVP MTB S2CK  ‐ p. 92 Mitral Valve Prolapse – headphones required MTB S2CK  ‐ p. 92 Mitral Valve Prolapse Redundant mitral valve leaflet doesn’t seal allowing regurgitation MTB S2CK  ‐ p. 92 S ource: A ndrew P eredo Mitral Valve Prolapse Diagnostic tests • Echocardiography: Best choice • Catheterization: Rarely, if ever, done • Valve replacement: Rarely needed MTB S2CK  ‐ p. 92 Mitral Valve Prolapse Treatment Beta blockers: • When symptomatic Valve repair • With catheterWith catheter • Place clip to tighten valve • Stitches valve to tighten leaflets • Surgical repair rarely necessary • Endocarditis prophylaxis not recommended MTB S2CK  ‐ p. 92 Cardiomyopathy &  Pericardial Disease Dilated Cardiomyopathy h d hHypertrophic Cardiomyopathy Restrictive Cardiomyopathy Acute Pericarditis Pericardial Tamponade Constrictive Pericarditis 37 Cardiomyopathy/Definition • Abnormal function of heart muscle • Frequent valve or auscultory abnormalities But! It i i t f b llIt originates from an abnormally contracting or relaxing myocardium MTB S2CK  ‐ p. 92 Cardiomyopathy/Etiology • Can be dilated, hypertrophic, or restrictive • The terms “dilated cardiomyopathy”, “systolic dysfunction”, and “low EF” are often used interchangeably • Hypertrophic cardiomyopathy interchangeable with “diastolic dysfunction” Or!! “Cardiac failure with preserved EF MTB S2CK  ‐ p. 93 Cardiomyopathy/Presentation All forms give: • SOB, particularly worsened by exertion • Edema • Rales • JVD MTB S2CK  ‐ p. 93 Cardiomyopathy/Diagnostic Tests Echocardiography: • “Best initial test” • Often “Most accurate test” used EKG & Chest X-ray: • Should be performedShould be performed • Nothing specific on them confirm the diagnosis MTB S2CK  ‐ p. 93 Murmurs not increasing with expiration: • HOCM • MVP Cardiomyopathy/Treatment • All treated with diuretics • Other treatments based on type of cardiomyopathy • The only real functional difference in management and answers to questionsmanagement and answers to questions is: TREATMENT MTB S2CK  ‐ p. 93 Dilated Cardiomyopathy • In addition to previous MI and ischemia, dilated cardiomyopathy can be from: –Alcohol –Postviral myocarditis Radiation MTB S2CK  ‐ p. 93 –Radiation –Toxins (e.g., doxorubicin) –Chagas disease 38 Dilated Cardiomyopathy Dyspnea, gallop, edema, testing – same as section on CHF MTB S2CK  ‐ p. 93 Dilated Cardiomyopathy/Treatment • Multiple meds  mortality • ACEi (or ARBs) • Beta blockers (metoprolol, carvedilol) • Spironolactone (or eplerenone) Symptom Control ONLY: • Diuretics & Digoxin MTB S2CK  ‐ p. 93 Dilated Cardiomyopathy/Treatment QRS wide (> 120 ms) • Biventricular pacemaker • Improve both symptoms and survival • Automated implantable di t /d fib ill t h t litcardioverter/defibrillator has mortality benefit MTB S2CK  ‐ p. 93‐94 Hypertrophic Cardiomyopathy • HTN - MCC • MUST distinguish between hypertrophic cardiomyopathy (HCM) and HOCM HCM: Reaction to BP • Heart hypertrophies to carry loadyp p y • Develops difficulty “relaxing” in diastole • Can’t relax = Can’t receive blood • Patient becomes short of breath MTB S2CK  ‐ p. 94 Hypertrophic Obstructive Cardiomyopathy • Genetic disorder • Abnormal shape of septum • Asymmetrically hypertrophied septum and valve leaflet blocks blood leaving the heart MTB S2CK  ‐ p. 94‐95 S ou rc e: A nd re w P er ed o Hypertrophic Cardiomyopathy • S4 gallop • Fewer signs of right heart failure • Less ascites • Less enlargement of liver and spleen MTB S2CK  ‐ p. 94 39 HOCM/Presentation • Dyspnea • Chest pain • Syncope & lightheadedness • Sudden death, particularly in healthy athletes • Worsened by  heart rate – (e.g., exercise, dehydration, and diuretics) • Worsened by  in left ventricular chamber size – (e.g., ACEi, ARBs, digoxin, hydralazine, valsalva, and standing suddenly) MTB S2CK  ‐ p. 94 HOCM/Diagnostic Tests • Echo (best initial test) • Septum 1.5x thickness of posterior wall Systolic anterior motion (SAM) of mitral valve is classic for HOCM. It t ib t t b t ti Catheterization is most accurate test to determine precise gradients of pressure MTB S2CK  ‐ p. 95 contributes to obstruction. gradients of pressure across the chamber. EKG: Nonspecific ST and T wave changes are common. LVH is common. EKG can be normal in a quarter Septal Q waves in the inferior and lateral leads are common in HOCM. Hypertrophic Cardiomyopathy/Treatment Beta blockers: “Best initial therapy” both HOCM & HCM • Diuretics help HCM O• Diuretics harm HOCM MTB S2CK  ‐ p. 95 Digoxin and spironolactone are definitely always wrong in hypertrophic cardiomyopathy. HOCM/Specific Therapy Implantable defibrillator: • HOCM with syncope Ablation of septum: • Catheter placing absolute alcohol in muscle • Causes small infarctions If t i t S i l t MTB S2CK  ‐ p. 95 In HOCM, ACEi and diuretics definitely don’t help. This is the major difference between HOCM and HCM Surgical myomectomy is the therapy only if all medical and catheter procedures fail. • If symptoms persist: Surgical myomectomy Hypertrophic versus  Dilated Cardiomyopathy Hypertrophic Dilated Beta Blockers Diuretics Yes Yes Yes Yes MTB S2CK  ‐ p. 95 ACEi/ARB Spironolactone Digoxin Unclear benefit No No Yes Yes Yes Restrictive Cardiomyopathy • Combines worst aspects of dilated and hypertrophic cardiomyopathy • Heart neither contracts nor relaxes • Infiltrated with substances creating immobilityimmobility MTB S2CK  ‐ p. 96 40 Restrictive Cardiomyopathy Causes are: • Sarcoidosis • Amyloid • Hemochromatosis • Endomyocardial fibrosis • Scleroderma MTB S2CK  ‐ p. 96 Restrictive Cardiomyopathy Presentation • Dyspnea: Most common • Right heart failure • Ascites, edema, JVD • Enlargement of liver & spleen MTB S2CK  ‐ p. 96 g p • Pulmonary hypertension: Common Kussmaul sign:  jugulovenous pressure on inhalation Restrictive Cardiomyopathy Diagnosis • Echocardiography: Initial test • EF normal or elevated • EKG: Low voltage • Amyloid: Speckling of septum on echo or MTB S2CK  ‐ p. 96 cardiac MRI “Most accurate test”: Endomyocardial biopsy Rarely done Diagnosis made from biopsies elsewhere Restrictive Cardiomyopathy • Treat underlying cause • Diuretics relieve some pulmonary HTN and signs of right heart failure • No other clear therapy MTB S2CK  ‐ p. 96 Murmurs and the Effects of Maneuvers Squatting/Leg raising Standing/Valsalva Mitral and aortic  stenosis Mitral and aortic  regurgitation Increases both Increases both Decreases both Decreases both Lesion MTB S2CK  ‐ p. 96 regurgitation Mitral valve  prolapse HOCM Decrease Decrease Increase Increase Murmurs and the Effects of Maneuvers More blood increases all murmurs except MVP and HOCM. MTB S2CK  ‐ p. 96 Less blood decreases all murmurs except MVP and HOCM. 41 Effects of Maneuvers Standing from a squatting position: • Opens vessels of legs • Decreases venous return to heart Valsalva: • Exhalation against a closed glottis • Increases intrathoracic pressure • Decreases venous return to heart MTB S2CK  ‐ p. 97 Effects of Maneuvers Standing or Valsalva = Diuretic use • Stenotic & regurgitant murmurs all treated with diuretics and salt restriction St di & V l l ill i th• Standing & Valsalva will improve them MTB S2CK  ‐ p. 97 Effects of Maneuvers • MVP & HOCM: Worsen with diuretics • Diuretics decrease LV size • Diuretics worsen MVP and obstruction of HOCM St di d l l th• Standing and valsalva worsens them MTB S2CK  ‐ p. 97 Effects of Maneuvers Handgrip • Handgrip increases afterload • Contraction of arm muscles compresses arteries • Decreases emptying of heart MTB S2CK  ‐ p. 97 Decreases emptying of heart • Opposite of ACE inhibitor • Worsens AR and MR Effects of Maneuvers Amyl nitrate: • Direct arteriolar vasodilator • Decreases afterload • Simulates ACE inhibitors or ARBs on heart • Valvular disease treated with ACEi/ARB will improve with amyl nitrate MTB S2CK  ‐ p. 97 improve with amyl nitrate • Improves AR and MR • Handgrip = Fuller left ventricle • Amyl nitrate = ACEi = Emptier left ventricle Effect of Maneuvers on  Intensity (loudness) of Murmurs Handgrip Amyl nitrate Aortic stenosis Mitral stenosis A i i i Decreases No effect I Increases No effect D Lesion MTB S2CK  ‐ p. 97 Aortic regurgitation Mitral regurgitation Mitral valve prolapse HOCM Increases Increases Decreases Decreases Decreases Decreases Increases Increases 42 Effect of Maneuvers on  Intensity (loudness) of Murmurs Handgrip and amyl nitrate have no meaningful effect on mitral stenosis in the same way ACEi MTB S2CK  ‐ p. 97 stenosis, in the same way ACEi has no meaningful effect on MS Pericardial Disease • Causes of pericarditis, pericardial tamponade & constrictive pericarditis overlap • If the etiology of pericarditis extravasates fluid, then tamponade can occur • If the cause of pericarditis is chronic, fibrosis and calcification of pericardium lead to constrictive pericarditis MTB S2CK  ‐ p. 98 Pericarditis/Etiology  Any… • Infection • Inflammatory disorder • Connective tissue disorder • Chest trauma or cancer near the heartChest trauma or cancer near the heart …can cause pericarditis • Most common infection is viral MTB S2CK  ‐ p. 98 Pericarditis/Etiology  Systemic lupus erythematosus: Most common connective tissue disorder But… • Wegener granulomatosis • Goodpasture syndrome • Rheumatoid arthritis • Polyarteritis nodosa and others …can cause pericarditis MTB S2CK  ‐ p. 98 Pericarditis/Presentation “What Is the Most Likely Diagnosis?” • Sharp chest pain • Changes with respiration • Changes with position of body Worsened by lying flat• Worsened by lying flat • Improved by sitting up MTB S2CK  ‐ p. 98 Pericarditis/Diagnostic Tests • EKG shows ST segment elevation in all leads, but the most specific finding is PR segment depression MTB S2CK  ‐ p. 98‐99 43 Pericarditis/Treatment • Treat cause • Majority: Idiopathic –“Idiopathic” presumed viral –Coxsackie B virus T t d ith NSAID ( ib f• Treated with NSAIDs (e.g., ibuprofen, naproxen) • Colchisine -  recurrences MTB S2CK  ‐ p. 99 Pericardial Tamponade/Etiology • Any cause of pericarditis can extravasate enough fluid to cause tamponade • Compression heart starts on right side • Walls are thinner • 50 mL acutely cause tamponadey p • Over weeks to months, pericardium stretches for 2 L of fluid • Can also be from trauma • Bleed requires emergent thoracotomy MTB S2CK  ‐ p. 99 Pericardial Tamponade/Presentation “What Is the Most Likely Diagnosis?” • Hypotension • Tachycardia • Distended neck veins • Clear lungsClear lungs MTB S2CK  ‐ p. 99 Which of the following physical findings is most likely to be associated with this patient? • Pulsus paradoxus • Decrease of more than 10 mmHg in systolic blood pressure on inhalation Pericardial Tamponade MTB S2CK  ‐ p. 100 Pericardial Tamponade EKG: • Electrical alternans (different heights of QRS complexes between beats) MTB S2CK  ‐ p. 100 Pericardial Tamponade Chest X-ray: • Enlarged cardiac shadow expanding in both directions (“globular heart”) Echocardiogram: • Right atrial and ventricular diastolic collapse Right heart catheterization: Equalization of pressures in diastole MTB S2CK  ‐ p. 100‐101 44 78-year-old man with lung cancer experiences several days of increasing SOB. He’s lightheaded today. BP 106/70; pulse 112; JVD present; lungs: clear, BP drops to 92/58 on inhalation. Which is most appropriate to confirm the diagnosis? a. EKG b Chest X-ray Normal acutely; “globular heart” later Low voltage non-specific. Rare alternans b. Chest X ray c. Echocardiogram d. Right heart catheterization e. Cardiac MRI MTB S2CK  ‐ p. 100 y; g Most accurate; should do echo first Not clearly right for ANYTHING at this time  Pericardial Tamponade Treatment • Pericardiocentesis • Needle rapidly reexpands the heart • IV fluids • A hole or “window” recurrent cases MTB S2CK  ‐ p. 101 Diuretics will decrease intracardiac filling pressure and may markedly worsen collapse of right side of heart Constrictive Disease • Any cause of pericarditis with calcification and fibrosis • Prevents filling of right side of heart • Tuberculosis MTB S2CK  ‐ p. 101 Constrictive Disease “What Is the Most Likely Diagnosis?” • Signs of right heart failure such as: – Edema – Ascites – Enlargement of liver and spleen – JVD • Constrictive pericarditis is a combination of physical findings described above with calcification on chest X-ray MTB S2CK  ‐ p. 101 Constrictive Disease “Which physical findings is most likely associated with this patient?” Kussmaul sign: • Increase in JVD on inhalation • Normally neck veins go down on inhalationNormally neck veins go down on inhalation “Knock”: • Extra heart sound in diastole • From ventricular filling • Heart fills to its maximum, it hits the stiff, rigid pericardium with a “knock” MTB S2CK  ‐ p. 101 Pericardial Knock – headphones required 45 Constrictive Disease “Best initial test” • Chest X-ray: Calcification & fibrosis MTB S2CK  ‐ p. 101 Commons.wikimedia.org. Used with permission Constrictive Disease • CT scan or MRI more accurate, not 1st • Echocardiogram: Excludes RV hypertrophy or cardiomyopathy as cause • Myocardium moves normally with• Myocardium moves normally with constrictive pericarditis MTB S2CK  ‐ p. 101 Constrictive Disease Treatment Diuretics: • Decompress filling of heart • Relieves edema and organomegaly Surgical removal of pericardium MTB S2CK  ‐ p. 101 Peripheral Artery Disease, Aortic  Disease, & Heart Disease  in Pregnancy Definition Etiology Presentation Diagnosis Treatment  Peripheral Artery Disease (PAD)/Etiology Stenosis of peripheral arteries from: • Diabetes mellitus • Hyperlipidemia • Hypertension • Tobacco smokingTobacco smoking Same causes as Coronary Disease!! MTB S2CK  ‐ p. 102 Peripheral Artery Disease/Presentation “What Is the Most Likely Diagnosis?” • Pain in calves on exertion • Relieved by rest • Walking up or down hills • Severe disease causes loss of: H i f lli l– Hair follicles – Sweat glands – Sebaceous glands • The skin becomes smooth and shiny MTB S2CK  ‐ p. 102 Spinal stenosis pain is worse when walking down hills because of leaning back 46 Peripheral Artery Disease Diagnostic tests • “Best initial test” = Ankle-brachial index (ABI) • ABI: Ratio of BP in ankles to brachial arteries • Normally equal or slightly greater in ankles because of gravity • If difference between them is > 10% (ABI < 0 9)• If difference between them is > 10% (ABI < 0.9), disease is present • “Most accurate test” = angiogram • Angiogram not necessary unless revascularization will be done MTB S2CK  ‐ p. 102 There is no routine screening for PAD since there is no mortality benefit to be obtained Peripheral Artery Disease Treatment • The best initial therapy is: – Aspirin – Smoking cessation – Cilostazol • Single most effective medication: CilostazolSingle most effective medication: Cilostazol • Surgery or angioplasty if medical therapy not effective MTB S2CK  ‐ p. 102‐103 In all major vascular disease control the following: • BP • LDL < 100 • Diabetes 67-year-old man in ED with sudden onset chest pain is also felt between his scapulae. He has a history of HTN and tobacco smoking. BP 169/108. What is the best initial test? a. Chest X-ray b. Chest CT c. MRA d. Transesophageal echocardiogram e. Transthoracic echocardiogram f. CT angiogram g. Angiography MTB S2CK  ‐ p. 103 Don’t show specific changes MRA, TEE, and CTA have same accuracy; not “most accurate”, neither best initial Most accurate, but not best initial test Aortic Dissection Author: J. Heuser; commons.wikimedia.org Used with permission Aortic Disease Most frequently tested points in aortic disease • Diagnosis & treatment of acute dissection • Screening recommendations MTB S2CK  ‐ p. 103 Key points for presence of aortic dissection • Pain in between the scapulae • Difference in blood pressure between the arms Aortic Disease/Treatment • For dissection, “Most important step” is: Control BP • This can be done with: – Beta blockers – Nitroprusside • Beta blockade decreases “shearing forces” that worsens dissectionworsens dissection • Beta blockers must start before nitroprusside to protect against reflex tachycardia of nitroprusside, which worsens shearing forces MTB S2CK  ‐ p. 104 47 Which of the following is the most appropriate screening for aortic aneurysm? a. Everyone > 50 with CT angiography b. Men who ever smoked > 65 with ultrasound c. Everyone > 50 with ultrasound d Everyone > 65 with ultrasound  d. Everyone > 65 with ultrasound e. Men > 65 with ultrasound MTB S2CK  ‐ p. 104 Incidence of AAA is less in both nonsmokers and in women, so there is no recommendation for screening in those groups Abdominal Aortic Aneurysm Which of the following is most dangerous to a pregnant woman? a. Mitral stenosis b. Peripartum cardiomyopathy Ei h Choose this if peripartum  c. Eisenmenger phenomenon d. Mitral valve prolapse e. Atrial septal defect MTB S2CK  ‐ p. 104 p p cardiomyopathy is not one of the choices Not as dangerous as choices “b” and “c” Peripartum Cardiomyopathy • Unknown why antibodies are made against the myocardium in some pregnant women • LV dysfunction often reversible and short termshort term • If LV dysfunction does not improve, then must undergo cardiac transplantation MTB S2CK  ‐ p. 105 Peripartum Cardiomyopathy • Therapy the same as for dilated cardiomyopathy of any cause: – ACEi/ARB – Beta blockers – Spironolactone – Diuretics – Digoxin • Repeat pregnancy with peripartum cardiomyopathy will kill 50-70% of women!! MTB S2CK  ‐ p. 105 Peripartum cardiomyopathy develops after delivery in most cases; ACEi/ARBs must be used Eisenmenger Syndrome • From right-to-left shunt from pulmonary HTN • Develops in person with ventricular septal defect with left-to-right shunt that eventually develops pulmonary HTN • When pulmonary HTN becomes very severe shunt reverses • Right-to-left shunting develops MTB S2CK  ‐ p. 105 48 Eisenmenger Syndrome If peripartum cardiomyopathy is not one of the choices in asking, “What is the worst cardiac disease in pregnant women?” then • Look for Eisenmenger in the choices MTB S2CK  ‐ p. 105 • Pregnancy increases plasma volume by 50%. • Mitral stenosis will worsen in pregnancy, • But not as much as peripartum cardiomyopathy or Eisenmenger Eisenmenger Syndrome P l HTN Large left-to-right shunt (congenital heart defect) Pulmonary HTN Reverse of the shunt: right-to-left shunt MTB S2CK  ‐ p. 105 1 Dermatology – Part 1 Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Dermatology – Part 1 Cutaneous Malignancies Atopic Dermatitis (Eczema) Psoriasis Pityriasis Rosea Seborrheic Dermatitis (Dandruff) Blistering Diseases Cutaneous malignancies • Greater with pale skin • More sun-exposed areas • Diagnosis: Biopsy • Treatment: Surgical removal • No truly effective chemotherapyNo truly effective chemotherapy MTB S2CK  ‐ p.  363 Skin Cancer • More sun, more cancer • Biopsy • Remove Malignant Melanoma • More frequent in sun-exposed areas But! • Not exclusive to those areas Benign vs. Malignant Melanoma clinically – ABCDE: • A: Asymmetry • B: Border irregularity • C: Color irregularities • D: Diameter > 6 mm • E: Evolution (changing over time) MTB S2CK  ‐ p. 363 Malignant Melanoma • Diagnosis? • Suspicious? Biopsy! • Include entire thickness of lesion if iblpossible MTB S2CK  ‐ p.  363 Worst prognosis!! Growing lesions Distinction Between Benign and Malignant   Benign Malignant Round  Even borders  Asymmetric Borders uneven  MTB S2CK  ‐ p. 364 Color evenly spread Diameter constant  Color uneven  Diameter increases 2 Benign Lesion MTB S2CK  ‐ p. 364 Source: Andrew Peredo Malignant Melanoma  Diagnostic Test • Full thickness biopsy: indispensible • Don’t perform shave biopsy Treatment/Prognosis • Surgical removalSurgical removal • Must include normal skin surrounding lesion • Interferon injection helpful in widespread disease • Melanoma has strong tendency to metastasize to brain MTB S2CK  ‐ p. 364 Squamous Cell Cancer • Sunlight • Organ transplant!!!! • Immunosuppressive drugs! • Squamous starts looking like ulcer • Doesn’t heal, grows • Biopsy and remove MTB S2CK  ‐ p. 364 Squamous Cell Cancer MTB S2CK  ‐ p. 364 Source: James Heilman MD Basal Cell Carcinoma • Most common skin cancer • Question describes: • “Waxy lesion” • “Shiny like a pearl” U lik l id i t• Unlike melanoma, wide margins not necessary • Shave biopsy fine! (diagnostic) • Recurrence < 5% • Basal cell: use Mohs microsurgery MTB S2CK  ‐ p. 364 Basal Cell Carcinoma MTB S2CK  ‐ p. 364 3 Basal Cell Carcinoma/ Mohs Micrographic Surgery • Remove skin cancer under dissecting microscope • Very thin slices of skin • Immediate frozen sectionImmediate frozen section • VERY precise way to treat skin cancer • Mohs: –Remove cancer –Keep normal MTB S2CK  ‐ p. 365 Basal Cell Carcinoma/ Mohs Micrographic Surgery • Stop resecting when margin is cancer- free • No removal of wide margins MTB S2CK  ‐ p. 365 Mohs Best: • Delicate areas • Eyelid & Ear Kaposi Sarcoma (KS) • In past, KS seen only in older men of Mediterranean origin • Now: AIDS • From HHV-8, which is oncogenic R ddi h/ li h• Reddish/purplish • More vascular than others MTB S2CK  ‐ p. 365 Kaposi Sarcoma (KS) MTB S2CK  ‐ p. 365 Kaposi Sarcoma (KS) • Also in GI tract and lung • Only from AIDS via sexual contact associated with KS • IDU AIDS rarely associated with KS MTB S2CK  ‐ p. 365 Kaposi Sarcoma/Treatment • Unlike other skin cancers, KS not routinely removed surgically 1. Treat AIDS with antiretrovirals 2. Majority disappear as CD4 improves 3 I t l i l i j ti f i i ti3. Intralesional injections of vincristine or interferon 4. If these fail, use chemotherapy with liposomal doxorubicin MTB S2CK  ‐ p. 366 4 Actinic Keratoses • Premalignant • From high-intensity sun exposure in fair- skinned people • Very small risk of SCC for each individual lesionindividual lesion MTB S2CK  ‐ p. 366 Actinic Keratoses MTB S2CK  ‐ p. 366 © Richard Usatine, M.D. Used with permission. Actinic Keratoses MTB S2CK  ‐ p. 366 © Richard Usatine, M.D. Used with permission. Actinic Keratoses • Many occur in a single person • Risk is cumulative • Like cervical dysplasia and cervical cancer • Slow to progress • Remove with:Remove with: – Curettage – Cryotherapy – Laser – Topical 5-fluorouracil – Imiquimod MTB S2CK  ‐ p. 366 Actinic Keratoses Imiquimod • Local immunostimulant • Also for molluscum contagiosum • Condyloma acuminatum MTB S2CK  ‐ p. 366 Seborrheic Keratoses • Extremely common in elderly • Hyperpigmented lesions • Commonly referred to as “liver spots” • “Stuck on” appearance • May look like melanoma to some people • Seborrheic keratoses = Zero malignant potential MTB S2CK  ‐ p. 366 5 Seborrheic Keratoses Removed with: • Cryotherapy • Surgery • Laser • Removal (cosmetic reasons) MTB S2CK  ‐ p. 366 Seborrheic Keratoses MTB S2CK  ‐ p. 366 Source: James Heilman MD Atopic Dermatitis (Eczema) • Common skin disorder • Associated with overactivity of mast cells & immune system Look for history of: • Asthma • Allergic rhinitis • Family history of atopic disorders • Onset < age 5, very rare to start > 30 MTB S2CK  ‐ p. 366 Atopic Dermatitis (Eczema)/Presentation • From premature and idiosyncratic release of transmitters (e.g., histamine) • Pruritus & scratching is most common presentation • Scratching leads to scaly rough areas ofScratching leads to scaly rough areas of thickened skin • On face, neck & skin folds • Popliteal area behind knee MTB S2CK  ‐ p. 366 Atopic Dermatitis (Eczema)/Presentation MTB S2CK  ‐ p. 366 © Richard Usatine, M.D. Used with permission. Atopic Dermatitis (Eczema)/Presentation MTB S2CK  ‐ p. 366 © Richard Usatine, M.D. Used with permission. 6 Atopic Dermatitis (Eczema)/Presentation • Itching  scratching • Scratching  more itching • Superficial skin infections from Staphylococcus are common • Microorganisms driven under epidermis by scratchingscratching • This, in turn,  more itching MTB S2CK  ‐ p. 367 Food allergies don’t exacerbate atopic dermatitis Skin thickened because of scratching and drying = lichenified Atopic Dermatitis (Eczema)/Skin Care 1. Stay moisturized: dry skin is more itchy 2. Use a humidifier, especially in winter 3. Avoid bathing, soap, and washcloths (skin hyperirritable) 4. Avoid brushes, washcloths, hot water, and , , , anything that rubs on skin 5. Cotton less irritating than wool MTB S2CK  ‐ p. 367 IgE levels: Elevated in atopic dermatitis Atopic Dermatitis (Eczema)/Medical Therapy 1. Topical corticosteroids: used in flares of disease (oral steroids only in most severe acute flares) 2. Tacrolimus and pimecrolimus • T cell–inhibiting agents L t t l• Longer-term control • Help get patient off steroids • Used systemically in organ transplant recipients • Prevent organ rejection • Used topically for atopic dermatitis MTB S2CK  ‐ p. 367 Atopic Dermatitis (Eczema)/Medical Therapy 3. Antihistamines: • Mild disease: nonsedating drugs (cetirizine, fexofenadine, loratadine) • Severe disease: hydroxyzine, diphenhydramine, doxepine 4. Antibiotics (e.g., cephalexin, mupirocin, retapamulin) when impetigo occurs 5. UV light (phototherapy) for severe recalcitrant disease MTB S2CK  ‐ p. 367 Psoriasis/Definition/Presentation • Incredibly common • 2 million in US • Characterized by silvery, scaly plaques • Not itchy most of the time • Arthritis < 10% • Extensive disease associated with depression MTB S2CK  ‐ p. 367 Psoriasis/Definition/Presentation MTB S2CK  ‐ p. 368 7 Psoriasis/Treatment Local Disease 1.Topical high-potency steroids: fluocinonide, amcinolone, betamethasone, clobetasol 2.Vitamin A & Vitamin D ointment • Helps get patient off steroids • Vitamin D agent is calcipotriene • Steroids cause skin atrophy 3. Coal tar preparation 4.Pimecrolimus and tacrolimus • Used in delicate areas (e.g., face & penis) • Alternative to steroids • Less deforming MTB S2CK  ‐ p. 368 Psoriasis/Treatment Steroids cause atrophy • Inhibit collagen formation and growth • Convert AAs  glucose • Gluconeogenesis MTB S2CK  ‐ p. 368 Gluconeogenesis Psoriasis/Treatment Extensive Disease 1.UV light 2.Antitumor necrosis factor (TNF) inhibitors • Etanercept • Adalimumab • Infliximab • Miraculous for severe disease 3.Methotrexate: • Last because of effects on liver & lung • First for psoriatic arthritis MTB S2CK  ‐ p. 368 TNF inhibitors reactivate TB • Screen with PPD prior to use MTB S2CK  ‐ p. 368 Pityriasis Rosea • Idiopathic, transient dermatitis • Starts with a single lesion (herald patch) • Then disseminates • Can look like secondary syphilis • But spares palms & soles • Transient • If symptomatic: treat with steroids or UV light MTB S2CK  ‐ p. 368 Pityriasis Rosea MTB S2CK  ‐ p. 369 Source: Andrew Peredo 8 Seborrheic Dermatitis (Dandruff) • Hypersensitivity reaction • Dermal infection • Noninvasive dermatophyte organisms • Both topical steroids and antifungal t ( k t l ) f lagents (e.g., ketoconazole) are useful MTB S2CK  ‐ p. 369 Seborrheic Dermatitis (Dandruff) Increased in: • AIDS • Parkinson’s disease “Seborrheic” = Benign MTB S2CK  ‐ p. 369 Pemphigus Vulgaris • Both idiopathic/autoimmune form and • Drug induced form Associated with: • ACE inhibitors • Penicillamine • Phenobarbital • Penicillin MTB S2CK  ‐ p. 369 Pemphigus Vulgaris Autoantibodies split epidermis, resulting in: • Bullae that easily rupture • Thin-walled I l t f th• Involvement of mouth • Fluid loss & infection • Widespread (acts like burn) MTB S2CK  ‐ p. 369 Pemphigus Vulgaris Source: phil.cdc.gov Pemphigus Vulgaris Source: commons.wikimedia.org 9 Pemphigus Vulgaris • Characteristic finding: “Nikolsky sign” • Loss or “denuding” of skin from mild pressure Nikolsky sign:y g • Removal of superficial layer of skin • Single sheet while pulling on it • Finger’s worth of pressure MTB S2CK - p. 370 Pemphigus Vulgaris • “Most accurate test” = biopsy • Biopsy shows: autoantibodies on immunofluorescent (IF) studies MTB S2CK  ‐ p. 370 Without treatment, pemphigus is fatal Pemphigus Vulgaris/Treatment 1. Systemic steroids (prednisone) 2. Azathioprine or mycophenolate to wean patient off steroids 3. Rituximab (anti-CD20 antibodies) or IVIG in refractory casesin refractory cases MTB S2CK  ‐ p. 370 Bullous Pemphigoid Much milder than pemphigus: • Bullae stay intact • Less loss of fluid • Less infection • Mouth involvement uncommon MTB S2CK  ‐ p. 370 Bullous Pemphigoid © Richard Usatine, M.D. Used with permission. Bullous Pemphigoid • Biopsy with IF stains is “Most accurate test” • “Best initial therapy”: Prednisone • To get patients off steroids, use azathioprine, cyclophosphamide, or mycophenolate • Mild bullous pemphigoid responds to p p g p erythromycin, dapsone, and nicotinamide (not niacin) MTB S2CK  ‐ p. 370 Nikolsky sign absent in bullous pemphigoid 10 Porphyria Cutanea Tarda Blistering skin disease Sun-exposed areas With history of: • Liver disease • Hepatitis C • Alcoholism • Estrogen use • Iron overload (hemochromatosis) MTB S2CK  ‐ p. 370 Porphyria Cutanea Tarda Hepatitis C: • Most frequently tested association with PCT MTB S2CK  ‐ p. 370 Look for involvement of: backs of hands & face Porphyria Cutanea Tarda/  Diagnostic Tests/Treatment “Most accurate test” • Increased uroporphyrins on 24-hr urine • Deficiency of uroporphyrin decarboxylase activity TreatmentTreatment • Correct underlying cause • Stop alcohol • Stop estrogens • Remove iron with phlebotomy MTB S2CK  ‐ p. 370 Dermatology – Part 2 Skin Infections Drug Reactions Staphylococcal Scalded Skin Syndrome and  Toxic Shock Syndrome  Acne Impetigo • Most superficial bacterial skin infection • Staphylococcus and Streptococcus invade epidermis • Results in weeping, crusting, oozing, & draining of skindraining of skin MTB S2CK  ‐ p. 371 Impetigo/Treatment Mild disease with topical agents: • Mupirocin • Bacitracin • Retapamulin Severe disease with oral agents: • Dicloxacillin or cephalexin Community-acquired MRSA with: • Doxycycline • Clindamycin • Trimethoprim/sulfamethoxazole (TMP/SMZ) MTB S2CK  ‐ p. 371 11 Erysipelas • Much more severe than impetigo • Occurs at deeper level in skin • Streptococcus > Staphylococcus • Invades dermal lymphatics • Causes bacteremia leukocytosis fever andCauses bacteremia, leukocytosis, fever, and chills • Fatal, if untreated MTB S2CK  ‐ p. 371 Skin infections can cause glomerulonephritis, but not rheumatic fever. Erysipelas/Presentation • Bright, red, hot swollen • Lesion on face • Leukocytosis • Often systemic disease MTB S2CK  ‐ p. 371 Erysipelas/Presentation Source: Thomas F Sellers Erysipelas/Treatment • Although erysipelas is more often from Streptococci, you must treat for Staphylococcus as well unless you have a definitive diagnostic test such as blood cultures. Treatment of all skin infections is similar • Same answers as for: – Cellulitis – Folliculitis – Furuncles – Carbuncles MTB S2CK  ‐ p. 371 Erysipelas/Treatment Mild disease - oral medications: • Dicloxacillin, cephalexin, cefadroxyl • Penicillin allergic: erythromycin, clarithromycin, or clindamycin MRSA: Doxycycline, clindamycin, or TMP/SMX MTB S2CK  ‐ p. 372 Erysipelas/Treatment Severe disease (e.g., fever): IV medications: • Oxacillin, nafcillin, cefazolin Penicillin allergic: Clindamycin, vancomycin MRSA:MRSA: • Vancomycin, linezolid, daptomycin, tigecycline, ceftaroline MTB S2CK  ‐ p. 372 Cross reaction Between penicillin and cephalosporins unusual (< 5%) 12 Erysipelas/Treatment Step 2 CK tests: Route of administration (O l I t ) MTB S2CK  ‐ p. 372 (Oral vs Intravenous) Cellulitis • Soft tissue infection of skin • Extends from dermis into subcutaneous tissue • Skin: Warm, red, swollen, and tender MTB S2CK  ‐ p. 372 Cellulitis MTB S2CK  ‐ p. 372 Cellulitis • Involves legs > arms • Doesn’t have collections of walled-off infection, which is an abscess • Cellulitis isn’t only at hair follicle; that's folliculitis, furuncles, and carbuncles MTB S2CK  ‐ p. 372 Skin infection: Caused by S. aureus NOT S. epidermidis S. epidermidis lives on skin as normal flora Cellulitis/Diagnostic Tests • No diagnostic testing needed • “Most accurate test” –Inject sterile saline into skin & aspirate for culture • Yield only 20%• Yield only 20% • Staphylococcus > Streptococcus MTB S2CK  ‐ p. 372 Cellulitis/Treatment • Same as for erysipelas • Topical antibiotics will not cover cellulitis • Below dermal/epidermal junction T i l tibi ti ’t h• Topical antibiotics won’t reach MTB S2CK  ‐ p. 372 13 Folliculitis, Furuncles, Carbuncles • Originate around hair follicles • Different terms don’t have precise definitions • Indistinguishable, no cutoff in size MTB S2CK  ‐ p. 372 Severe disease = fever, chills, bacteremia Folliculitis, Furuncles, Carbuncles/ Size of the Infection • Folliculitis: Earliest & mildest • Furuncle: Small abscess or collection of infected material • Carbuncle: Collection of furuncles Folliculitis < Furuncle < Carbuncle Treat: Ox/Clox/Diclox/Naf MTB S2CK  ‐ p. 372 Folliculitis, Furuncles, Carbuncles Source: cdc.gov Folliculitis, Furuncles, Carbuncles Source: commons.wikimedia.org Folliculitis, Furuncles, Carbuncles MTB S2CK  ‐ p. 373 Folliculitis, Furuncles, Carbuncles/ Penicillin Allergy Reaction - Rash • Use cephalosporins Reaction - Anaphylaxis • Mild infection: Macrolides, clindamycin, doxycycline, or TMP/SMZ • Severe infection: Vancomycin, linezolid, daptomycin, or tigecycline MTB S2CK  ‐ p. 373 14 Folliculitis, Furuncles, Carbuncles/ Other Antistaphylococcal Medications • Beta-lactam/beta-lactamase combinations – Amoxicillin/clavulanate – Ticarcillin/clavulanate – Ampicillin/sulbactam – Piperacillin/tazobactam • Carbapenems (imipenem, meropenem) MTB S2CK  ‐ p. 373‐374 Fungal Infections • Dermatophyte = superficial fungal infection = tinea For example: • Tinea corporis = bodyp y • Tinea manum = hand • Tinea pedis = foot • Tinea cruris = groin (“jock itch”) MTB S2CK  ‐ p. 374 Fungal Infections © Richard Usatine, M.D. Used with permission. Fungal Infections/Diagnostic Tests/Treatment “Best initial test” • KOH (potassium hydroxide) • Dissolves epidermal skin cells • Leaves fungi intact “Most accurate test” • Fungal culture MTB S2CK  ‐ p. 374 Fungal Infections/Diagnostic Tests/Treatment “Best initial therapy” • Topical antifungal agent if no hair or nails involved • For hair (tinea capitis) and nail (tinea unguium)unguium) –Terbinafine –Itraconazole MTB S2CK  ‐ p. 374 Fungal Infections/Treatment Topical antifungal agents: • Clotrimazole • Ketoconazole • Econazole Mi l Oral ketoconazole causes gynecomastia• Miconazole • Nystatin • Ciclopirox MTB S2CK  ‐ p. 375 causes gynecomastia 15 Fungal Infections/Oral and Vaginal Candidiasis • Same answers for both • KOH: Best initial test • Fungal culture: Most accurate test • With clear presentation: Treat • Topical antifungal from previous list MTB S2CK  ‐ p. 375 Drug Reactions • Hypersensitivity reactions to medications vary in severity • When severity of reaction changes, the name of reaction changes Drugs causing hypersensitivity reactions: • Penicillins • Sulfa drugs (including thiazides, furosemide, and sulfonylureas) • Allopurinol • Phenytoin • Lamotrigine • NSAIDs MTB S2CK  ‐ p. 375 Drug Reactions Drugs that cause hypersensitivity reactions of the skin are the same that cause: • Hemolysis I t titi l h iti MTB S2CK  ‐ p. 375 • Interstitial nephritis • Thrombocytopenia Morbilliform Rash  • Mildest reaction • Skin stays intact • No mucous membrane involvement • No specific therapy MTB S2CK  ‐ p. 375 Morbilliform Rash  MTB S2CK  ‐ p. 376 Source: commons.wikimedia.org Erythema Multiforme  • Widespread • “Target” lesions • Mostly on trunk • Mucous membrane uninvolved • From herpes or mycoplasma • Prednisone may benefit MTB S2CK  ‐ p. 375 16 Erythema Multiforme  Erythema multiforme is characterized by multiple small target-shaped l i th t b MTB S2CK  ‐ p. 375 lesions that can be confluent Source: Andrew Peredo Stevens‐Johnson Syndrome • Very severe • Involves mucous membranes • Sloughs off respiratory epithelium • May lead to respiratory failure • Steroids not beneficial • Use intravenous immunoglobulins (IVIG) MTB S2CK  ‐ p. 375 Toxic Epidermal Necrolysis • Mucous membrane involvement • Nikolsky sign • Steroids definitely don’t help • Treat with IVIG MTB S2CK  ‐ p. 375 Toxic Epidermal Necrolysis The skin comes off in a sheet, simulating a burn. MTB S2CK  ‐ p. 376 Source: Conrad Fischer, MD Staphylococcal Scalded Skin Syndrome (SSSS)  and Toxic Shock Syndrome (TSS) • Different severities of same event • Reaction to toxin in surface of Staphylococcus • SSSS looks similar to TEN, including Nikolsky sign • TSS has skin involvement as well as life-TSS has skin involvement as well as life threatening multi-organ involvement: – Hypotension – Renal dysfunction ( BUN and creatinine) – Liver dysfunction – CNS involvement (delirium) MTB S2CK  ‐ p. 377 Staphylococcal Scalded Skin Syndrome and  Toxic Shock Syndrome Both treated with: Antistaphylococcal medications • Oxacillin or nafcillin are most effective • Cefazolin is essentially equal • Antibiotics don’t reverse disease • Kills Staphylococcus that produces toxin MTB S2CK  ‐ p. 377 17 Acne/Treatment Mild acne • Topical antibacterials: Benzoyl peroxide • If ineffective add topical antibiotics (e.g., clindamycin or erythromycin) MTB S2CK  ‐ p. 377 Acne/Treatment Moderate acne • Add topical vitamin A derivatives: tretinoin, adapalene, or tazarotene to topical antibiotics • If no response to topical vitamin A• If no response to topical vitamin A derivatives and antibiotics, use oral antibiotics (e.g., minocycline or doxycycline) MTB S2CK  ‐ p. 377 Acne/Treatment Severe acne • Add oral vitamin A, isotretinoin to oral antibiotics • Isotretinoin causes hyperlipidemia MTB S2CK  ‐ p. 377 Vitamin A derivatives extremely teratogenic 1 EMERGENCY MEDICINE Niket Sonpal, MD Chief Resident Lenox Hill Hospital‐NSLIJ Assistant Clinical Professor ‐ Touro College of Medicine Toxicology, Poisoning, & Overdose 32-year-old woman with a history of depression comes to ED 30 minutes after taking a bottle of pills in a suicide attempt. BP 118/70, pulse 90, and respirations normal. She refuses to tell you what she took. What is the next step? a. Induce emesis with ipecac It could be caustic and injure on thpb. Gastric lavagec. Psychiatric consultation d. Serum chemistry e. Urine toxicology screen f. Cathartics/laxatives g. Whole bowel irrigation h. Naloxone i. Flumazenil MTB S2CK  ‐ p. 533  Pills will not make that transit time the way up Consultations are 99% wrong on USMLE Takes too long Urine won’t show up yet We don’t know if it’s benzos We don’t know if it’s opiates Doesn’t change outcomes Treatment of Overdose Gastric Lavage OVERDOSE TREATMENTS Cathartics MTB S2CK  ‐ p. 534 Ipecac Fluids and Diuresis Bowel Irrigation Initial Management of Poisoning Gastrointestinal Emptying • Gastric lavage Gastric emptying of any kind is always wrong with… MTB S2CK  ‐ p. 534 • Caustics (acids and alkali) • Altered mental status Initial Management of Poisoning Gastric lavage is rarely done. • Removes 50% of pills at 1 hour • Removes 15% of pills at 2 hours • Ipecac is always a wrong answer in ED MTB S2CK  ‐ p. 534 2 Initial Management of Poisoning Ipecac • No inpatient benefit • 15-20 minutes onset • Hinders antidotes MTB S2CK  ‐ p. 534 Initial Management of Poisoning Cathartics • Cathartic agents – WRONG answer • Prokinetics – WRONG answer MTB S2CK  ‐ p. 534 Initial Management of Poisoning Forced Diuresis • Fluids and diuretics is always a wrong answer • Risk of PE > benefit MTB S2CK  ‐ p. 534 Initial Management of Poisoning Whole Bowel Irrigation • NGT with polyethylene glycol-electrolyte solution is almost always wrong • Only for: Iron ingestion– Iron ingestion – Lithium – Drug-filled packets MTB S2CK  ‐ p. 534 Initial Management of Poisoning • When answer is unclear and cause of overdose is asked say: – Acetaminophen 1st Most Common – Aspirin 2nd Most Common • What to do is often unclear. What is useless or dangerous (ipecac, forced diuresis, cathartics) is very clear. MTB S2CK  ‐ p. 535 Woman comes to ED one hour after taking a bottle of pills. BP 118/70, pulse 90/min, and respirations 14/min. She is confused, disoriented, and lethargic. What is the next step in the management? a. Flumazenil Seizure risk too high 2nd line b. Gastric lavage c. Psychiatric consultation d. Naloxone and dextrose e. Intubation MTB S2CK  ‐ p. 535  Dangerous in AMS Never get a consult you’re an MD Not the first step 3 Initial Management of Poisoning Psychiatric consultation is indicated for suicide attempt, but is a wrong answer on USMLE S2 MTB S2CK  ‐ p. 535 is a wrong answer on USMLE S2 CK when specific antidotes and diagnostic tests are needed. Initial Management of Poisoning Opiate overdose is fatal: • Give naloxone immediately Benzodiazepine overdose by MTB S2CK  ‐ p. 535 Benzodiazepine overdose by itself is not fatal and acute withdrawal causes seizures • Don’t give flumazenil Initial Management of Poisoning Charcoal • Charcoal is benign • Charcoal is not dangerous • Charcoal is superior to lavage and iipecac MTB S2CK  ‐ p. 535‐536 When you don’t know what to do in toxicology, give charcoal Acetaminophen • Legal drugs kill more people in the United States than illegal drugs because they’re less expensive and more available • Toxicity of acetaminophen with ingestion > 8 to 10 g • Fatality with ingestions > 12 to 15 g MTB S2CK  ‐ p. 536 Acetaminophen Four Most Common Acetaminophen Overdose Questions: 1. If a clearly toxic amount of acetaminophen has been ingested (> 8–10 g) Ans er N acet lc steineAnswer: N-acetylcysteine 2. If the overdose was > 24 hours ago No therapy MTB S2CK  ‐ p. 536 Acetaminophen 3. Amount of ingestion unclear? Drug level 4. Charcoal does not make N-acetylcysteine ineffective Charcoal isn’t contraindicated with N- acetylcysteine MTB S2CK  ‐ p. 536 4 Aspirin Overdose • “ What is the most likely diagnosis?” Renal Toxicity Aspirin Overdose Altered Mental Tinnitus MTB S2CK  ‐ p. 536 Respiratory Alkalosis  Metabolic AcidosisHyperventilation Mental Status Increased Anion Gap Aspirin Overdose • Aspirin causes diffuse, multisystem toxicity Increased PT ARDS MTB S2CK  ‐ p. 536 Lactic Acidosis Aspirin Overdose Increased PTT Respiratory Failure Aspirin Overdose • Treatment is alkalinizing urine, which increases rate of aspirin excretion • Know blood gas in aspirin overdose MTB S2CK  ‐ p. 536 Tinnitus, respiratory alkalosis, and metabolic acidosis are the key to diagnosing aspirin overdose. Which of the following is most likely to be found in aspirin overdose? (Normal values: pH 7.40, pCO2 40, HCO3 24) a. pH 7.55 pCO2 50 HCO3 24 b. pH 7.25 pCO2 62 HCO3 38 This is a distracter Aspirin overdose never givesp p 2 3 c. pH 7.46 pCO2 22 HCO3 16 d. pH 7.35 pCO2 32 HCO3 20 MTB S2CK  ‐ p. 536‐537  p grespiratory acidosis Metabolic acidosis with respiratory compensation Depressed patient presents with altered mental status from ingesting multiple toxic substances. You know for certain that he took some lorazepam only today, for the first time. There is no response to naloxone or dextrose. The patient is given flumazenil and immediately seizes. What is the most likely cause of the seizure? a. Cocaine withdrawal b. Opiate withdrawal c. Tricyclic antidepressants d. SSRIs e. Aspirin MTB S2CK  ‐ p. 537  Causes tinnitus and hyperventilation, not seizures Doesn’t cause seizures Cocaine toxicity causes seizures, not withdrawal SSRIs toxicity causes serotonin syndrome (SS) What is the best initial test for the patient previously described? a. Urine toxicology b. Electroencephalogram c. EKG d. Head CT  Won’t show the cause of the seizure in this patient e. Potassium level MTB S2CK  ‐ p. 537 in this patient 5 Tricyclic Antidepressant Toxicity MTB S2CK  ‐ p. 537 Tricyclic Antidepressants Seizures TCA Toxicity Widened QRS Arrhythmia MTB S2CK  ‐ p. 538 Constipation TCA Toxicity Urinary retention Complex Dry mouth Tricyclic Antidepressants • The best initial treatment of TCA overdose is with sodium bicarbonate – Bicarbonate will protect the heart against arrhythmia – Bicarbonate does not increase urinary y excretion of TCAs as it does for aspirin MTB S2CK  ‐ p. 538 Caustics • Caustic ingestion of acids and alkalis (e.g., drain cleaner) causes –Mechanical damage to oropharynx –Esophageal perforation Stomach perforation–Stomach perforation • Don’t give alkali to reverse acids MTB S2CK  ‐ p. 538 Caustics • Flush out caustics • Use water in high volumes • Endoscopy is performed to assess degree of damage MTB S2CK  ‐ p. 538 Steroids don’t prevent injury from caustics Carbon Monoxide Poisoning • Carbon monoxide (CO) poisoning is the MCC of death in fires MTB S2CK  ‐ p. 538 Thermal injury is always the wrong answer 6 Carbon Monoxide Poisoning • CO binds oxygen to Hb so tightly that carboxyhemoglobin will not release oxygen to tissues • Carboxyhemoglobin acts functionally like anemia MTB S2CK  ‐ p. 538 Source: cdc.gov Carbon Monoxide Poisoning Functional Anemia Carbon Myocardial infarction MTB S2CK  ‐ p. 538 Monoxide Dyspnea Lightheadedness Confusion Seizures Carbon Monoxide Poisoning • No functional difference between absence of blood and carboxyhemoglobin; 60% carboxyhemoglobin = loss of 60% of blood The left ventricle can’t MTB S2CK  ‐ p. 538 The left ventricle can t distinguish between anemia, carboxyhemoglobin, and stenosis of coronary arteries. Which of the following blood gas results would you find in carbon monoxide poisoning? a. pH 7.55 pCO2 50 HCO3 24 b. pH 7.25 pCO2 62 HCO3 38 c. pH 7.46 pCO2 22 HCO3 16  Distracter Respiratory acidosis with metabolic alkalosis Respiratory alkalosis with metabolic acidosis d. pH 7.35 pCO2 26 HCO3 18 MTB S2CK  ‐ p. 538  Carbon Monoxide Poisoning Carbon monoxide poisoning gives normal pO2 because oxygen doesn’t detach MTB S2CK  ‐ p. 538 from hemoglobin Carbon Monoxide Poisoning Diagnostic tests • Routine oximetry will be falsely normal • Most accurate test is a level of carboxyhemoglobin Treatment • Remove patient from exposure • Give 100% oxygen MTB S2CK  ‐ p. 539 7 Carbon Monoxide Poisoning Treatment • Severe disease is treated with hyperbaric oxygen • “Severe” symptoms are defined as: – CNS symptoms – Cardiac symptoms – Metabolic acidosis MTB S2CK  ‐ p. 539 Wikimedia Methemoglobinemia • Methemoglobin is oxidized Hb  Ferric • Ferric = Fe3+ • Ferrous = Fe2+ • Oxidized hemoglobin is brown and ill twill not carry oxygen • “Chocolate-brown blood” MTB S2CK  ‐ p. 539 Methemoglobinemia • Methemoglobinemia from idiosyncratic reaction of hemoglobin to drugs such as: – Benzocaine and anesthetics – Nitrites and nitroglycerin – Dapsonep MTB S2CK  ‐ p. 539 Ferrous Hemoglobin Methemoglobinemia “Ferric Hemoglobin” Benzocaine Nitrites Dapsone Methemoglobinemia/Presentation • The effects of methemoglobinemia are similar to carboxyhemoglobin • Oxygen isn’t delivered to tissues Functional AnemiaMetabolic Acidosis MTB S2CK  ‐ p. 539 Methemoglobinemia Dyspnea Cyanosis Lightheadness Confusion Seizures Headache Methemoglobinemia/Presentation Carbon monoxide: blood abnormally red MTB S2CK  ‐ p. 539 Methemoglobinemia: blood abnormally brown Methemoglobinemia/Diagnostic Tests/ Treatment • Both methemoglobinemia and carboxyhemoglobin give normal pO2 on blood gas • Most accurate test is methemoglobin level • Best initial therapy is 100% oxygen • Most effective therapy is methylene blue, which  half-life of methemoglobin MTB S2CK  ‐ p. 539‐540 Cyanosis + normal pO2 = methemoglobinemia 8 Organophosphate (Insecticide) Poisoning and Nerve Gas • Organophosphates and nerve gas identical in their effects • Nerve gas faster and more severe • Massive increase in acetylcholine by i hibiti t b liinhibiting metabolism MTB S2CK  ‐ p. 540 Organophosphate (Insecticide) Poisoning and Nerve Gas Respiratory arrest Organophosphate Polyuria Bronchospasm Bronchorrhea MTB S2CK  ‐ p. 540 g p p Poisoning y LacrimationSalivation Organophosphate (Insecticide) Poisoning and  Nerve Gas Acetylcholine constricts bronchi and increases bronchial secretions MTB S2CK  ‐ p. 540 56-year-old military commander attacked with nerve gas. Presents with salivation, lacrimation, urination, defecation, and SOB. Pupils are constricted. What is the first step in management? a. Atropine p b. Decontaminate (wash) the patient c. Remove his clothing d. Pralidoxime e. No therapy is effective MTB S2CK  ‐ p. 540  Stabilize first Stabilize first Takes too long Never the right answer Organophosphate (Insecticide) Poisoning and  Nerve Gas Nerve gas and organophosphates are MTB S2CK  ‐ p. 540 g p p absorbed through the skin Digoxin Toxicity/Etiology • Hypokalemia predisposes to digoxin toxicity because potassium and digoxin compete for same site on the Na+/K+- ATPase • Less potassium is bound, moreLess potassium is bound, more digoxin is bound MTB S2CK  ‐ p. 540 K+ Increased Digoxin Binding 9 Digoxin Toxicity/Presentation Yellow Halo Vision Digoxin Arrhythmias Confusion MTB S2CK  ‐ p. 540‐541 g Toxicity y Nausea Vomiting Abdominal Pain Hyperkalemia Digoxin Toxicity/Presentation Hypokalemia Digoxin toxicity Digoxin toxicity Hyperkalemia MTB S2CK  ‐ p. 541 Digoxin toxicity Hyperkalemia Digoxin Toxicity/Diagnostic Tests • Most accurate test: digoxin level • Best initial tests: potassium level and EKG • EKG: downsloping of ST segment in all leads – Atrial tachycardia with variable AV block is the most common digoxin toxic arrhythmia MTB S2CK  ‐ p. 541 Digoxin can produce any arrhythmia Digoxin Toxicity/Diagnostic Tests Digoxin Toxicity/Treatment • Control potassium and give digoxin- specific antibodies • Digoxin-binding antibodies rapidly remove digoxin from circulation MTB S2CK  ‐ p. 541 Strongest indication for digoxin-binding antibodies: CNS and cardiac involvement. Lead Poisoning Abdominal pain lead colic Lead Memory loss Renal Tubule Toxicity (ATN) MTB S2CK  ‐ p. 541 Toxicity y confusion Peripheral Neuropathy “wrist drop” Sideroblastic Anemia 10 Lead Poisoning • “Best initial test”:  level of free erythrocyte protoporphyrin • “Most accurate test”: lead level • “Most accurate test” for sideroblastic anemia: Prussian blue stain MTB S2CK  ‐ p. 541 Lead Poisoning/Treatment • Chelating agents remove lead from body –Succimer: only oral –Ethylenediaminetetraacetic acid (EDTA) and dimercaprol (BAL) are(EDTA) and dimercaprol (BAL) are parenteral MTB S2CK  ‐ p. 541 Mercury Poisoning Oral ingested Neurological problems Nervous, jittery, twitchy, and sometimes MTB S2CK  ‐ p. 541 Lung toxicity & interstitial fibrosis Inhaled hallucinatory Mercury Poisoning • There’s no therapy to reverse pulmonary toxicity • Chelating agents such as dimercaprol and succimer are effective in removing mercury from body and decreasing neurological t i ittoxicity Toxic Alcohols/Methanol and Ethylene Glycol Ethylene glycol Treated w/1 Intoxication Methanol MTB S2CK  ‐ p. 542 Treated w/ 1. Fomepizole 2. Dialysis 1. Intoxication 2. Metabolic Acidosis 3. Increased Anion Gap 4. Osmolar Gap Differences between Methanol and  Ethylene Glycol Methanol Ethylene glycol Source Toxic  Wood alcohol, cleaning  solutions, paint thinner Formic acid/formaldehyde Antifreeze Oxalic acid/oxalate metabolite Presentation Initial diagnostic  abnormality Ocular toxicity  Retinal inflammation Renal toxicity Hypocalcemia,  envelope‐shaped  oxalate crystals in  urineMTB S2CK  ‐ p. 542 11 Toxic Alcohols/Methanol and Ethylene Glycol Osmolar Gap Osmolar gap = measured serum osmolality - calculated osmolality Serum osmolality = 2(Na+) + BUN/2.8 + Glucose/18 MTB S2CK  ‐ p. 542 Ex: Measurement 350 - Calculated 300 = gap of 50 osmoles Ordinary alcohol (ethanol) also  osmolar gap Toxic Alcohols/Methanol and Ethylene Glycol Treatment • Best initial therapy: fomepizole, which inhibits alcohol dehydrogenase and prevents production of toxic metabolite • Only dialysis removes methanol and ethylene glycol MTB S2CK  ‐ p. 542 Snake Bites • Most common injury from snake bites is local wound • Death from snake bites: – Hemolytic toxin: hemolysis, DIC, and damage to endothelial lining of tissuesdamage to endothelial lining of tissues – Neurotoxin: can result in respiratory paralysis, ptosis, dysphagia, and diplopia MTB S2CK  ‐ p. 542‐543 Snake Bites/Treatment Ineffective or dangerous  treatment Beneficial therapy Tourniquets blocking  arterial flow Ice   Pressure Immobilization decreases  Incision and suction,  especially by mouth movement of venom  Antivenin  MTB S2CK  ‐ p. 543 Spider Bites/Presentation • All spider bites present with a sudden, sharp pain that patient may describe as: 1.“I stepped on a nail” 2. “A piece of glass was in my shoe.” MTB S2CK  ‐ p. 543 Differences between Types of Spider Bites Black widow Brown recluse Presentation Lab test Abdominal  pain,  muscle pain Hypocalcemia Local skin  necrosis NoneLab test  abnormalities Treatment   Hypocalcemia Calcium,  antivenin None  Debridement,  steroids,  dapsone MTB S2CK  ‐ p. 543 12 Dog, Cat, and Human Bites • Management of dog, cat, and human bites is essentially identical • They’re managed with: – Amoxicillin/clavulanate – Tetanus vaccination booster if > 5 years since MTB S2CK  ‐ p. 543 last injection • Dog and Cats: Pasteurella multocida • Humans: Eikenella corrodens Human bites are more damaging than dog and cat bites Dog, Cat, and Human Bites Rabies vaccine only if: • Animal has altered mental status/bizarre behavior • Attack was unprovoked, by a MTB S2CK  ‐ p. 544 Attack was unprovoked, by a stray dog that cannot be observed or diagnosed Rabies and Bats If a bat was noted to be in the room and the patient was asleep – VACCINATE! MTB S2CK  ‐ p. 544 asleep VACCINATE! Head Trauma Head Trauma • Any head trauma resulting in altered mental status or loss of consciousness (LOC) is managed first with a head CT • Head CT without contrast is best initial test to detect blood MTB S2CK  ‐ p. 544 – Contrast detects mass lesions such as cancer and abscess, not blood Head Trauma • Concussion: – No focal neurological abnormalities – Normal CT scan LOC = CT – Normal CT scan • Contusion: – Occasionally (rarely) has focal findings – Ecchymoses found on CT (blood mixed in with brain parenchyma) MTB S2CK  ‐ p. 544 13 Contusion MTB S2CK  ‐ p. 544 Head trauma • Subdural and epidural hematomas: usually associated with more severe trauma than a concussion • Impossible to distinguish without head CT, epidural hematoma more frequently with k ll f tskull fracture MTB S2CK  ‐ p. 544 Epidural Hematoma MTB S2CK  ‐ p. 545 Subdural Hematoma Source: Brendan T. Doherty Lucid Interval • Lucid interval is a second loss of consciousness occurring several minutes to several hours after initial loss of consciousness – Patient wakes up after initial LOC, but loses consciousness a second time due to MTB S2CK  ‐ p. 545 accumulation of blood • Time between first and second episodes of LOC is lucid interval Both epidural and subdural hematomas are associated with a lucid interval. Treatment • Concussion: no specific therapy –Wait at least 24 hours before returning to sports • Contusion: vast majority need no specific treatment MTB S2CK  ‐ p. 545 –Rarely need surgical debridement Those with concussion safe to go home. Hospitalization isn’t necessary. Observe at home for altered mental status. 14 Treatment Subdural and epidural hematoma: • Treatment is based on size and signs of compression of brain • Small ones are left alone L h t d ith MTB S2CK  ‐ p. 545 • Large hematomas are managed with: –1. Intubation and hyperventilation –2. Mannitol –3. Drainage Definition of a Large Intracranial hemorrhage • Compression of ventricles or sulci • Herniation with abnormal breathing and unilateral dilation of pupil • Worsening mental status or focal findings MTB S2CK  ‐ p. 546 findings Summary of Severe Head Trauma Concussion Contusion Subdural Epidural No focal   findings No lucid Rarely focal             No lucid +/‐ focal  findings +/‐ lucid +/‐ focal  findings      +/‐ lucidNo lucid  Interval No lucid   Interval +/ lucid  Interval +/ lucid  interval  MTB S2CK  ‐ p. 546 Summary of Severe Head Trauma Concussion Contusion Subdural Epidural Normal CT Ecchymoses Venous,  crescent                                Arterial,  biconvex or  lens‐shaped  hematoma             MTB S2CK  ‐ p. 546 No specific  treatment;  observe at  home No specific  treatment;  observe in  hospital Drain large   ones Drain large  ones 25-year-old man sustains head trauma in MVA. A large epidural hematoma is found. Immediately after intubation and mannitol, surgical evacuation is successfully performed. Which of the following will benefit the patient? a. Repeated doses of mannitol b. Continued hyperventilation c. Proton pump inhibitor (PPI) d. Nimodipine e. Dexamethasone MTB S2CK  ‐ p. 546  Doesn’t reduce mortality Doesn’t always work For SAH only Doesn’t change outcomes Head Trauma Steroids don’t benefit intracranial bleeding. They decrease edema around mass lesions. MTB S2CK  ‐ p. 546 15 Burns & Hypothermia Burns • Best initial therapy for those caught in a fire is 100% oxygen to treat smoke inhalation and CO poisoning • Airway burn is 2nd MCC of death from burns only if there’s been airway MTB S2CK  ‐ p. 547 injury Burns Burns inside mouth Burn Victim Burns inside Stridor MTB S2CK  ‐ p. 547 Indications for Intubation nasopharynx WheezingHoarseness Burns • If airway burn is not present, the 2nd MCC of death is volume loss • Fluid replacement is based on percentage of body surface area (BSA) burned MTB S2CK  ‐ p. 547 burned Volume of Fluid Replacement • Replace with Ringer lactate • Give one-half in first 8 hours, a quarter in second 8 hours, and a quarter in the third 8 hours • Give 4 mL for each percentage of BSA burned (including 2nd and 3rd degree burns) MTB S2CK  ‐ p. 547 burned (including 2nd and 3rd degree burns) for each kilogram of body weight – Head: 9% BSA – Arms: 9% BSA each – Legs: 18% BSA each – Chest or back: 18% BSA each Volume of Fluid Replacement • Patchy burns that aren’t continuous make the percentage of BSA burned hard to assess. Use the width of patient’s hand to make an estimate • Each hand width is 1% of BSA • The short answer is: give the largest amount MTB S2CK  ‐ p. 547 • The short answer is: give the largest amount of Ringer lactate or normal saline listed as a choice; it’s probably the right answer Fluid replacement: (4 mL) × (% BSA burned) × weight (kg) 16 What is the MCC of death several days to weeks after a burn? a. Infection b. Renal failure c. Cardiomyopathy d Lung injury  Rhabdomyolysis causes renal failure Not affected so quickly Most common immediate cause of deathd. Lung injury e. Malnutrition MTB S2CK  ‐ p. 547 Fluid loss doesn’t mean malnutrition Heat Disorders Heat cramps/  exhaustion Heatstroke  Risk  Body temp Exertion; high  outside temp Normal Exertion; high  outside temp Elevated MTB S2CK  ‐ p. 548 CPK and K+ level Treatment  Normal Oral fluids and  electrolytes Elevated  IV fluids;  evaporation Heat Disorders Neuroleptic  malignant syndrome Malignant  hyperthermia Risk  Body temp Antipsychotic  medications Elevated Anesthetics  administered  systemically Elevated MTB S2CK  ‐ p. 548 Body temp CPK and K+ level Treatment  Elevated Elevated Dantrolene or  dopamine agonists:  bromocriptine, cabergoline Elevated Elevated Dantrolene Hypothermia • Look for intoxicated person with hypothermia • MCC of death: cardiac arrhythmia • Best initial step: EKG MTB S2CK  ‐ p. 548 Hypothermia MTB S2CK  ‐ p. 548 Drowning • Manage with airway and administer positive pressure ventilation – Steroids and antibiotics are not beneficial – Salt water drowning: acts like CHF with wet, heavy lungs MTB S2CK  ‐ p. 549 • Wrong answers for drowning include: – Steroids – Antibiotics 17 Drowning • Fresh water drowning: causes hemolysis from absorption of hypotonic fluid into vasculature MTB S2CK  ‐ p. 549 RBC Fresh H20RBC RBC Hemolysis Cardiac Rhythm Disorders Initial Management of Cardiac Arrest • First step : – Make sure patient is truly unresponsive – Call for help: call 911/activate Emergency Medical Services (EMS) • Truly unresponsive MTB S2CK  ‐ p. 549 Truly unresponsive • Chest compressions • Rescue breaths Initial Management of Cardiac Arrest After patient has been shown to be unresponsive, and EMS activated, the next step is: 1. Open airway: head tilt, chin lift, jaw thrust 2. Check pulse and start chest compressions if MTB S2CK  ‐ p. 549 p p pulseless 3. Give rescue breaths if not breathing CPR doesn’t restart the heart; CPR keeps patient alive until cardioversion can be performed. Initial Management of Cardiac Arrest • When is a “precordial thump” the answer? –Very recent onset of arrest ( 18 Pulselessness Asystole • Besides CPR, therapy for asystole is with epinephrine • Vasopressin is alternative to epinephrine MTB S2CK  ‐ p. 550 epinephrine • They both constrict blood vessels in tissues (e.g., skin) • Shunts blood into critical central areas (e.g., heart and brain) Pulselessness Ventricular Fibrillation • Best initial therapy for VF is an immediate, unsynchronized cardioversion followed by CPR • Unsynchronized = defibrillation MTB S2CK  ‐ p. 550 Unsynchronized defibrillation • All electrical cardioversions synchronized except VF and pulseless VT Pulselessness Only VF and VT without a l t h i d MTB S2CK  ‐ p. 550 pulse get unsynchronized cardioversion. Ventricular fibrillation MTB S2CK  ‐ p. 550 Pulselessness • After defibrillation, then is epinephrine or vasopressin followed by another electrical shock • Amiodarone or lidocaine • Magnesium MTB S2CK  ‐ p. 550‐551 • Magnesium • Bretylium is always a wrong answer Pulselessness Ventricular Tachycardia (VT) • Wide complex tachycardia with regular rate • Management entirely based on hemodynamic status – Pulseless VT: manage exactly same way as MTB S2CK  ‐ p. 551 VF – Hemodynamically stable VT: Amiodarone, then lidocaine, then procainamide. If all medical therapy fails, then cardiovert patient 19 Pulselessness Ventricular Tachycardia • Hemodynamically unstable VT: Perform electrical cardioversion several times followed by medications (e.g., amiodarone or lidocaine) MTB S2CK  ‐ p. 551 amiodarone or lidocaine) VT is managed with shock, drugs, and CPR at all times in between the shocks. Ventricular Tachycardia MTB S2CK  ‐ p. 551 Pulselessness Hemodynamic instability is defined as: • Chest pain • Dyspnea/CHF • Hypotension • Confusion MTB S2CK  ‐ p. 551 • These qualities of instability are the same for all rhythm disturbances • Direct intracardiac medication administration is always a wrong answer Pulselessness Pulseless Electrical Activity (PEA) • PEA = electrically normal, but no motor contraction • PEA = no cardiac output MTB S2CK  ‐ p. 551 Pulselessness We synchronize delivery of electricity in cardioversion of VT to prevent worsening of arrhythmia into ventricular fibrillation or asystole MTB S2CK  ‐ p. 551‐552 • PEA: look for patient with a normal EKG and no pulse fibrillation or asystole. Pulselessness/Treatment • PEA treated by correcting underlying cause Tension Pneumothorax Causes of PEA HYPOvolemia HYPO l i Tamponade MTB S2CK  ‐ p. 552 HYPOglycemia HYPOxia HYPOthermia Metabolic acidosis HYPERkalemia HYPOkalemia Massive PE 20 Atrial Arrhythmias • Atrial rhythm disturbances rarely associated with hemodynamic compromise • Look for : – Palpitations, dizziness, or lightheadedness MTB S2CK  ‐ p. 552 p , , g – Exercise intolerance or dyspnea – Embolic stroke Atrial Arrhythmias • Irregularly irregular rhythm suggests A- fib as “the most likely diagnosis” even before EKG is done • A fib: most common arrhythmia in the MTB S2CK  ‐ p. 552 • A-fib: most common arrhythmia in the United States Atrial Arrhythmias Atrial Fibrillation and Atrial Flutter • Two disorders with nearly identical management • Major points of difference are: Fl tt i l h th MTB S2CK  ‐ p. 552 –Flutter is a regular rhythm vs. fibrillation is irregular –Flutter changes to sinus rhythm or deteriorates into fibrillation Atrial Fibrillation MTB S2CK  ‐ p. 553 Source: Abhay Vakil, MD. Atrial Flutter MTB S2CK  ‐ p. 553 Atrial Arrhythmias/Treatment • Hemodynamically unstable atrial arrhythmias = synchronized cardioversion • Synchronization prevents electricity from being delivered during refractory MTB S2CK  ‐ p. 553 from being delivered during refractory period (ST-T wave) • Synchronization prevents change into VT or VF 21 Atrial Arrhythmias/Treatment Chronic Atrial Fibrillation • A-fib > 2 days • > 7 days risk of clot formation • Routine cardioversion is not i di t d MTB S2CK  ‐ p. 553‐554 indicated • Chronic is usually secondary atrial or valvular anatomic change Atrial Arrhythmias/Treatment Chronic Atrial Fibrillation • Shocking doesn’t correct a dilated left atrium causing A-fib • Over 90% will revert to fibrillation • Rate control and warfarin is standard of care f A fib MTB S2CK  ‐ p. 553‐554 for A-fib Chronic A-fib should be anticoagulated before cardioversion. Unstable, acute disease doesn’t need anticoagulation. Atrial Arrhythmias/Treatment • Best initial therapy for fibrillation and flutter is to control the rate 1. Goal HR < 100/minute 2. INR between 2-3 – 1 Slow rate MTB S2CK  ‐ p. 554 1. Slow rate – 2. Anticoagulate Rate control drugs do not convert patient into sinus rhythm. Atrial Arrhythmias/Treatment • Calcium-channel blockers used to control HR with atrial arrhythmias are diltiazem and verapamil –Reliably block AV node –Other calcium-channel blockers control MTB S2CK  ‐ p. 554 BP No matter how much you might think it better to shock every patient into sinus, it just doesn’t work in long run. Atrial Arrhythmias/Treatment Warfarin • Without anticoagulation 6% a year stroke risk • INR 2-3, rate: 2-3% stroke risk Dabigatran and Rivaroxaban MTB S2CK  ‐ p. 554 Dabigatran and Rivaroxaban • Alternatives to warfarin • For non-valvular A-Fib • No INR monitoring Atrial Arrhythmias/Treatment • A-fib is caused by anatomic cardiac defects dilating atrium • That’s why vast majority revert • Acute disease normalizes spontaneously; don’t force it MTB S2CK  ‐ p. 554 • Chronic disease reverts into arrhythmia; don’t force it either 22 Atrial Arrhythmias/Treatment Atrial rhythm problems can cause acute PE from loss of atrial “kick” in those MTB S2CK  ‐ p. 554 loss of atrial kick in those with cardiomyopathy. Atrial Arrhythmias/Treatment Lone Atrial Fibrillation • Patients with low risk of stroke can use ASA • 2-3% per year vs. 1% per year bleeding S i i ll d CHADS MTB S2CK  ‐ p. 554 • Scoring is called CHADS score • CHADS ≥ 2 = warfarin, dabigatran, rivaroxiban Atrial Arrhythmias/Treatment “Major” bleeding from warfarin is defined as: I t i l h h MTB S2CK  ‐ p. 554 • Intracranial hemorrhage • Requires transfusion Atrial Arrhythmias/Treatment • Definition/Criteria for Low Risk of Stroke from A-fib – No cardiomyopathy/CHF/atherosclerosis – No HTN – Age ≤ 75 – No diabetes – No stroke in past MTB S2CK  ‐ p. 555 No stroke in past • The answer for management of lone atrial fibrillation is: – Rate control – Aspirin – No warfarin or dabigatran Atrial Arrhythmias/Treatment Supraventricular Tachycardia SVT Vagal Maneuvers Carotid Massage Valsalva Dive Reflex MTB S2CK  ‐ p. 555 Beta Blockers CCBs Digoxin Adenosine Ice immersion Atrial Arrhythmias/Treatment MTB S2CK  ‐ p. 555 Source: Abhay Vakil, MD. 23 Atrial Arrhythmias/Treatment Wolff-Parkinson-White Syndrome (WPW) • WPW is an anatomic abnormality in cardiac conduction pathway • Answer “most likely diagnosis” question by looking for: – SVT alternating with ventricular tachycardia MTB S2CK  ‐ p. 556 SVT alternating with ventricular tachycardia – SVT gets worse after diltiazem or digoxin – Observing delta wave on EKG Vagal maneuvers slow  and convert SVT. They don’t convert atrial fibrillation. Atrial Arrhythmias/Treatment MTB S2CK  ‐ p. 556 • Most accurate test for WPW is cardiac electrophysiology (EP) studies Atrial Arrhythmias/Treatment • Acute therapy: Procainamide or amiodarone • Chronic therapy: Radiofrequency catheter ablation is curative for WPW – EP studies tell you where the anatomic MTB S2CK  ‐ p. 556 defect is • Digoxin and calcium-channel blockers are dangerous in WPW Atrial Arrhythmias Multifocal Atrial Tachycardia • Multifocal atrial tachycardia (MAT) is associated with chronic lung disease such as COPD • Treat underlying lung disease MTB S2CK  ‐ p. 556 • Treat underlying lung disease • Treat MAT as you would A-fib, but avoid beta blockers because of lung disease Atrial Arrhythmias MTB S2CK  ‐ p. 557 Woman comes to office for routine evaluation. She’s found to have a pulse of 40 and an otherwise completely normal history and physical examination. What is the most appropriate next step in the management of this patient? a. Atropine You don’t know the rhythm yet b. Pacemaker c. EKG d. Electrophysiology studies e. Epinephrine f. Isoproterenol g. Nothing; reassurance MTB S2CK  ‐ p. 557  y y Too invasive Too invasive Can result in ischemia Old and no longer used; always wrong Without EKG cannot say 24 Bradycardia and AV block • Isoproterenol is never the right answer to anything MTB S2CK  ‐ p. 557 Bradycardia and AV block Sinus Bradycardia Sinus Bradycardia MTB S2CK  ‐ p. 558 SymptomaticAsymptomatic No Treatment Atropine 1st Pacemaker – Long Term Bradycardia and AV block First-Degree AV block • Use same management as sinus bradycardia Atropine and pacemaker are used MTB S2CK  ‐ p. 558 p p for sinus bradycardia only if symptomatic. Bradycardia and AV block Second-Degree AV block • Mobitz I or Wenckebach block: progressively lengthening PR interval results in a “dropped” beat • Mobitz I is most often a sign of normal aging of conduction system. If there are no symptoms, it’s MTB S2CK  ‐ p. 558 y y p , managed the same way as sinus bradycardia • Don’t treat if asymptomatic Bradycardia and AV block Second-Degree AV block • Mobitz II block: far more pathologic than Mobitz I • Mobitz II just drops a beat without progressive lengthening of PR interval. Mobitz II progresses or deteriorates into third-degree AV block. Treat it like third-degree AV block. Everyone with Mobitz II MTB S2CK  ‐ p. 558 block gets a pacemaker even if they are asymptomatic Bradycardia and AV block MTB S2CK  ‐ p. 558 25 58-year-old woman is admitted to hospital with an acute MI. On the second hospital day she develops sustained VT even though she is on aspirin, heparin, lisinopril, and metoprolol. What is the most appropriate next step in management? a. Increase the dose of metoprolol b. Add diltiazem c. Angiography for angioplasty or bypass d. Implantable defibrillator e. EP studies MTB S2CK  ‐ p. 559  Won’t treat ischemia Will not affect rhythm Underlying cause can be fixed Not ectopy, but rather from ischemia Which of the following tests would you do for this patient to determine a risk of recurrence? a. EP studies b. Echocardiography c. MUGA scan (nuclear ventriculography) d. Ventilation/perfusion scan  For unexplained syncope For perfusion For PE studyp e. Tilt-table testing MTB S2CK  ‐ p. 559 For PE study For syncope 73-year-old man has his third syncopal episode in last 6 months. An EKG done in the field shows VT. His stress test is normal. What is the most appropriate next step in the management of this patient? a. Metoprolol Not enough to prevent death b. Diltiazem c. Angiography d. Implantable defibrillator e. EP studies MTB S2CK  ‐ p. 559‐560  g p EKG shows cause so need for EP Have no affect in VT Normal stress therefore no need for angio 46-year-old man has intermittent episodes of palpitations, lightheadedness, and near-syncope. His EKG is normal. The echo shows an EF of 42%. Holter monitor shows several runs of wide complex tachycardia lasting 5-10 seconds. Which of the following is most likely to benefit this patient? a. Pacemaker placement b. Digoxin c. Warfarin d. EP studies e. Swan-Ganz catheter MTB S2CK  ‐ p. 560  Don’t know underlying cause yet Swan if for diagnosing SHOCK Does nothing for vent arrhythmias Low risk for clot 1 Endocrinology Dr. Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Pituitary Disorders Panhypopituitarism Diabetes Insipidusp Acromegaly Hyperprolactinemia Panhypopituitarism/Etiology • Compression or damage of the pituitary gland • Tumors, cancer, adenomas, cysts, meningiomas, craniopharyngiomas, or lymphoma • Trauma and radiation are damaging MTB S2CK  ‐ p. 107 The Pituitary Gland MTB S2CK  ‐ p. 107 Panhypopituitarism/Etiology Conditions such as: • Hemochromatosis • Sarcoidosis • Histiocytosis X • Infection with fungi TB or parasitesInfection with fungi, TB, or parasites • Autoimmune and lymphocytic infiltration damages gland MTB S2CK  ‐ p. 107 Panhypopituitarism/Presentation  Prolactin deficiency • Men – No symptoms • Women: – Prolactin = “In favor of” or “pro” lactation p – If deficient, the patient cannot lactate normally after childbirth MTB S2CK  ‐ p. 107 2 Panhypopituitarism/Presentation  Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deficiency • Both genders will have decreased libido and decreased axillary, pubic, and body hair • Men – Unable to produce testosterone or spermUnable to produce testosterone or sperm – Erectile dysfunction and decreased muscle mass • Women – Unable to ovulate or menstruate normally and become amenorrheic MTB S2CK  ‐ p. 107 Panhypopituitarism/Presentation  Growth hormone (GH) deficiency • Adults –Few symptoms • Children –Dwarfism • Catecholamines, glucagon, and cortisol act as stress hormones MTB S2CK  ‐ p. 108 Panhypopituitarism/Presentation  Kallman Syndrome • Decreased FSH and LH • Decreased GnRH • Anosmia MTB S2CK  ‐ p. 108 Panhypopituitarism/Diagnostic Tests Hyponatremia from: • Hypothyroidism • Glucocorticoid underproduction • Potassium levels remain normal – Aldosterone is unaffected and aldosteroneAldosterone is unaffected and aldosterone excretes potassium MTB S2CK  ‐ p. 108 Panhypopituitarism/Diagnostic Tests • MRI detects compressing mass lesions on pituitary MTB S2CK  ‐ p. 108 Source: James G. Smirniotopoulos, MD  Panhypopituitarism/Diagnostic Tests Growth Hormone (GH) • IGF level • Arginine Stimulation: increases GH • GHRH stimulation: increases GH ACTH and Cortisol levels Hi h l l l l d h it it i• High or normal levels excludes panhypopituitarism Sex Hormones • LH, FSH level • Testosterone level Thyroid • TSH MTB S2CK  ‐ p. 108 3 Panhypopituitarism/Diagnostic Tests Older, Less Useful Tests Metyrapone • Inhibits 11-beta hydroxylase and decreases cortisol • Normal: ACTH and 11deoxycortisol levels rise I li ti l tiInsulin stimulation • Normal: decreased glucose levels raise GH • Failure of GH to rise in response to insulin indicates pituitary insufficiency MTB S2CK  ‐ p. 109 Panhypopituitarism/Treatment Replace deficient hormones with... • Thyroxine • Cortisone • Testosterone and estrogen • Recombinant human growth hormone • Antidiuretic hormone (ADH) and oxytocin (Posterior Pituitary) Note: No deficiency disease described for oxytocin • Oxytocin helps uterine contraction during delivery, but delivery still occurs even if it’s absent • ADH deficiency also known as central diabetes insipidus MTB S2CK  ‐ p. 109 Diabetes Insipidus/Etiology Decrease in amount of ADH from pituitary (central DI) or its effect on kidney (nephrogenic DI) Central Diabetes Insipidus (CDI) • Damage to brain: – Stroke– Stroke – Tumor – Trauma – Hypoxia – Infiltration (sarcoidosis, hemochromatosis) – Infection MTB S2CK  ‐ p. 109 Diabetes Insipidus/Etiology Nephrogenic DI (NDI): • Chronic pyelonephritis • Amyloidosis • Myeloma • Sickle cell diseaseSickle cell disease • Lithium • Hypercalcemia or hypokalemia inhibits ADH effect MTB S2CK  ‐ p. 109 Diabetes Insipidus/Presentation   • Excessive thirst • Extremely high-volume urine • Volume depletion Severe Hypernatremia  Neurological symptoms C f i di i t ti l th d t ll• Confusion, disorientation, lethargy, and eventually seizures and coma • Only when volume losses are unmatched by fluid intake MTB S2CK  ‐ p. 109 Diabetes Insipidus/Diagnostic Tests   • Urine osmolality: Low • Urine sodium: Low • Serum osmolality: High • Urine volume: Enormous MTB S2CK  ‐ p. 110 4 Diabetes Insipidus/Diagnostic Tests   Difference between central and nephrogenic DI is: Response to vasopressin Central DI: • Urine volume decrease & urine osmolality increase Nephrogenic DI: • No effect of vasopressin use on urine volume or osmolality MTB S2CK  ‐ p. 110 Diabetes Insipidus/Treatment Central DI: • Long-term vasopressin (desmopressin) Nephrogenic DI: 1. Correct the cause (hypokalemia or hypercalcemia) 2. Hydrochlorothiazide, NSAIDs, amiloride MTB S2CK  ‐ p. 110 Diabetes Insipidus/Evaluation High-volume urine, plus excessive thirst Volume depletion, plus hypernatremia Urine: Volume: HIGH Osmolality: Decreased Serum: Osmolality: Elevated MTB S2CK  ‐ p. 109 Osmolality: Decreased Sodium: DecreasedSodium: Elevated Proceed with vasopressin (desmopressin) stimulation test Diabetes Insipidus/Evaluation Urine: Volume decrease + osmolality increase Urine: No effect Vasopressin (Desmopressin) stimulation test Effect MTB S2CK  ‐ p. 110 Central diabetes insipidus Nephrogenic diabetes insipidusDiagnosis Treatment Vasopressin Treat underlying cause, hydrochlorothiazide, amiloride, NSAIDs Acromegaly  Soft tissue overgrowth throughout the body MTB S2CK  ‐ p. 110 Copyright Richard Usatine, M.D. Used with permission. Acromegaly/Etiology  Pituitary adenoma • Part of Multiple Endocrine Neoplasias (MEN) • Combined with parathyroid and pancreatic disorders (e g gastrinomapancreatic disorders (e.g., gastrinoma or insulinoma) • Rarely caused by ectopic GH or GHRH production MTB S2CK  ‐ p. 110 5 Acromegaly/Presentation • Increased hat, ring, and shoe size • Carpal tunnel syndrome • Obstructive sleep apnea from soft tissues enlarging • Body odor from sweat • Colonic polyps • Arthralgias from joints growing out of alignment • Hypertension for unclear reasons in 50% gland hypertrophy • Teeth widening from jaw growth • Deep voice and macroglossia (big tongue) • Cardiomegaly, CHF, and erectile dysfunction from increased prolactin cosecreted with pituitary adenoma MTB S2CK  ‐ p. 110‐111 Acromegaly/Diagnostic Tests  • Hyperglycemia • Glucose intolerance • Hyperlipidemia Best initial test... • Insulin-like growth factor (IGF) M t t t tMost accurate test... • Glucose suppression test • Normal: Glucose should suppress growth hormone MRI? • Only after the laboratory identification of acromegaly MTB S2CK  ‐ p. 111 Acromegaly/Treatment 1. Surgery – Transphenoidal resection of pituitary – Cures 70% 2. Medications – Cabergoline: Dopamine agonist inhibits GH release – Octreotide or lanreotide: Somatostatin inhibits GH release – Pegvisomant: GH receptor antagonist 3. Radiotherapy – Only when not responsive to surgery or medications MTB S2CK  ‐ p. 111 Hyperprolactinemia/Etiology  Many causes not associated with pituitary adenoma Prolactin increases via: • Cosecretion with GH in acromegaly g y • Hypothyroidism with pathologically high TRH levels MTB S2CK  ‐ p. 111 Hyperprolactinemia/Etiology  • Pregnancy • Chest wall stimulation • Cutting pituitary stalk • Antipsychotic medications, tricyclic antidepressants, and SSRIsp , • Methyldopa • Metoclopromide • Opioids MTB S2CK  ‐ p. 111 Hyperprolactinemia/Presentation Women • Galactorrhea • Amenorrhea • Infertility Men • Erectile dysfunction • Decreased libido • Galactorrhea (very rare in men) MTB S2CK  ‐ p. 111 6 Hyperprolactinemia/Diagnostic Tests  After the prolactin level is found to be high, perform: • Thyroid function tests • Pregnancy test • BUN/creatinine (kidney disease elevates prolactin) • Liver function tests (cirrhosis elevates prolactin) MRI is done after... • High prolactin level is confirmed AND • Secondary causes like medications are excluded AND • Patient is not pregnant MTB S2CK  ‐ p. 112 Hyperprolactinemia/Treatment 1. Dopamine agonists – Cabergoline is better tolerated than bromocriptine 2 Transphenoidal surgery when NOT2. Transphenoidal surgery when NOT responding to medications 3. Radiation is rarely needed MTB S2CK  ‐ p. 112 Thyroid Disorders Hypothyroidism HyperthyroidismHyperthyroidism Thyroid Nodules What to look for... Hypothyroidism Hyperthyroidism Tachycardia, palpitations,  arrhythmia (A‐fib) Diarrhea (hyperdefecation) Weight loss Bradycardia Constipation Weight gain MTB S2CK  ‐ p. 113 Anxiety, nervousness,  restlessness Hyperreflexia Heat intolerance Fever  Fatigue, lethargy, coma Decreased reflexes Cold intolerance Hypothermia (hair loss,  edema) Hypothyroidism  Etiology • Most from failure of thyroid gland from burnt-out Hashimoto thyroiditis – Acute phase is rarely perceived • Dietary deficiency of iodine • Amiodarone• Amiodarone What to look for... • Hypothyroidism: Everything is SLOW! • Except menstrual flow, which is increased MTB S2CK  ‐ p. 112 Hypothyroidism Diagnostic tests • Best initial test for all thyroid disorders is... – TSH • TSH levels are markedly elevated if gland has failed • If the TSH level is suppressed, measure... – T4T4 Treatment • Replace thyroxine (synthroid) MTB S2CK  ‐ p. 113 7 Hyperthyroidism/Findings Diagnosis Unique feature Graves disease Subacute thyroiditis Painless “silent” thyroiditis Eye proptosis (20‐40%) Skin findings (5%) Tender thyroid Nontender normal P/E MTB S2CK  ‐ p. 113 Painless  silent thyroiditis Exogenous thyroid  hormone use Pituitary adenoma Nontender, normal P/E  Involuted gland isn’t  palpable High TSH level Myxedema Multinodular Goiter Thyroid Bruit Hyperthyroidism/Diagnostic Tests T4 (thyroxine) level • Elevated in all forms of hyperthyroidism TSH level • Pituitary release of TSH is inhibited in all forms EXCEPT... MTB S2CK  ‐ p. 113‐114 • Pituitary adenomas, will have high TSH level Graves disease (unique features): • Eye and skin abnormalities • Elevated radioactive iodine uptake • TSH receptor antibodies Hyperthyroidism/Treatment Graves Ophthalmopathy • Best initial therapy... – Steroids • For those unresponsive to steroids...to steroids... – Radiation • What if unresponsive to other therapy... – Decompressive surgery MTB S2CK  ‐ p. 114 Source: Jonathan Trobe, MD 8 Hyperthyroidism/Treatment Diagnosis Treatment Graves disease Subacute thyroiditis Painless “silent” thyroiditis Radioactive iodine Aspirin None MTB S2CK  ‐ p. 114 y Exogenous thyroid  hormone use Pituitary adenoma Stop use Surgery Acute Hyperthyroidism/“Thyroid Storm” Treatment: Propranolol • Blocks target organ effect • Inhibits peripheral conversion of T4→T3 Thiourea drugs • Methimazole and propylthiouracil • Block hormone production MTB S2CK  ‐ p. 114 Acute Hyperthyroidism/“Thyroid Storm” Treatment: Iodinated contrast material • Blocks peripheral conversion of T4 to T3 • Blocks release of existing hormone Steroids (hydrocortisone) • Role in treating hyperthyroidism? Radioactive iodine • Ablates gland for permanent cure MTB S2CK  ‐ p. 114 Thyroid Nodules • 5% women • 1% men • 95% benign –Adenoma, colloid nodule, cyst • Thyroid nodules rarely hyperfunctioning MTB S2CK  ‐ p. 114 46-year-old woman with a small mass on palpation of thyroid. No tenderness and otherwise asymptomatic. What is the most appropriate next step? a. Fine-needle aspiration b Radionuclide iodine uptake scan Done if TFTs are normal Determines etiologyb. Radionuclide iodine uptake scan c. T4 and TSH levels d. Thyroid ultrasound e. Surgical removal (excisional biopsy) MTB S2CK  ‐ p. 115  Determines etiology of hyperfunctionality Guides biopsy Follicular adenoma when you can’t be sure Thyroid Nodules/Diagnostic Tests  • Biopsy with a fine-needle aspirate if there’s normal thyroid function (T4/TSH) • Ultrasound or radionuclide scanning not required (tests cannot exclude cancer) MTB S2CK  ‐ p. 115 9 46-year-old woman with thyroid nodule and normal thyroid function testing has a biopsy showing “indeterminate for follicular adenoma.” What is the most appropriate next step? a Neck CT Doesn’t make a diagnosis, determines extent a. Neck CT b. Surgical removal (excisional biopsy) c. Ultrasound d. Calcitonin levels MTB S2CK  ‐ p. 115  g , Can’t excluded cancer, still need biopsy Suggests extent of medullary carcinoma only Calcium Disorders Hypercalcemia Hyperparathyroidism Hypocalcemia Hypercalcemia/Etiology  • Vitamin D intoxication • Sarcoidosis and other granulomatous diseases • Thiazide diuretics • Hyperthyroidism yp y • Metastases to bone and multiple myeloma MTB S2CK  ‐ p. 116 Hypercalcemia/Etiology  Most common cause is... • Primary hyperparathyroidism (PTH) – Most cases are asymptomatic – Severe, acute symptomatic hypercalcemia  a high prevalence of cancer a high prevalence of cancer MTB S2CK  ‐ p. 116 Hypercalcemia/Presentation   Acute, symptomatic hypercalcemia • Confusion, stupor, lethargy • Constipation • Bone lesions: Osteoporosis • Renal: Nephrolithiasis DI renal insufficiency• Renal: Nephrolithiasis, DI, renal insufficiency • Cardiovascular: Short QT syndrome MTB S2CK  ‐ p. 116 Hypercalcemia/Treatment   Acute hypercalcemia, treat with... • Saline hydration at high volume • Bisphosphonates: pamidronate, zoledronic acid • Calcitonin Prednisone: • ONLY for sarcoidosis and granulomatous disease MTB S2CK  ‐ p. 116 10 75-year-old man with history of malignancy admitted with lethargy, confusion, and abdominal pain. Found to have a markedly elevated calcium level. After 3L normal saline and pamidronate, his calcium level is still markedly elevated the following day. What is the most appropriate next step in management? a Calcitonina. Calcitonin b. Zolendronic acid c. Plicamycin d. Gallium e. Dialysis f. Cinacalcet MTB S2CK  ‐ p. 116‐117  Less efficacy than pamidronate. Always wrong Doesn’t add to pamidronate Less efficacy than pamidronate. Always wrong Not needed. Renal failure has low Ca++ Inhibits PTH Hyperparathyroidism  Primary hyperparathyroidism: • Solitary adenoma (80%–85%) • Hyperplasia of all 4 glands (15%–20%) • Parathyroid malignancy (1%) MTB S2CK  ‐ p. 117 Hyperparathyroidism  Elevation in calcium levels often asymptomatic When symptomatic: • Osteoporosis • Nephrolithiasis and renal insufficiency • Muscle weaknessMuscle weakness • Anorexia, nausea, vomiting, and abdominal pain • Peptic ulcer disease (calcium stimulates gastrin) MTB S2CK  ‐ p. 117 Hyperparathyroidism  Besides high calcium and PTH levels, you also find: • Low phosphate level • Short QT on EKG • Sometimes an elevated BUN and creatinineSometimes an elevated BUN and creatinine • Alkaline phosphatase elevated from effect of PTH on bone MTB S2CK  ‐ p. 117 Hyperparathyroidism/Management  • Bone X-ray is NOT a good test for bone effects of  PTH • DEXA densitometry is better • Preoperative imaging of neck with sonography or nuclear scanning may be helpful in determining the surgical approach MTB S2CK  ‐ p. 117 Hyperparathyroidism/Treatment • Surgical removal of involved parathyroid glands MTB S2CK  ‐ p. 117‐ 118 11 Hypocalcemia Low calcium = twitchy, hyperexcitable High calcium = lethargic, slow MTB S2CK  ‐ p. 118 Hypocalcemia/Presentation  Neural hyperexcitability: • Chvostek sign (facial nerve hyperexcitability) • Carpopedal spasm • Perioral numbness • Mental irritability• Mental irritability • Seizures • Trousseau sign (tetany) MTB S2CK  ‐ p. 118 Souce: nih.gov Hypocalcemia/Diagnosis & Treatment EKG: • Prolonged QT • May cause arrhythmia – Ventricular tachycardia TreatmentTreatment • Replace calcium and vitamin D MTB S2CK  ‐ p. 118 Adrenal Disorders Hypercortisolism Hyperparathyroidism Hypocalcemia Pituitary‐Adrenal Axis Source: nih.gov Hypercortisolism Cushing disease • Pituitary overproduction of ACTH Cushing’s syndrome • Due to ectopic production of ACTH C i id ( t i ll ll i f– Carcinoid (most common is small cell carcinoma of the lung) – Overproduction autonomously in adrenal gland • Prednisone (glucocorticoid use) causes same manifestations of hypercortisolism MTB S2CK  ‐ p. 119 12 Hypercortisolism/Etiology Cause of Hypercortisolism Frequency Pituitary ACTH  (Cushing disease) Adrenals E i ACTH 70% 15% 10% MTB S2CK  ‐ p. 119 Ectopic ACTH  (carcinoid) Unknown source of ACTH 10% 5% Hypercortisolism/Presentation  Fat redistribution “Moon face,” truncal obesity, “buffalo hump,” thin extremities, increased abdominal fat Skin HTN From increased sodium reabsorption in kidney and increased vascular reactivity Menstrual disorders Striae, easy bruising, decreased wound healing, thinning of skin Osteoporosis Erectile dysfunction Polyuria From hyperglycemia and increased free water clearance MTB S2CK  ‐ p. 119 Hypercortisolism/Diagnostic Tests Always confirm the source of hypercortisolism with biochemical tests before you perform imaging studies • 10% of population has an abnormality of pituitary10% of population has an abnormality of pituitary on MRI • If you start with a scan, you may remove the pituitary when the source is in the adrenals MTB S2CK  ‐ p. 120 Hypercortisolism/Diagnostic Evaluation CC: “I feel weak and tired, and I notice hair growth on my face and strange marks on my stomach” 24-hour urine cortisol Low-dose (1mg) dexamethasone suppression test Late-night salivary cortisol Decreased = High? MTB S2CK  ‐ p. 119‐120 Increased Disease Excluded Increased Serum ACTH ACTH-dependent Cushing’s syndrome ACTH-independent Cushing’s syndrome Low? Hypercortisolism/Diagnostic Evaluation ACTH-independent Cushing’s syndrome ACTH-dependent Cushing’s syndrome CT Adrenals High-dose dexamethasone i t t Adrenal Mass? Pituitary vs. Ectopic ACTH production? MTB S2CK  ‐ p. 120 suppression test Pituitary MRI Petrosal sinus sampling for ACTH Supression of cortisol? Pituitary adenoma (Cushing disease) Increased ACTH & cortisol? Pituitary Mass? Ectopic ACTH- secreting tumor Chest CT No mass seen? Confirmatory Laboratory Findings in Adrenal Disorders Adrenal Pituitary  Ectopic ACTH level Petrosal sinus Low Not done High High ACTH High  Low ACTH MTB S2CK  ‐ p. 121 ACTH High‐dose dexamethasone No suppression g Suppresses Cortisol No suppression 13 Hypercortisolism/Other Findings Cortisol - anti-insulin stress hormone • Hyperglycemia • Hyperlipidemia There’s some aldosterone-like effect of cortisol H k l i• Hypokalemia • Metabolic alkalosis • Leukocytosis from demargination of WBCs MTB S2CK  ‐ p. 120 Hypercortisolism/Treatment  • Surgically remove source of hypercortisolism – Transsphenoidal surgery for pituitary sources – Laparoscopic removal for adrenal sources MTB S2CK  ‐ p. 121 Evaluation of Adrenal “Incidentaloma” How far should you go in the evaluation of an unexpected, asymptomatic adrenal lesion found on CT? 1. Metanephrines of blood or urine to exclude pheochromocytoma 2 Renin and aldosterone levels to exclude2. Renin and aldosterone levels to exclude hyperaldosteronism 3. 1 mg overnight dexamethasone suppression test MTB S2CK  ‐ p. 121 Hypoadrenalism (Addison’s)/Etiology Addison’s disease • Chronic hypoadrenalism • Etiology – Autoimmune destruction (80%) Adrenal crisis • Acute adrenal insufficiency • Etiology – Hemorrhage, surgery, hypotension, trauma( ) – Infection (TB) – Adrenoleukodystrophy – Metastatic cancer to adrenal gland yp , – Suddenly stopping chronic high-dose prednisone MTB S2CK  ‐ p. 121 Hypoadrenalism/Presentation  • Weakness, fatigue • Altered mental status • Nausea, vomiting, anorexia, hypotension • Hyperpigmentation from chronic adrenal • Acute adrenal crisis can also present with profound hypotension, fever, confusion, and coma chronic adrenal insufficiency MTB S2CK  ‐ p. 121‐122 Copyright Richard Usatine, MD Used with permission.  Hypoadrenalism/Diagnostic Tests  • Hypoglycemia • Hyperkalemia • Metabolic acidosis • Hyponatremia • Pituitary failure: –ACTH is low • Adrenal failure: • High BUN • Eosinophilia is common in hypoadrenalism –ACTH is high MTB S2CK  ‐ p. 122 14 Hypoadrenalism Signs & Symptoms • Weakness • Hypotension • Weight Loss • Hyperpigmentation Cosyntropin Stimulation Test Plasma cortisol before & after 250 ug cosyntropin IM or IV MTB S2CK  ‐ p. 121‐122 Cortisol fails to rise • Low ACTH • Aldosterone an increase • High ACTH • Aldosterone Low too Primary adrenal insufficiency Secondary adrenal insufficiency Adrenal atrophy from pituitary insufficiency Hypoadrenalism/Treatment • Treatment is more important than testing in acute adrenal crisis • Replace steroids with hydrocortisonep y • Fludrocortisone – For postural instability – A steroid hormone particularly high in mineralocorticoid or aldosterone-like effect MTB S2CK  ‐ p. 122 Patient brought to ED after sustaining severe abdominal trauma in MVA. On second hospital day, he becomes markedly hypotensive without evidence of bleeding. There’s fever, high eosinophil count, hyperkalemia, hyponatremia, and hypoglycemia. What is the next step? Norepinephrine will constrict a. CT scan of the adrenals b. Draw cortisol level and administer hydrocortisone c. Cosyntropin stimulation testing d. ACTH level e. Dexamethasone suppression testing MTB S2CK  ‐ p. 122‐123  Treating severe hypotension more important than finding etiology Norepinephrine will constrict vessels more effectively Primary Hyperaldosteronism “The autonomous overproduction of aldosterone despite a high pressure with a low renin activity” Solitary adenoma: 80% Bilateral hyperplasia:15-20% Malignant: 1% MTB S2CK  ‐ p. 123 Primary Hyperaldosteronism • All forms of secondary HTN are more likely in those whose onset is... – < 30 or > 60 years – Uncontrolled by 2 antihypertensive medications • Has a characteristic finding on the history, physical,Has a characteristic finding on the history, physical, or labs • Primary hyperaldosteronism = High BP + Low K+ MTB S2CK  ‐ p. 123 Primary Hyperaldosteronism/Diagnostic Tests  Best initial test... • Plasma aldosterone to plasma renin ratio • A low plasma renin with high aldosterone = Primary hyperaldosteronism Most accurate test... • Adrenal venous blood sampling  high aldosterone! CT Scan? • Only after laboratory testing reveals... – Low potassium, low plasma renin, and high aldosterone despite a high-salt diet MTB S2CK  ‐ p. 123 15 Primary Hyperaldosteronism/Treatment  Unilateral adenoma • Resected by laparoscopy Bilateral hyperplasia • Eplerenone or spironolactone Spironolactone causes... • Gynecomastia • Decreased libido • Anti-androgenic MTB S2CK  ‐ p. 124 Pheochromocytoma • Nonmalignant lesion of adrenal medulla • Autonomous overproduction of catecholamines despite high BP Pheochromocytoma is the answer when there’s: • Episodic HTN• Episodic HTN • Headache • Sweating • Palpitations and tremor MTB S2CK  ‐ p. 124 Pheochromocytoma/Diagnostic Tests  Best initial test... • Plasma catecholamines Confirmed with... • 24-hour urine metanephrines and catecholamines – More accurate than VMA level MTB S2CK  ‐ p. 124 Pheochromocytoma/Diagnostic Tests  Imaging of adrenal glands (CT or MRI) • Done only after biochemical testing MIBG scanning • Nuclear isotope scan D t t l ti f h h t th t• Detects location of pheochromocytoma that originates outside adrenal gland MTB S2CK  ‐ p. 124 Pheochromocytoma/Diagnostic Tests  MIBG scan showing unilateral pheochromocytoma Source: Laura N Modzelewski Pheochromocytoma/Treatment 1. Phenoxybenzamine: (IV alpha blocker) 2. Propranolol 3. Calcium-channel blocker (possible) 4. Laparoscopic removal MTB S2CK  ‐ p. 124 16 Diabetes Mellitus Presentation DiagnosisDiagnosis Treatment Diabetic Ketoacidosis Health Maintenance Complications Diabetes Mellitus (DM) Persistently  fasting blood glucose levels > 125  on at least 2 separate occasions  • Type 1 DM − Onset in childhood Insulin dependent from • Type 2 DM − Onset in adulthood Directly related to− Insulin dependent from early age − Not related to obesity − Insulin deficiency − Directly related to obesity − Insulin resistance MTB S2CK  ‐ p. 124‐125 Diabetes Mellitus/Presentation   • Polyuria, polyphagia, and polydipsia • Type 1 DM: thinner than Type 2 diabetics • Type 2 DM: more resistant to diabeticType 2 DM: more resistant to diabetic ketoacidosis (DKA) • Both types:  wound healing MTB S2CK  ‐ p. 125 Diabetes Mellitus/Diagnostic Tests   • 2 FBG measurements > 125 mg/dL • One glucose level about 200 mg/dL with symptoms • Abnormal oral glucose tolerance testing • Hemoglobin A1c > 6.5% MTB S2CK  ‐ p. 125 Diabetes Mellitus/Treatment Best initial treatment... Diet, exercise, and weight loss • Weight loss controls as much as 25% of cases of type 2 DM without medications,yp , • Exercising muscle doesn’t need insulin MTB S2CK  ‐ p. 125 Diabetes Mellitus/Treatment Oral Hypoglycemic Medications • Best initial drug: metformin • Metformin blocks gluconeogenesis • Sulfonylureas  insulin release from pancreas  weight gain Dipeptidyl Peptidase Inhibitors • Increase insulin • Decrease glucagon • Sitagliptin, Saxagliptin, Linagliptin MTB S2CK  ‐ p. 125 17 Diabetes Mellitus/Treatment Thiazoladinediones (glitazones) Rosiglitazone, Pioglitazone • Relatively contraindicated in CHF • Increase fluid overload Nateglinide and repaglinide • Stimulates insulin release • Similar to sulfonylureas • No additional therapeutic benefit to sulfonylureas MTB S2CK  ‐ p. 125‐126 Diabetes Mellitus/Treatment Incretins (exenatide, liraglutide) • Raise insulin • Decrease glucagon levels • Decrease gastric motility • Helps in weight lossHelps in weight loss MTB S2CK  ‐ p. 126 Diabetes Mellitus/Treatment Alpha-glucosidase inhibitors (acarbose, miglitol) • Block glucose absorption in bowel • Cause flatus, diarrhea, and abdominal pain Pramlintide A l f t i ll d li th t’ t d• Analog of protein called amylin that’s secreted normally with insulin • Amylin – decreases gastric emptying – decreases glucagon levels – decreases appetite MTB S2CK  ‐ p. 125‐126 Diabetes Mellitus/Treatment Insulin • Added if patient isn’t controlled with oral hypoglycemic agents • Insulin glargine gives steady state of insulin for entire day • Dosing isn’t testedDosing isn t tested • Glargine provides much more steady blood levels than NPH insulin • Combined with short-acting insulin (e.g., lispro, aspart, or glulisine) MTB S2CK  ‐ p. 126 Diabetes Mellitus MTB S2CK  ‐ p. 126 Diabetes Mellitus/Treatment • Pharmacokinetics of insulin formulations Drug Type Onset (hr) Peak (hr) Duration (hr) Aspart Glulisine Lispro Rapid-acting 0.2–0.5 0.5–2 3–4 Regular Short-acting 0.5–1 2–3 6–8 MTB S2CK  ‐ p. 126 NPH Intermediate 1.5 4–10 16–24 Lente Intermediate 1.5–3 7–15 16–24 Ultralente Long-acting 3–4 9–15 22–28 Glargine Long-acting No peak 24–36 18 Diabetic Ketoacidosis (DKA)  • More common with type 1 diabetes • Can definitely present in type 2 diabetes Presents with... • Hyperventilation • Altered mental status M t b li id i ith i d i• Metabolic acidosis with increased anion gap • Hyperkalemia in blood, but decreased total body potassium because of urinary spillage • Increased anion gap on blood testing • Serum is positive for ketones MTB S2CK  ‐ p. 126 Diabetic Ketoacidosis/Treatment  Treat with... 1. Large-volume saline and insulin replacement 2. Replace potassium when potassium level approaches normal 3. Correct the underlying cause y g – Noncompliance with medications – Infection – Any serious illness MTB S2CK  ‐ p. 127 57-year-old man admitted to ICU with altered mental status, hyperventilation, and markedly elevated glucose level. Which of the following is the most accurate measure of the severity of his condition? a. Glucose level b. Serum bicarbonate c. Urine ketones d. Blood ketones e. pH level on blood gas MTB S2CK  ‐ p. 127 Can be elevated without DKA Mean very little Not all blood ketones are detected Need to know what’s responsible for pH level If very low, there’s risk of death Diabetes Mellitus/Health Maintenance  All patients with DM should receive... • Pneumococcal vaccine • Yearly eye exam to check for proliferative retinopathy, which needs laser therapy • Statins to get LDL < 100 mg/dLg g • ACEi or ARBs to get BP < 130/80 mmHg • ACEi or ARB if urine tests positive for microalbuminuria • Foot exam for neuropathy and ulcers MTB S2CK  ‐ p. 127 Complications of Diabetes  Gastroparesis • Immobility of bowels • Bloating, constipation • Early satiety, vomiting • Abdominal discomfortAbdominal discomfort • Treat with metoclopramide or erythromycin MTB S2CK  ‐ p. 128 Complications of Diabetes  Non-proliferative retinopathy • Tighter control of glucose • Aspirin doesn’t help retinopathy Proliferative retinopathyProliferative retinopathy • Neovascularization and vitreous hemorrhages • Treated with laser photocoagulation MTB S2CK  ‐ p. 128 19 Complications of Diabetes Neuropathy • Decreased sensation in feet • Main cause of skin ulcers • Leads to osteomyelitis • Treatment pain withTreatment pain with – Pregabalin – Gabapentin – Tricyclic antidepressants MTB S2CK  ‐ p. 128 1 Ethics Dr. Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Autonomy Advance Directives Minors i hBrain Death Ethics “Every human being of adult years and sound mind has the right to determine what shall be done with his own body; and a surgeon who performs an operation without his patient’s consent commits an assault, for which he is liable in damages…except in cases of emergency where the patient is unconscious and h it i t t b f twhere it is necessary to operate before consent can be obtained. Justice Benjamin Cardozo, Schloendorff v. Society of New York Hospital, 211 NY 125, 105 NE 92 (1914) MTB S2CK  ‐ p. 561 Ethics This states the premise underlying half the ethics questions on S2 CK of USMLE: 1. Autonomy 2. Adult 3 C it t d t d3. Capacity to understand MTB S2CK  ‐ p. 561 Autonomy • Patients have sole right to determine what treatment they shall and shall not accept • Autonomy beats “Beneficence” • Beneficence: trying to do good for others • Trying to help not as important as following y g p p g wishes MTB S2CK  ‐ p. 561 Patients have the right to refuse treatments that are good for them if they don’t want them. A man has an ugly house you offer to paint free in his favorite color. Everyone in neighborhood agrees the house is ugly & what you offer is clearly superior. He understands everything you are offering, including the clear benefit to him. The man still refuses. What do you do? a. Honor the man’s wishes: no paint job Cost and benefit and the common good aren’t as important as the autonomy individuals have to just do h t th t ith th ia. Honor the man s wishes: no paint job b. Paint his house against his will c. Ask the neighborhood council to consent to the paint job d. Get a psychiatric evaluation on the man e. Get a court order to allow the paint job f. Ask his family for consent to the paint job g. Wait until he is out of town, then paint his house MTB S2CK  ‐ p. 561‐562 what they want with their own property.  2 Man comes to ED after MVA that causes a ruptured spleen. He’s fully conscious. He understands that he’ll die without splenectomy, and that he’ll live if he has the splenectomy. He refuses the repair and blood transfusion. Entire family including brother who is healthcare proxy and document completed only a few weeks ago clearly state, “Everything possible should be done, including surgery.” What do you do? ya. Honor his current wishes, no surgery b. Wait until he loses consciousness, then perform the surgery c. Psychiatric consult d. Ethics committee e. Emergency court order f. Follow what is written in the documented health-care proxy g. See if there is consensus from the family MTB S2CK  ‐ p. 562 You must follow the last known wishes of the patient, even if they are verbal, and even if they contradict the written proxy. You cannot wait until his consciousness is lost, then go against his wishes.  Advance Directives • Tell caregivers parameters of care the patient wanted • “Agent” = person designated by patient to carry out patient’s wishes • Term “Agent” sometimes used interchangeably with healthcare proxy • Healthcare proxy is written document outlining parameters of care • Major problem with proxy is details of care often unclear MTB S2CK  ‐ p. 562 Advance Directives • Not helpful to just say, “No heroic measures” • To be useful, document must specifically state, “No intubation, no CPR, no chemotherapy, no dialysis” • Can also specifically state wishes about fluid and nutrition • If proxy says, “No NG tube, no artificial feeding,” then it’s useful • Proxy takes effect only when patient has lost capacity to make decisions MTB S2CK  ‐ p. 561‐562 Advance Directives Order of Decision Making 1. Patient with capacity supersedes all else 2 H lth t ( )2. Healthcare proxy: an agent (person) to carry out wishes MTB S2CK  ‐ p. 563 Advance Directives Order of Decision Making 3. Living will – Document outlining patient’s wishes – Stating, “I never want dialysis” is more valid than a family member or friend saying, “From what I know b t hi h ld ’t t di l i ” “H t ldabout him, he wouldn’t want dialysis,” or “He told me he never wants dialysis.” – Documentation! • Written living will with concrete statements “I never want blood transfusion or chemotherapy” is valid MTB S2CK  ‐ p. 563 Advance Directives Order of Decision Making 4. Persons clearly familiar with the patient’s wishes – Problem with documentation – Difficult for friends to document they knew theDifficult for friends to document they knew the patient’s wishes – If case clearly states friend knows and can prove that she knew the patient’s wishes, then this is the plan of care that’s followed MTB S2CK  ‐ p. 563 3 Advance Directives Order of Decision Making 5. Family • General order of decision making 1. Spouse 2 Adult children2. Adult children 3. Parents 4. Siblings • Unlike life, USMLE S2 CK must be clear • If family is split, then answer is: – Ethics committee or court order MTB S2CK  ‐ p. 563 Advance Directives Ethics Committee The answer when: 1. Patient has lost capacity to make decisions 2 Advance directive is missing or unclear2. Advance directive is missing or unclear Critically important for “medical futility” • E.g. when the patient or proxy asking for tests and treatments that may have no benefit MTB S2CK  ‐ p. 563 Advance Directives “Court order” is right answer when: • There’s no advance directive and 1. Patient has no capacity 2. Family in disagreement • Like a house being left equally to four children g q y who cannot agree what to do with it • Caregivers want to withdraw care and ethics committee cannot reach a conclusion MTB S2CK  ‐ p. 563 Advance Directives Psychiatric Evaluation of Patient The answer when... • It is not clear if patient has capacity Question clearly states patient has capacity?Question clearly states patient has capacity? • Not necessary! Clearly delirious or psychotic? • Not necessary! MTB S2CK  ‐ p. 563 Minor Minors do not have decision-making capacity • Cannot consent to or refuse medical treatments • Only parents or legal guardian can consent and refuse Exceptions are: • Contraception • Prenatal care • Substance abuse treatment • Sexually transmitted diseases (STDs) including HIV/AIDS MTB S2CK  ‐ p. 564 Minor Abortion • States are split on parental notification laws • Some require it, some don’t Y i• Your answer is: “Tell the minor patient to notify her parents.” MTB S2CK  ‐ p. 564 4 Brain Death Brain death = death in our legal system • If brain dead, you don’t need consent to stop therapy such as mechanical ventilation or antibiotics • Court order and ethics committee aren’t correct answers MTB S2CK  ‐ p. 564 USMLE S2 CK will want you to discuss, educate, explain, and confer before everything else. Consent Do Not Resuscitate Orders Physician‐Assisted Suicide EuthanasiaEuthanasia Terminal Sedation and  Law of Double Effect Futile Care Organ and Tissue Donation Consent • Only adults can consent to procedures • Each procedure needs individual consent • Consent implied in emergency • Person doing procedure must obtain consent • Adverse effects of procedure must be explained to make consent validmake consent valid • Consequences of refusing procedure must be explained to make consent valid • Pregnant women can refuse procedures and treatments for their unborn children • Telephone consent is valid MTB S2CK  ‐ p. 564 Consent Patient signs consent for ovarian biopsy on left side. At surgery you find cancer of right side. What do you do? Wake patient up & obtain consent to remove ovary on right side. MTB S2CK  ‐ p. 564 Patient needs colonoscopy. Gastroenterologist asks you to obtain consent for procedure. What do you do? The gastroenterologist who will perform the procedure needs to obtain consent. • Do you know all complications of the procedure and Consent • Do you know all complications of the procedure and alternatives? • If you don’t explain the possibility of perforation because you are unfamiliar with it, the consent isn’t valid • If patient’s colon perforates and you didn’t explain alternate procedures, the consent isn’t valid MTB S2CK  ‐ p. 564 Do Not Resuscitate Orders • DNR orders refer only to withholding CPR • They don’t refer to withholding any other form of therapy MTB S2CK  ‐ p. 565 5 Do Not Resuscitate Orders Patient with capacity consents to DNR before losing consciousness. She needs a surgical procedure, but the surgeon refuses because the patient is DNR. What do you do? • Perform the surgery • DNR doesn’t mean withholding antibiotics, chemotherapy, or surgery • DNR means only that, if the patient dies, you won’t attempt resuscitation MTB S2CK  ‐ p. 565 Physician‐Assisted Suicide Always a wrong answer! • This includes states in which it’s legal • Ethical requirements for physicians supersede legality • Physician-assisted suicide is administered byPhysician assisted suicide is administered by the patient, but this is still unethical for physicians MTB S2CK  ‐ p. 565 Physician ethics come before legal requirements. You cannot do something unethical even if it’s legal at the moment. Euthanasia • Physician-administered treatment intended to end or shorten patient’s life Always wrongy g MTB S2CK  ‐ p. 565 Terminal Sedation and  Law of Double Effect • Is it acceptable to administer pain medication even if there’s the possibility treatment shortens life? • For example, it’s acceptable to give pain medications to a person with COPD who hasmedications to a person with COPD who has metastatic cancer even if the only way to relieve pain is to give enough opiates that breathing may be impaired, causing the patient to die earlier MTB S2CK  ‐ p. 565 Terminal Sedation and  Law of Double Effect • The question is one of intent: • If the meds are given with intent to relieve pain, and as an adverse effect they shorten life, it’s ethical • If the primary intent is to shorten life, it’s unethical MTB S2CK  ‐ p. 565 Futile Care • Physician not obligated to render care that’s futile even if the family or patient wants it • If brain dead & family insists on continued mechanical ventilation youcontinued mechanical ventilation, you are under no obligation to do so • You are under no obligation to perform tests and treatments you consider worthless MTB S2CK  ‐ p. 565 6 Organ and Tissue Donation • Payment for ORGANS is unacceptable • Payment for RENEWABLE tissues (sperm & eggs) is acceptable MTB S2CK  ‐ p. 565 Consent for Organ Donation • Only organ donor network should ask for consent for organs • Ethical conflict of interest for physician to ask for consent for organ donation • Organ donor network has fewer refusals than physician • Organ donor cards give an indication of patient’s wishes, but family can refuse organ donation even if patient has organ donor card MTB S2CK  ‐ p. 566 Physician Responsibilities ConfidentialityConfidentiality Doctor/Patient Relationship Gifts from Industry Abuse Impaired Drivers Execution of Prisoners Torture Confidentiality • Patient’s right to confidentiality can be broken when there’s danger to others • STDs • HIV/AIDS Ai b i bl di (• Airborne communicable diseases (e.g., tuberculosis) • Court order demanding information MTB S2CK  ‐ p. 566 Confidentiality Right to confidentiality cannot be broken for: • Employers • Coworkers • Government agencies • Family • Friends MTB S2CK  ‐ p. 566 Confidentiality is important, but not as important as protecting others from harm. Patient with HIV/AIDS has repeatedly refused to disclose his HIV status to his sexual partner. The partner accompanies the patient to the office visits and is in the waiting room. The patient insists you not tell the partner. What do you do? a. Honor the patient’s wishes b. Obtain a court order c. Consult the ethics committee d. Either the physician or the department of health can notify the partner MTB S2CK  ‐ p. 566  The confidentiality of the patient is not as important as protecting the health of the partner. 7 Confidentiality Woman comes to your office with valid identification from a law enforcement/government agency. She requests a copy of your patient’s medical records. What do you do? Provide health-related protected records to government agencies, including those from law f t l ifenforcement, only if: – Valid warrant or subpoena from courts – Otherwise violates the constitutional protection against illegal search and seizure of property – This violates HIPAA, which protects health information MTB S2CK  ‐ p. 566 Confidentiality HIV-positive healthcare workers do not have to disclose their status to their patients or their employers. MTB S2CK  ‐ p. 566 Doctor/Patient Relationship • Physicians aren’t obligated to accept everyone coming to him or her as a patient • You have the right to end the doctor/patient relationship but must give the patient sufficient time to obtain another caregiver S ll ift f ti t t bl• Small gifts from patients are acceptable as long as they aren’t tied to a specific treatment request • Romantic or sexual contact between patients and their current physicians is never acceptable MTB S2CK  ‐ p. 566‐567 Gifts from Industry Never acceptable! • Even pens, penlights, pads, and cups are unacceptable • Meals in direct association with educational activities aren’t considered gifts MTB S2CK  ‐ p. 567 Elder Abuse • You can report elder abuse against the consent of patient • Abused older adults may be too weak, fragile, or vulnerable to protect themselvesthemselves • Elder abuse is treated ethically like child abuse MTB S2CK  ‐ p. 567 Domestic Violence and Spousal Abuse • Unlike child abuse, domestic abuse cannot be reported against the patient’s wishes • You can report and intervene only with patient’s consentpatient s consent MTB S2CK  ‐ p. 567 8 Impaired Drivers  (Seizure Disorders and Driving) • Least clear area nationally • No uniformity of laws between states • Answer “suggest that the patient find another means of transportation” • Wrong answers would be: a. Confiscating car keys and reporting to law enforcement b. Hospitalizing patient c. Refusing to let the patient get in car MTB S2CK  ‐ p. 567 Execution of Prisoners • Never ethical for a physician to participate in executions at any level • You cannot ethically formulate a lethal injection or even do so much as pronounce a prisoner deadpronounce a prisoner dead • Even if state law makes execution legal, physicians should never participate at any level MTB S2CK  ‐ p. 567 Torture • Physicians are never to participate in torture of prisoners or detainees • Even if the question states that you’re in the military, your ethical obligation as a physician supersedes your obligation to the ilitmilitary • This would include: a. Refusing orders from military superiors to participate in torture b. Keeping the torture “safe” so that it’s not fatal or damaging MTB S2CK  ‐ p. 567‐568 Torture Torture is the ethical equivalent of child abuse. Your participation is never MTB S2CK  ‐ p. 568 p p acceptable; you’re obligated only to report it. 1 Gastroenterology Niket Sonpal, MD Chief Resident Lenox Hill Hospital‐NSLIJ Assistant Clinical Professor ‐ Touro College of Medicine Esophagus   Achalasia Esophageal Cancer Esophageal SpasmEsophageal Spasm Esophagitis Rings and Webs Zenker’s Diverticulum Scleroderma Mallory‐Weiss Tear Boerhaave’s Syndrome Esophageal Disorders/Definitions  Dysphagia • Difficulty swallowing Odynophagia • Pain while swallowing MTB S2CK  ‐ p. 237 Esophageal Disorders/Presentation  • Both can lead to weight loss • Hence, weight loss cannot be used to answer “What is the most likely diagnosis?” With the symptoms • Weight loss• Weight loss • Anemia • Heme-positive stool MTB S2CK  ‐ p. 237 Endoscopy! Achalasia/Diagnosis  Inability of lower esophageal sphincter (LES) to relax due to a loss of nerve plexus within lower esophagus • Etiology unclear • Aperistalsis of esophageal body MTB S2CK  ‐ p. 237 Chagas Disease = recent travel to South America and new onset dysphagia Achalasia/Diagnosis  Look for... • Young patient (< 50) • Progressive worsening dysphagia to both solids and liquids at the same time • No association with alcohol and tobacco use • Complain of... – Regurgitation and halitosis MTB S2CK  ‐ p. 237 2 Achalasia/Diagnostic Tests  Barium esophagram • Will show a “birds beak” MTB S2CK  ‐ p. 238 Source: commons.wikimedia.com Marked Dilation of the Esophagus Source: Niket Sonpal, MD Achalasia/Diagnostic Tests  Most accurate test is… Manometry MTB S2CK  ‐ p. 238 Source: Niket Sonpal, MD Achalasia/Diagnostic Tests  Chest X-ray • May show abnormal widening of esophagus, but is neither very sensitive nor very specific MTB S2CK  ‐ p. 238 Chest X-ray is never the right answer to diagnose achalasia Achalasia/Diagnostic Tests  Upper endoscopy • Shows normal mucosa in achalasia MTB S2CK  ‐ p. 238 Source: Niket Sonpal, MD Achalasia/Treatment • Cannot exactly be “cured” • All treatment is based on simple mechanical dilation of esophagus MTB S2CK  ‐ p. 238 3 Achalasia/Treatment Pneumatic dilation • Effective > 80% to 85% of patients • Repeat sessions are necessaryy MTB S2CK  ‐ p. 238 Source: commons.wikimedia.com Achalasia/Treatment Botulinum toxin injection • Will relax LES, but effects wear off in about 3-6 months, requiring reinjection Site of Botulinum Injection MTB S2CK  ‐ p. 238 Freedictionary.com Injection Achalasia/Treatment • Surgical sectioning or myotomy can help to alleviate symptoms • Known as Heller M tMyotomy MTB S2CK  ‐ p. 238 Niket Sonpal MD Esophageal Cancer/Diagnosis Look for: • Age 50 or older • Dysphagia with solids first then progresses to liquids • Association with prolonged alcohol and p g tobacco use • > 5 years of GERD symptoms MTB S2CK  ‐ p. 239 • Endoscopy is indispensible, since only a biopsy can diagnose cancer – “NO TISSUE, NO ISSUE” Esophageal Cancer/Diagnostic Tests  • Barium cannot diagnose cancerdiagnose cancer MTB S2CK  ‐ p. 239 Source: commons.wikimedia.com Esophageal Cancer/Diagnostic Tests  • CT and MRI scans – Only shows extent of tissue • PET scan – Gives information about other anatomicGives information about other anatomic lesions MTB S2CK  ‐ p. 239 4 Esophageal Cancer/Treatment  • Surgical resection is always the thing to try – No resection (removal) = no cure • Chemotherapy and radiation MTB S2CK  ‐ p. 239 Esophageal Cancer/Treatment  Stent placement • Purely palliative MTB S2CK  ‐ p. 239 Source: Niket Sonpal, MD Esophageal Spasm/Background • Diffuse esophageal spasm (DES) and nut- cracker esophagus are clinically indistinguishable • Both present – Sudden onset of chest pain – Not related to exertion MTB S2CK  ‐ p. 239 Esophageal Spasm/Diagnosis • EKG and stress – Normal • Esophagram – best initial test – Normal • Manometry – most accurate testy – Abnormal contraction in various section of the esophagus MTB S2CK  ‐ p. 239 Esophageal Spasm/Treatment • Treated with: • Nitrates – Relax smooth muscle • Calcium-channel blockers – No Ca+2= no smooth muscle contractionNo Ca no smooth muscle contraction MTB S2CK  ‐ p. 240 Esophageal Spasm/Barium Study MTB S2CK  ‐ p. 240 5 43-year-old man recently diagnosed with AIDS comes to ED with pain on swallowing that’s become progressively worse over the last several weeks. There’s no pain when not swallowing. His CD4 count is 43 mm3. The patient isn’t currently taking any medications. What is the most appropriate next step in management? a Esophagram Doesn’t diagnose candidaa. Esophagram b. Upper endoscopy c. Oral nystatin swish and swallow d. Intravenous amphotericin e. Oral fluconazole MTB S2CK  ‐ p. 240  Doesn t diagnose candida Too invasive Too “big gun” Only for oral candida Infectious Esophagitis/Management  Yes Dysphagia with HIV CD4 < 100 Empirically start fluconazole Yes NoImprovementYes Continue therapy and HAART Perform upper endoscopy with biopsy HSV – small ulcerations. Tx: acyclovir CMV – large ulcerations. Tx: ganciclovir or foscarnet Improvement Infectious Esophagitis Source: Aaron Cho Rings and Webs  Schatzki ring • Schatzki rings and Plummer-Vinson syndrome both cause dysphagia MTB S2CK  ‐ p. 241 Source: commons.wikimedia.com Rings and Webs  Schatzki ring • Associated with intermittent dysphagia MTB S2CK  ‐ p. 241 Source: Azmeena Laila, MD Rings and Webs  Plummer-Vinson syndrome Triad of: 1. Dysphagia due to Esophageal Webs 2. Iron Deficiency Anemia 3. Glossitis M i l th S h t ki i• More proximal than Schatzki rings • Diagnosis – Barium esophagram • Treatment – Iron replacement MTB S2CK  ‐ p. 241 6 Zenker’s Diverticulum  • Outpocketing of posterior pharyngeal constrictor muscles MTB S2CK  ‐ p. 241 Stanford Hospital Media Zenker’s Diverticulum  • Best test for diagnosis is – Esophogram • No medical treatment and surgical intervention is best MTB S2CK  ‐ p. 241 Source: commons.wikimedia.com Scleroderma Presentation • Symptoms of reflux • Scleroderma or progressive systemic sclerosis Diagnosis • Manometry Treatment • PPIs • Screening for Barrett’s esophagus MTB S2CK  ‐ p. 242 • Upper GI bleed secondary to repetitive retching • Self-limited • Dx: endoscopy Mallory‐Weiss Syndrome/Presentation MTB S2CK  ‐ p. 242 Source: commons.wikimedia.com Mallory‐Weiss Syndrome/Treatment  • No specific therapy and will resolve spontaneously • Severe cases with persistent bleeding are managed with injection of epinephrine or electrocautery to stop bleeding MTB S2CK  ‐ p. 242 Boerhaave’s Syndrome • Esophageal rupture due to prolonged retching – A full thickness tear • Physical exam – Hammen’s sign - crepitus – Subcutaneous air = “snap crackle and pop” • EMERGENCY! Source: commons.wikimedia.com 7 Stomach   Epigastric Pain Gastroesophageal Reflux Disease Barrett’s Esophagus Gastritis Peptic Ulcer Disease Non‐ulcer Dyspepsia Gastrinoma Diabetic Gastroparesis 44-year-old woman comes to see you because of epigastric pain for several months. She denies nausea, vomiting, weight loss, or blood in her stool. On physical examination you find no abnormalities. What is the most likely diagnosis? a. Duodenal ulcer disease No anemia or heme (+) stools b. Gastric ulcer disease c. Gastritis d. Pancreatitis e. Non-ulcer dyspepsia f. Pancreatic cancer MTB S2CK  ‐ p. 242‐243  Acute not chronic Heme (+) stools Need EGD to diagnose No painless jaundice Abdominal Pain/Causes of Pain by Location Right Upper Quadrant Cholecystitis Biliary colic Cholangitis Perforated duodenal ulcer Left Upper Quadrant Splenic rupture IBS – Splenic flexure syndromeMid-Epigastrium Pancreatitis Left Lower Quadrant Sigmoid volvulus Sigmoid diverticulitis Ovarian torsion Ectopic pregnancy Right Lower Quadrant Appendicitis Ovarian torsion Ectopic pregnancy Cecal diverticulitis Aortic dissection Peptic ulcer disease Epigastric Pain/Most Likely Diagnosis If this is in the history: The most likely diagnosis is:  Pain worse with food Pain better with food Weight loss Tenderness Gastric ulcer Duodenal ulcer Cancer, gastric ulcer Pancreatitis MTB S2CK  ‐ p. 243 Tenderness Bad taste, cough, hoarse Diabetes, bloating Nothing Pancreatitis Gatroesophageal reflux Gastroparesis Non‐ulcer dyspepsia Epigastric Pain/Diagnostic Tests  Endoscopy • Only way to truly understand the etiology of epigastric pain from ulcer disease • Only way to give a y y g precise diagnosis MTB S2CK  ‐ p. 243 Wikimedia Epigastric Pain/Treatment  Proton pump inhibitors (PPIs) • First line therapy • Empiric • Minimum 4 weeks Liquid antacids • Roughly the same efficacy as H2 blockers Misoprostol • Artificial prostaglandin H2 blockers • Ranitidine, nizatidine, cimetidine, famotidine • Not as effective, but will work in about 70% of patients analogue • Used to treat NSAID- induced gastric damage • When PPIs arrived, misoprostol became wrong answer MTB S2CK  ‐ p. 243 8 Gastroesophageal Reflux Disease (GERD) • Inappropriate relaxation of LES • Results in acid contents of stomach coming up into esophagus Patient complains of... • Heartburn• Heartburn • Metallic taste • Cough MTB S2CK  ‐ p. 244 42-year-old man comes to office with epigastric pain radiating up under his chest, which becomes worse after lying flat for an hour. He also has a “brackish” taste in his mouth. What is the most appropriate next step in the management of this patient? a. Ranitidine b. Liquid antacid c. Lansoprazole d. Endoscopy e. Barium swallow f. 24-hour pH monitoring MTB S2CK  ‐ p. 244  Not as effective Not as effective Not an anatomic disease Not the first step – must fail 1st Too invasive GERD/Diagnostic Tests  • Most often diagnosed using patient history • When not clear, the most accurate test is... – 24-hour pH monitoring Endoscopy when: Dysphagia or odynophagia• Dysphagia or odynophagia • Weight loss • Anemia or heme-positive stools • > 5 years of symptoms to exclude Barrett’s esophagus MTB S2CK  ‐ p. 244‐245 GERD/Treatment • All patients should try lifestyle changes – Lose weight, avoid alcohol, nicotine and certain foods, eat within 3 hours of bedtime – Elevate head 6-8 inches • Mild or Intermittent Symptoms – May be treated with liquid antacids or H2 blockers • Persistent Symptoms or Erosive Esophagitis – PPIs for 4-6 weeks MTB S2CK  ‐ p. 245 GERD/Treatment 5% will not respond to PPIs Patients require surgery to tighten LES: • Nissen fundoplication – Stomach wrapped around LES • Endocinch• Endocinch – Scope used to place a suture around LES • Local heat or radiation of LES – Causes scarring to tighten LES – Last resort MTB S2CK  ‐ p. 245 Barrett’s Esophagus  • Due to long-standing GERD • Change to columnar metaplasia • Typically takes 5 years Diagnosis • Biopsy via endoscopy – Only way to assess presence of Barrett’s esophagus MTB S2CK  ‐ p. 245 9 Barrett’s Esophagus/Treatment Finding Management Barrett’s alone  (metaplasia) Low‐grade dysplasia PPIs and rescope every 2‐ 3 years PPIs and rescope every  6‐12 months MTB S2CK  ‐ p. 246 High‐grade dysplasia Ablation with endoscopy,  photodynamic therapy,  radiofrequency ablation,  or surgical removal Gastritis • Inflammation or erosion of gastric lining • Sometimes called gastropathy – 3 levels: mild, moderate and severe – With or without hemorrhage • Many causes Alcohol– Alcohol – NSAIDs – Helicobacter pylori – Portal HTN – Stress • Burns, trauma, sepsis, multiorgan failure MTB S2CK  ‐ p. 246 Gastritis/Presentation • Often with GI bleeding without pain • Severe, erosive gastritis can present with epigastric pain • Look for NSAIDs or alcoholism in history • No unique physical findingsq p y g – You cannot answer the “most likely diagnosis” question from history and physical alone MTB S2CK  ‐ p. 246 Gastritis/Diagnosis • The most accurate test is... – EGD • H. pylori testing Capsule endoscopy is not appropriate for upper GI bleeding if endoscopy is one of the choices py g – Treated if associated with gastritis MTB S2CK  ‐ p. 246 Source: commons.wikimedia.org Testing for Helicobacter pylori Test What is good  about this test? Endoscopic  biopsy Serology Most accurate of  all tests Inexpensive,  excludes infection  if negative What is bad  about this test? Invasive test  (endoscopy) Lacks specificity,  can’t distinguish    current/previous MTB S2CK  ‐ p. 246‐247 Urea C13 or C14 breath testing H. Pylori     stool antigen if negative Positive only in  active infection,  noninvasive Positive only in  active infection,  noninvasive current/previous  infection Requires expensive  equipment Requires stool  sample Gastritis/Treatment • Treat with PPIs • H2 blockers, sucralfate, and liquid antacids aren’t effective as PPIs MTB S2CK  ‐ p. 247 Sucralfate is an inert substance (aluminum hydroxide complex) that coats the stomach. If sucralfate is presented as a choice, it’s nearly always the wrong answer. 10 Gastritis Stress ulcer prophylaxis is indicated in: • Mechanical ventilation • Burns – Curling’s ulcers • Head trauma – Cushing’s ulcers • CoagulopathyCoagulopathy MTB S2CK  ‐ p. 247 Peptic Ulcer Disease (PUD)     • PUD refers to both duodenal ulcer and gastric ulcer disease • Endoscopy is key to diagnosis and treatment • MCCs – H. pylori and NSAIDs – Note: Alcohol and tobacco don’t cause ulcers. They delay healing of ulcers MTB S2CK  ‐ p. 247‐248 Peptic Ulcer Disease Source: commons.wikimedia.orgSource: commons.wikimedia.org Peptic Ulcer Disease/Presentation     • PUD presents with recurrent episodes of epigastric pain Abdominal Pain (dull, sore, gnawing) MTB S2CK  ‐ p. 248 Pain that is improved with eating Pain that is worsened by eating Duodenal Ulcer Gastric Ulcer Peptic Ulcer Disease/Diagnosis     • Upper endoscopy: “most accurate test” – Allows for intervention and biopsy Ulcer on endoscopy Biopsy positive for H. pylori Bleeding ulcer • Radiologic Testing – Poor sensitivity and no histology testing MTB S2CK  ‐ p. 248 Antibiotic treatment Clip or epinephrine injection Peptic Ulcer Disease/Treatment     • PUD responds to PPIs... – But must treat for H. pylori Duodenal Ulcer Gastric Ulcer • Cancer is present in 4% of those with GU but in none of those with DU. MTB S2CK  ‐ p. 248‐249 H. pylori in more than 80% to 90% of cases H. pylori in 50% to 70% of cases 11 Peptic Ulcer Disease/Treatment     • H. pylori Treatment Biopsy positive for H. Pylori PPI combined with Replace amoxicillin PCN allergy? MTB S2CK  ‐ p. 243 clarithromycin and amoxicillin Replace amoxicillin with metronidazole 30-60 day post therapy testing for eradication Peptic Ulcer Disease/Treatment     56-year-old woman comes to clinic with epigastric pain from endoscopically confirmed duodenal ulcer, which is unresponsive to several weeks of PPI, clarithromycin, and amoxicillin. What is the most appropriate next step? a. Refer for surgery Too invasiveg y b. Switch the PPI to ranitidine c. Abdominal CT scan d. Capsule endoscopy e. Urea breath testing f. Vagotomy g. Add sucralfate MTB S2CK  ‐ p. 249  Always the wrong answer Can’t detect H. pylori PPI is superior to ranitidine CT can’t detect H. pylori Not necessary and too invasive Peptic Ulcer Disease/Treatment     Treatment of Refractory Ulcers • If initial therapy doesn’t resolve the DU then detecting persistent H. pylori and switching the antibiotics to metronidazole and tetracycline is appropriate or adding bismuth • For those with refractory GU, a repeat y , p endoscopy is done to exclude cancer MTB S2CK  ‐ p. 249 Gastric Ulcers vs. Duodenal Ulcers  GU is routinely biopsied GU vs. DU Routinely repeating the endoscopy to confirm healing is standard with GU GU is associated with cancer in MTB S2CK  ‐ p. 250 GU pain is more often worsened by food standard with GU 4% Non‐ulcer Dyspepsia  • Non-ulcer (functional) dyspepsia is epigastric pain that has no identified etiology • MCC of epigastric pain in U.S. MTB S2CK  ‐ p. 250 Non‐ulcer Dyspepsia  • The best initial therapy is with PPIs Empiric PPI therapy PPIs and EGD to r/o NUD < 45-55 years NUD > 45-55 years MTB S2CK  ‐ p. 250 cancer Symptoms persist and H. Pylori is present = treat for H. pylori 12 Gastrinoma (Zollinger‐Ellison Syndrome)  Look for patient with ulcers that are: 1. Large > 1 cm 2. Multiple 3. Past 3rd portion of duodenumduodenum 4. Presents with: • Diarrhea • Abdominal pain • Anemia • Heme-positive stools MTB S2CK  ‐ p. 251 Source: commons.wikimedia.org Gastrinoma/Diagnostic Tests   After endoscopy confirms an ulcer, diagnosis made using one of the following three: 1. High gastrin levels after antisecretory therapy (PPIs/H2) 2. High gastrin levels despite a high gastric acid output 3. Persistent high gastrin levels despite injecting secretin (most accurate) MTB S2CK  ‐ p. 251 Source: Niket Sonpal MD Gastrinoma/Diagnostic Tests   What is the next best step after diagnosing ZE? • Exclude metastatic disease  Somatostatin receptor scintigraphy + Endoscopic ultrasound MTB S2CK  ‐ p. 251 Ultrasound, CT, and MRI of abdomen have poor sensitivity and are never the most accurate test for diagnosing ZE Gastrinoma/Treatment  • Local disease is removed surgically • Metastatic disease requires lifelong PPIs to block acid production MTB S2CK  ‐ p. 251 64-year-old patient with diabetes for 20 years comes to the office with several months of abdominal fullness, intermittent nausea, constipation, and a sense of “bloating.” On physical examination, a “splash” is heard over the stomach. What is the next step? a. Abdominal CT scan b. Colonoscopy c. Erythromycin d. Upper endoscopy e. Nuclear gastric emptying study MTB S2CK  ‐ p. 252  Can only diagnose static conditions Wrong end! Wouldn’t reveal anything Most accurate test for diabetic gastroparesis, but rarely used + + Diabetic Gastroparesis Long standing diabetes Resultant dysmotility Autonomic neuropathy from high glycemic index = MTB S2CK  ‐ p. 252 Resultant dysmotility from an inability to sense stretch in the GI tract Nausea, vomiting, and early satiety Diabetic gastroparesis 13 Diabetic Gastroparesis The patient’s most common complaint is abdominal discomfort with eating “large or small meals” Nausea & vomiting Bloating & constipation Upper and Lower Symptoms Endoscopy - large amount of retained food Succussion splash Anorexia Early satiety Neurologic Symptoms Signs elicited by exam Colon Gastrointestinal Bleeding DiarrheaDiarrhea Irritable Bowel Syndrome Inflammatory Bowel Disease Diverticular Disorders Colon Cancer Screening 69-year-old woman comes to ED with multiple red/black stools. Past medical history significant for aortic stenosis. Pulse 115/ minute. BP 94/62 mmHg. Examination otherwise normal. What is the next step in management? a. Colonoscopy b. Nasogastric tube placement c. Upper endoscopy d. Bolus of normal saline e. CBC f. Bolus of 5% dextrose in water g. Consult gastroenterology h. Check for orthostasis MTB S2CK  ‐ p. 252‐253  D5w doesn’t stay intravascular Patient is unstable, Stablized first, THEN diagnose Gastrointestinal Bleeding Upper GI bl di Most common: Ulcer disease MTB S2CK  ‐ p. 253 bleeding Gastritis VaricesEsophagitis Duodenitis Cancer Gastrointestinal Bleeding Lower GI bl di Most common: Diverticulosis MTB S2CK  ‐ p. 253 bleeding IBD HemorrhoidsPolyps UGIB Cancer Gastrointestinal Bleeding/Physical Findings  Severity of Blood Loss Based on Hemodynamics Orthostasis Pulse > 100/minute Systolic BP < 100 mmHg Physical Finding 15‐20% 30% 30% Percentage of blood loss Remember: orthostasis is defined as... • >10-point rise in pulse when going from supine to sitting or standing up or BP drop of 20 points or more when sitting up MTB S2CK  ‐ p. 253 Systolic BP  14 Variceal Bleeding Variceal bleeding Asterixis Cirrhosis Vomiting blood +/– black stool MTB S2CK  ‐ p. 253‐ 254 bleeding Spider angiomata and caput medusa Palmar erythema Splenomegaly Gastrointestinal Bleeding/Diagnostic Tests  For acute severe bleeding • Replace fluids and check Hct, platelet count, and coagulation tests (PT or INR) For variceal bleeding • Octreotide and urgent endoscopy to control the bleed by banding MTB S2CK  ‐ p. 254 Additional Diagnostic Tests for GI Bleeding Test Indication Endoscopy unrevealing in a massive  acute hemorrhage Specific site of bleeding needs  to be identified prior to surgery or  embolization of vessel; used only in  Nuclear bleeding scan Angiography MTB S2CK  ‐ p. 254 y massive, nonresponsive bleeding Small bowel bleeding when upper and  lower endoscopy don’t show etiology Not useful in GI bleeding Shows ischemia in severe bleeding Capsule endoscopy CT or MRI of abdomen EKG Gastrointestinal Bleeding/Treatment  Stabilization Treatment • Fluid replacement – 1-2 liters an hour • Packed RBCs – Hct < 30 in those who are older or suffer from CAD MTB S2CK  ‐ p. 255 Gastrointestinal Bleeding/Treatment  Stabilization Treatment • Fresh frozen plasma – INR > 1.3 • Platelets – < 50,000 when bleeding MTB S2CK  ‐ p. 255 Gastrointestinal Bleeding/Treatment  Treat Underlying Cause • Endoscopy to determine diagnosis and administer treatment (band varices, cauterize ulcers, inject epinephrine into bleeding gastric vessels) • IV PPI for upper GI bleeding • Surgery to remove site of bleeding if fluids, blood, platelets, and plasma will not control bleed MTB S2CK  ‐ p. 255 15 Gastrointestinal Bleeding/Treatment  Esophageal and Gastric Varices • Octreotide (somatostatin) • Banding • Transjugular intrahepatic portosystemic h ti (TIPS)shunting (TIPS) • Propranolol MTB S2CK  ‐ p. 255 Diarrhea/Types Diarrhea Carcinoid syndrome Lactose intolerance Antibiotic- associated diarrhea Chronic pancreatitis Malabsorption Diarrhea/Antibiotic Associated  • Clindamycin associated with highest incidence of antibiotic-associated diarrhea and Clostridium difficile • Blood and white cells may be present in stool • Presents several days or weeks after start of antibiotics • ANY antibiotic can potentially cause diarrhea MTB S2CK  ‐ p. 255 Diarrhea/Antibiotic Associated  • Best initial test is... – Stool C. diff. toxin • Most accurate test is... – C. diff. PCR • Best initial therapy is... Metronidazole– Metronidazole • If there’s no response to metronidazole, next step in management is to... – Switch to oral vancomycin or fidaxomicin MTB S2CK  ‐ p. 255‐ 256 IV vancomycin is always wrong for antibiotic-associated diarrhea since it will not pass bowel wall. 75-year-old man is admitted to hospital with pneumonia. Several days after start of antibiotics, he has diarrhea. Stool C. diff toxin is positive, and he’s started on metronidazole, which leads to resolution of diarrhea over a few days. Two weeks later diarrhea recurs and C. diff toxin is positive again. What is the next step? a. Retreat with metronidazole orally b. Use vancomycin orally c. Sigmoidoscopy and treat only if pseudomembranes are found d. Intravenous metronidazole e. Wait for stool culture f. Intravenous vancomycin MTB S2CK  ‐ p. 256  Only if patient cannot take orally Not necessary C. diff. doesn’t grow in culture Repeat metronidazole before switching / IV vancomycin does not work Repeat metronidazole before switching Diarrhea/Antibiotic Associated  Yes Diarrhea after antibiotic Use C. difficile positive? YesNo Consider T t ithConsider alternative causes Treat with metronidazole Continue metronidazole until end of course Switch to oral vancomycin or fidaxomicin No Yes Improvement? 16 Diarrhea/Malabsorption  All present with steatorrhea: • Oily • Greasy • Floating • Foul smelling Stools Causes: • Celiac disease • Whipple’s disease • Chronic pancreatitis MTB S2CK  ‐ p. 256 • All forms of fat malabsorption present with deficiency of fat-soluble vitamins (A, D, E, and K) • Hence, they can all present with... Diarrhea/Malabsorption  Vitamin D Deficiency Hypocalcemia Manifestation MTB S2CK  ‐ p. 256‐257 Vitamin B12 needs an intact bowel wall and pancreatic enzymes to be absorbed Vitamin K Vitamin B12 Bleeding, easy bruising Anemia, hypersegmented  neutrophils, neuropathy Diarrhea/Diagnostic Tests Celiac disease • Best initial test is... – Anti-tissue transglutaminase Most accurate diagnostic test is... – Small bowel biopsy • Flattening of villi MTB S2CK  ‐ p. 257 Source: commons.wikimedia.org • Flattening of villi • Can exclude lymphoma Other tests • IgA antigliadin antibody • Antiendomysial antibody Diarrhea/Malabsorption  Whipple’s Disease • Arthralgias • Ocular findings • Neurologic abnormalities (dementia, seizures) • Fever L h d th• Lymphadenopathy MTB S2CK  ‐ p. 257 Diarrhea/Malabsorption  Whipple’s disease and tropical sprue • Most accurate diagnostic test is... – Bowel wall biopsy showing specific organism – Treat with ceftriaxone or TMP/SMZ MTB S2CK  ‐ p. 257 Source: commons.wikimedia.org Chronic Pancreatitis/Diagnostic Tests  Abdominal X-ray • 50% to 60% sensitive for calcification of pancreas and very specific when test is abnormal MTB S2CK  ‐ p. 257‐258 17 Chronic Pancreatitis/Diagnostic Tests  Abdominal CT scan • 80% to 90% sensitive for pancreatic calcification MTB S2CK  ‐ p. 257‐258 Chronic Pancreatitis/Diagnostic Tests  Secretin stimulation testing • Most accurate diagnostic test – Place NG tube; normal pancreas releases large volume of bicarbonate-rich fluids after IV secretin D-xylose testing • Old test to distinguish pancreatitis from bowel wallOld test to distinguish pancreatitis from bowel wall abnormalities • D-xylose normal in pancreatic disorders MTB S2CK  ‐ p. 257‐258 Malabsorption/Treatment Disease  Specific Treatment Chronic pancreatitis Celiac disease Enzyme replacement Avoid gluten‐containing  foods (wheat, oats, rye,  barley) MTB S2CK  ‐ p. 258 Whipple’s disease Tropical sprue barley) Ceftriaxone, TMP/SMX TMP/SMX, tetracycline Carcinoid Syndrome  Presentation • Flushing • Wheezing • CV murmurs – tricuspid regurgitation • Diarrhea Best initial diagnostic test is... • Urinary 5-hydroxyindoleacetic acid (5-HIAA) test Treatment • Octreotide MTB S2CK  ‐ p. 258‐259 Lactose Intolerance  • Presents like malabsorptive diarrhea, except... – Intermittently – No weight loss – Normal vitamin levels • Best initial diagnostic test is... – Stool osmolality test • Most accurate test is... – Cessation of symptoms after diet change • Best treatment is... – Stop eating milk products and consider exogenous lactase therapy MTB S2CK  ‐ p. 259 Irritable Bowel Syndrome (IBS) • Pain syndrome with either diarrhea, constipation, or both • Pain of IBS is... – Relieved by BM – Less at night – Relieved by a change in bowel habit (e.g., diarrhea)Relieved by a change in bowel habit (e.g., diarrhea) • No specific diagnostic test – Diagnosis of exclusion in association with complex of symptoms • Not associated with... – Weight loss – Blood or white cells in stool MTB S2CK  ‐ p. 259 18 Irritable Bowel Syndrome/Treatment  • Fiber in diet • Antispasmodic agents – Hyoscyamine – Dicyclomine • Tricyclic antidepressantsy p – Amitriptyline • Antimotility agents – Loperamide for diarrhea – Lubiprostone (chloride-channel activator) • Increases BM frequency MTB S2CK  ‐ p. 259 Inflammatory Bowel Disease  Crohn’s disease (CD) and ulcerative colitis (UC) present with... • Diarrhea and abdominal pain • Blood in stool  anemia • Weight lossg • Fever MTB S2CK  ‐ p. 259 Inflammatory Bowel Disease  Extraintestinal manifestations in both CD and UC • Arthralgias • Uveitis, iritis • Skin manifestation (erythema nodosum, pyoderma gangrenosum) • Sclerosing cholangitis (more frequent in UC)• Sclerosing cholangitis (more frequent in UC) Risk of cancer associated with CD and UC • Both forms of IBD can lead to colon cancer • Cancer risk  with duration • CD involving colon has same cancer risk as UC MTB S2CK  ‐ p. 259‐260 Inflammatory Bowel Disease  Erythema Nodosum Pyoderma Gangrenosum Source: commons.wikimedia.orgSource: commons.wikimedia.org Inflammatory Bowel Disease/Differences  Crohn’s disease Ulcerative colitis Skip lesions Transmural granulomas Fistulas and granulomas Masses and obstruction Curable by surgery Entirely mucosal No fistulas, no abscesses No obstruction MTB S2CK  ‐ p. 260 Perianal disease No perianal disease Frequent question: When should screening occur? Answer: After 8 to 10 years of colonic involvement,  with colonoscopy every 1 to 2 years. Inflammatory Bowel Disease/Diagnostic Tests  • Most accurate test is... – Endoscopy • CD that’s mainly in small bowel, radiologic tests such as barium studies will detect lesions MTB S2CK  ‐ p. 260 Source: commons.wikimedia.orgSource: commons.wikimedia.org 19 Inflammatory Bowel Disease/Diagnostic Tests  Antineutrophil cytoplasmic  antibody (ANCA) Negative Positive Test Crohn’s disease Ulcerative colitis ANCA and ASCA Results in IBD MTB S2CK  ‐ p. 260 Antisaccharomyces  cerevesiae antibody (ASCA) Positive Negative Inflammatory Bowel Disease/Treatment • Acute exacerbations of either CD or UC are treated with steroids • Chronic maintenance of remission is with 5- ASA derivatives (mesalamine) • Asacol for UC • Pentasa for CD • Perianal CD – Ciprofloxacin and metronidazole MTB S2CK  ‐ p. 260‐261 Inflammatory Bowel Disease/Treatment • Azathioprine and 6-mercaptopurine are used to wean patients off steroids Fistulae and severe unresponsive disease • Anti-tumor necrosis factor (TNF) agents (infliximab) • Surgery only if there’s no response to anti-TNF agentsagents NOTE • Neither form of IBD is routinely treated with surgery • UC can be cured, however, with colectomy • In CD, surgery is used exclusively for bowel obstruction as it recurs at surgical site MTB S2CK  ‐ p. 261 Diverticulosis • Outpocketings of colon – Where arteries meet mucosa • Vegetarians • At risk? • AsymptomaticAsymptomatic • Infection? MTB S2CK  ‐ p. 261 Diverticulosis • Most accurate test is... – Colonoscopy • Barium studies • Fiber Fiber Fiber MTB S2CK  ‐ p. 261 Source: commons.wikimedia.org Diverticulitis Diagnosis • LLQ pain and tenderness • Fever • Leukocytosis • Palpable mass sometimes occursPalpable mass sometimes occurs • Symptoms such as nausea, constipation, and bleeding can be present, but are nonspecific MTB S2CK  ‐ p. 261 20 Diverticulitis • Best initial test is... – CT scan of the abdomen – 98% accuracy • Colonoscopy and barium enema are dangerous in acute diverticulitis g – Increased risk of perforation because infection weakens colonic wall MTB S2CK  ‐ p. 261 Diverticulitis Source: commons.wikimedia.org Diverticulitis/Treatment Treatment • Antibiotics that cover E. coli and anaerobes that are present in bowel such as... – Ciprofloxacin combined with metronidazole – Amoxicillin/clavulanate – Ticarcillin/clavulanateTicarcillin/clavulanate – Piperacillin/tazobactam • Surgery is for those with... – No response to medical therapy – Frequent recurrences of infection – Perforation, fistula formation, abscess, strictures, or obstruction MTB S2CK  ‐ 261‐262 Which of the following is the most effective method of screening for colon cancer? a. Colonoscopy b. Sigmoidoscopy c. Fecal occult blood testing (FOBT) d Barium enema  All less sensitive than colonoscopy d. Barium enema e. Virtual colonoscopy with CT scanning f. Capsule endoscopy MTB S2CK  ‐ p. 262 For small bowel bleeding Low sensitivity; misses small polyps Colon Cancer/Frequency of Screening   Routine testing • Patients should have a colonoscopy every 10 years beginning at age 50 Single family member with colon cancer?g y • Begin 10 years earlier than the age at which the family member developed their cancer or age 40, whichever is younger • Screen every 10 years if relative > 60 or every 5 years if relative < 60 MTB S2CK  ‐ p. 262 Colon Cancer/Frequency of Screening   Hereditary nonpolyposis colon cancer syndrome (HNPCC) comprises... • 3 family members • 2 generations • 1 premature (< 50)p ( ) • Start screening at age 25 with colonoscopy every 1 to 2 years MTB S2CK  ‐ p. 262 21 Colon Cancer/Frequency of Screening Familial adenomatous polyposis (FAP) • Presence of thousands of polyps with abnormal genetic test known as adenomatous polyposis coli (APC) test • Start screening with sigmoidoscopy at age 12 every year MTB S2CK  ‐ p. 263 Colon Cancer/Frequency of Screening Previous adenomatous polyp • Patient should have colonoscopy... – Every 3 to 5 years Previous history of colon cancerPrevious history of colon cancer • Patient should have colonoscopy... – 1 year after resection – Then at 3 years – Then every 5 years MTB S2CK  ‐ p. 263 Other Polyposis Syndromes    Peutz-Jeghers syndrome • Multiple hamartomatous polyps, melanotic spots on lips and skin,  frequency of breast cancer,  gonadal and pancreatic cancer Gardner syndrome • Colon cancer associated with: osteomas, desmoid tumors, and other soft tissue tumors Turcot syndrome • Colon cancer in association with CNS malignancy Juvenile polyposis • Colon cancer in association with multiple hamartomatous polyps MTB S2CK  ‐ p. 263 Pancreas & Liver Acute Pancreatitis  Drug toxicity Drug allergy Scorpion Most common 1. GB stones 2. ETOH MTB S2CK  ‐ p. 263‐264 Pancreatitis Trauma Infection Hypertriglyceridemia Hypercalcemia Ductal obstruction sting Acute Pancreatitis/Presentation  Acute epigastric pain + tenderness + nausea/vomiting = Pancreatitis • Pain intensity is subjective and doesn’t correlate with degree of organ damagewith degree of organ damage • In severe cases there’s hypotension and fever The pain of pancreatitis goes straight through to the back “like a spear” stabbed into the abdomen. Cholecystitis pain goes around the side to the back. MTB S2CK  ‐ p. 264 22 Which of the following is associated with the worst prognosis in pancreatitis? a. Elevated amylase b. Elevated lipase c. Intensity of the pain d Low calcium Levels do not correlate with severity Pain doesn’t predict d. Low calcium e. C-reactive protein (CRP) rising MTB S2CK  ‐ p. 264  Elevated with all inflammation Acute Pancreatitis/Diagnostic Tests   • Best initial tests are... – Amylase and lipase • Most specific diagnostic test is – CT scan Labs • CBC: leukocytosis, drop in Hct over time withCBC: leukocytosis, drop in Hct over time with rehydration • Elevated LDH and AST • Hypoxia • Hypocalcemia • Elevated urinary trypsinogen activation peptide MTB S2CK  ‐ p. 264‐265 Acute Pancreatitis/Diagnostic Tests   Imaging • CT or MRI scan are best – Also detect pseudocysts • ERCP – Can help determine etiology (stones, stricture, tumor) • Plain X ray• Plain X-ray – Sentinel loop of bowel (air-filled piece of small bowel in LUQ) – Limited utility • Ultrasound has very poor accuracy – Overlying bowel blocks precise imaging MTB S2CK  ‐ p. 265 Acute Pancreatitis/Diagnostic Tests   NOTE: Abdominal CT scan is always performed with IV and oral contrast to better define and outline abdominal structures. Source: Niket Sonpal, MD Acute Pancreatitis/Treatment • NPO (no food) • IV hydration • Analgesia • PPIs  pancreatic stimulation from acid entering duodenum g MTB S2CK  ‐ p. 265 Acute Pancreatitis/Treatment • > 30% necrosis on CT or MRI, add antibiotics (e.g., imipenem) • Infected, necrotic pancreatitis should be resected with surgical debridement to prevent ARDS and death • Pseudocysts are drained with a needle if they are enlarging or painful MTB S2CK  ‐ p. 265 23 Acute Pancreatitis/Complication   Source: commons.wikimedia.org Liver Disease Chronic Li Coagulopathy Spider angiomata and palmar erythema Asterixis and h l th Portal hypertension leading to varices MTB S2CK  ‐ p. 265 Liver Disease Hepatopulmonary syndrome Hypoalbuminemia & edema and ascitesThrombocytopenia Hepatorenal syndrome encephalopathy Paracentesis is performed with... • New-onset ascites • Abdominal pain and tenderness • Fever L lb i i th iti fl id? Ascites Low albumin in the ascitic fluid? • Portal HTN from cirrhosis is the etiology Serum ascites albumin gradient (SAAG) • The difference or “gradient” of albumin between serum and ascitic fluid MTB S2CK  ‐ p. 266 Ascites  1.1 g/dL Infections Cancer Portal HTN CHF SAAG: Correlating Level with Specific Diseases MTB S2CK  ‐ p. 266 Cancer Nephrotic syndrome CHF Hepatic vein thrombosis Constrictive pericarditis Spontaneous Bacterial Peritonitis • Infection without perforation of bowel • Causative organisms – E. coli (most common) – Other gram-negative bacilli Pneumococcus– Pneumococcus – Anaerobes (rare) MTB S2CK  ‐ p. 266 Spontaneous Bacterial Peritonitis Best initial test is... • Cell count with > 250 neutrophils Most accurate test is... • Fluid culture, but takes too long for results G t i i ti /LDH ifi• Gram stain is negative/LDH nonspecific • Treatment: cefotaxime or ceftriaxone • NOTE: SBP frequently recurs. When the ascites fluid albumin level is quite low, use prophylactic norfloxacin or TMP/SMX. MTB S2CK  ‐ p. 266 24 Treatment of Specific Features of Cirrhosis  Feature Treatment Ascites and edema Coagulopathy and  thrombocytopenia Encephalopathy lb Spironolactone and other diuretics. Serial  pericentesis for large‐volume ascites. FFP and/or platelets only if bleeding occurs Lactulose, neomycin, or rifaximin f h MTB S2CK  ‐ p. 267 Hypoalbuminemia Spider angiomata and palmar  erythema Varices Hepatorenal syndrome Hepatopulmonary syndrome No specific therapy No specific therapy Propranolol and banding via endoscopy Somatostatin (octreotide), midodrine No specific therapy Alcoholic Liver Disease • Diagnosis of exclusion • No specific therapy • Most accurate test is... – Liver biopsy MTB S2CK  ‐ p. 267 Alcohol and drugs causing liver disease give a greater elevation in AST compared to ALT. Viral hepatitis: Higher ALT than AST. Binge drinking: Sudden rise in GGTP. Source: commons.wikimedia.org Primary Biliary Cirrhosis (PBC) PBC is “most likely diagnosis” with... • Woman in 40s or 50s • Fatigue and itching • Normal bilirubin • Elevated alkaline phosphatase MTB S2CK  ‐ p. 267 Primary Biliary Cirrhosis (PBC) Most unique features of PBC are... • Xanthelasma/xanthoma • Osteoporosis Most accurate test is... • Liver biopsyLiver biopsy Most accurate blood test: • Antimitochondrial antibody Treatment with... • Ursodeoxycholic acid MTB S2CK  ‐ p. 267‐268 Primary Biliary Cirrhosis (PBC) Source: commons.wikimedia.org Primary Sclerosing Cholangitis  • Pruritus • Elevated alkaline phosphatase • GGTP • Elevated bilirubin level Treatment • Cholestyramine • Ursodeoxycholic acid Most accurate test is... • ERCP, not liver biopsy • Shows beading, narrowing, or strictures in biliary system MTB S2CK  ‐ p. 268 Source: commons.wikimedia.org 25 Primary Sclerosing Cholangitis  PSC doesn’t improve or resolve with resolution of IBD. Even after a colectomy in UC, patient may still progress to needing a liverstill progress to needing a liver transplantation. MTB S2CK  ‐ p. 268 Alpha 1‐Antitrypsin Deficiency  Look for... • Combination of... – Liver disease – Emphysema (COPD) • Young patient (< 40) • Nonsmoker• Nonsmoker Treatment • Replace enzyme exogenously MTB S2CK  ‐ p. 268 Hemochromatosis  • Genetic disorder leading to overabsorption of iron in duodenum • Mutation: C282y gene • Presentation – Patient in their 50s with mild increases in AST and alkaline phosphatase MTB S2CK  ‐ p. 268 Hemochromatosis  Hemochromatosis Skin Darkening Amenorrhea Erectile MTB S2CK  ‐ p. 268‐269 Fatigue and joint pain (pseudogout) Cardiomegaly Hemochromatosis Diabetes dysfunction Hemochromatosis  Best initial test is... • Iron studies – Increased serum iron and ferritin – Decreased iron binding capacity EKG • Conduction defects Echocardiogram • Dilated or restrictive cardiomyopathy Most accurate test is... • Liver biopsy – Increased iron cardiomyopathy Best therapy • Phlebotomy MTB S2CK  ‐ p. 269 Chronic Hepatitis B and C   Both are associated with... • Cirrhosis • Liver cancer • PAN MTB S2CK  ‐ p. 269 26 Chronic Hepatitis B and C   Chronic hepatitis B • Surface antigen positive > 6 months • Hepatitis B DNA PCR is the best way to determine viral Chronic hepatitis C • 80% have chronic infection • Never symptomatic when illness contracted • Hepatitis C DNA PCR replication activity • Liver biopsy for fibrosis • Biopsy tracks progress Hepatitis C DNA PCR – Determines disease activity MTB S2CK  ‐ p. 270 Chronic Hepatitis B and C/Treatment   Chronic hepatitis B • Adefovir • Lamivudine • Telbivudine • Entecavir T f i Chronic hepatitis C Combination of... Interferon + Ribavirin + Telapavir ( B i )• Tenofovir • Interferon (or Boceprevir) MTB S2CK  ‐ p. 270 Hepatitis Treatment Side Effects Drug Adverse Effects Interferon Ribavarin Adefovir Arthralgias, thrombocytopenia,  depression, leukopenia Anemia Renal dysfunction MTB S2CK  ‐ p. 270 Adefovir Lamivudine Bocepevir Telaprevir Renal dysfunction None Anemia Rash Wilson Disease/Presentation  • Decrease in ceruloplasmin causes buildup of copper • Neurological symptoms – Psychosis, tremor, dysarthria, ataxia, or seizures • Coombs negative hemolytic anemia • Renal tubular acidosis or nephrolithiasis MTB S2CK  ‐ p. 270‐271 Wilson Disease/Diagnosis  Best initial test is... • Slit-lamp examination for Kayser-Fleischer rings Most accurate diagnostic test is... g • Abnormally increased amount of copper excretion into urine after giving penicillamine MTB S2CK  ‐ p. 271 Wilson Disease MTB S2CK  ‐ p. 271 27 Wilson Disease/Treatment • Penicillamine chelates copper and removes it Additional therapies are... • Zinc: interferes with intestinal copper absorption • Trientine: alternate copper-chelating compound MTB S2CK  ‐ p. 271 Decreased ceruloplasmin level is not the most accurate test. This is the most common wrong answer. All plasma proteins can be decreased in those with liver dysfunction and cirrhosis. Autoimmune Hepatitis  Look for... • Young women • Signs of liver inflammation • Positive ANA Most accurate test: • Liver biopsy Treatment • Prednisone and/or azathioprine More specific tests: • Liver-kidney microsomal antibodies • Anti-smooth muscle antibodies azathioprine MTB S2CK  ‐ p. 271 Autoimmune Hepatitis  Source: commons.wikimedia.org Nonalcoholic Steatohepatitis  Nonalcoholic Fatty Liver Disease • Extremely common cause of mildly abnormal liver function tests Disorder is associated with: • Obesity• Obesity • Diabetes • Hyperlipidemia • Corticosteroid use • Most accurate test: biopsy • Management: weight loss MTB S2CK  ‐ p. 272 Nonalcoholic Steatohepatitis  Source: commons.wikimedia.org 1 Hematology Dr. Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Anemia Presentation Diagnostic Tests Symptomsy p Mean Corpuscular Volume • Microcytic Anemia • Macrocytic Anemia • Normocytic Anemia Treatment Anemia Presentation • All forms of anemia present with identical symptoms if they have the same hematocrit (Hct) • Symptoms based on severity, not etiology • “What is the most likely diagnosis?” – Cannot be answered using symptoms alone– Cannot be answered using symptoms alone Diagnostic Tests • Best initial test to evaluate anemia? – Always a complete blood count (CBC) MTB S2CK  ‐ p. 203 Hematocrit and Symptoms Hematocrit Expected Symptoms > 30 – 35%  25 – 30%  None Dyspnea (worse on  exertion), fatigue MTB S2CK  ‐ p. 203 20 – 25% 2 Microcytosis Causes of low MCV: • Iron deficiency • Thalassemia • Sideroblastic anemia • Anemia of chronic disease MTB S2CK  ‐ p. 204 Microcytosis Similarities among microcytic anemias • Low reticulocyte count • Only alpha thalassemia has 3 genes deleted  elevated reticulocyte count • Microcytic anemias are due to production problems MTB S2CK  ‐ p. 204 problems – Nearly synonymous with  reticulocyte counts Microcytosis Routine blood smear • Not effective in telling the difference between types of microcytosis – All hypochromic – All potentially give target cells MTB S2CK  ‐ p. 204 Causes of high MCV • B12 & folate deficiency • Alcoholism • Sideroblastic anemia • Liver disease or hypothyroidism M di ti ( id di h t i ) Macrocytic Anemia/Etiology • Medications (e.g., zidovudine or phenytoin) • Antimetabolite medications: azathioprine, 6- mercaptopurine, hydroxyurea • Myelodysplastic syndrome (MDS) MTB S2CK  ‐ p. 204 Normocytic Anemia • Acute blood loss & hemolysis  rapid drop in Hct (no time for MCV change) • Blood loss leads to iron deficiency & microcytosis • Hemolysis increases reticulocyte count – Reticulocytes raise the MCV – Reticulocytes slightly larger than normal cells MTB S2CK  ‐ p. 204 Reticulocytes slightly larger than normal cells Anemia/Treatment Treatment • If severe: give packed RBCs • Answering the question “At what Hct do I transfuse a patient?” depends on the following factors: 1. Symptomatic? Transfuse.1. Symptomatic? Transfuse. 2. Hct very low in elderly person? Heart disease? Transfuse. MTB S2CK  ‐ p. 205 3 Anemia/Treatment  “Symptomatic” from anemia means: • SOB • Lightheaded, confused, and sometimes syncope • Hypotension and tachycardia • Chest pain MTB S2CK  ‐ p. 205 Remember: No transfusion if young & asymptomatic Blood Products Packed Red Blood Cells (PRBCs) • Concentrated form of blood • Whole blood - 150 mL plasma = PRBCs • Hct of PRBCs: 70% - 80% • Removal of plasma doubles Hct • Each unit PRBCs raises Hct by 3 points/unit MTB S2CK  ‐ p. 205 Blood Products Fresh Frozen Plasma (FFP) • Replaces clotting factors for elevated prothrombin time, aPTT, or INR • Most important if actively bleeding • FFP used as replacement with plasmapheresis MTB S2CK  ‐ p. 205 Blood Products Cryoprecipitate • Used to replace fibrinogen • Some utility in disseminated intravascular coagulation (DIC) • Provides high amounts of clotting factors in small plasma volumeplasma volume • Whole blood is never correct • Whole blood is divided into either PRBCs or FFP MTB S2CK  ‐ p. 205 Microcytic Anemia Etiology Presentation Diagnostic TestsDiagnostic Tests Treatment Microcytic Anemia Microcytosis = MCV < 80 fL MTB S2CK  ‐ p. 206 Microcytic, hypochromic anemia seen on blood smear. Copyright James Van Rhee.   Used with permission.  4 Microcytic Anemia/Etiology Iron deficiency • Blood loss • One teaspoon (5 mL/day) blood loss leads to iron deficiency over time • Body only needs very tiny amount of iron – 1 to 2 mg/day– 1 to 2 mg/day • Menstruating women need a little more – 2-3 mg/day • Pregnant women need 5-6 mg/day • Duodenum absorbs only about 4 mg/day MTB S2CK  ‐ p. 206 Microcytic Anemia/Etiology Chronic disease • Initially MCV is normal, then decreases • Unclear etiology • Any cancer or chronic infection • Clear mechanism only in renal failure deficiency of erythropoietinerythropoietin • Hemoglobin synthesis will not occur because iron does not move forward • Iron is locked in storage or trapped in macrophages or in ferritin MTB S2CK  ‐ p. 206 Microcytic Anemia/Etiology Sideroblastic anemia • Can be macrocytic when associated with myelodysplasia (MDS) • Most common cause: Alcohol effect on marrow • Less common causes... – Lead poisoning– Lead poisoning – Isoniazid – Vitamin B6 deficiency MTB S2CK  ‐ p. 206 Microcytic Anemia/Etiology Thalassemia • Extremely common cause of microcytosis • Most with thalassemia trait are asymptomatic MTB S2CK  ‐ p. 206 Microcytic Anemia/Presentation • You can’t distinguish these anemias based on symptoms • Might have a suggestion from history MTB S2CK  ‐ p. 206 How to answer “What is the most likely diagnosis? for anemia Microcytic Anemia/Presentation Feature in the History Most likely diagnosis? Blood loss (GI bleeding) Menstruation Iron deficiency Iron deficiency MTB S2CK  ‐ p. 206 Menstruation Cancer or chronic infection Rheumatoid arthritis Alcoholic Asymptomatic Iron deficiency Chronic disease Chronic disease Sideroblastic Thalassemia 5 Microcytic Anemia/Diagnostic Tests  • Peripheral smear not useful! • All hypochromic • All can be associated with target cells MTB S2CK  ‐ p. 207 Microcytic Anemia/Diagnostic Tests  • Target cells: most common with thalassemia MTB S2CK  ‐ p. 207 Copyright James Van Rhee.   Used with permission.  Microcytic Anemia/Iron Studies Unique features and diagnoses of iron studies Unique Feature Diagnosis Low ferritin High iron Iron deficiency Sideroblastic anemia MTB S2CK  ‐ p. 207 Normal iron studies Thalassemia Microcytic Anemia/Iron Studies Iron deficiency • Low ferritin = Iron deficiency • However, one third of patients with iron deficiency will have normal or increased ferritin – Ferritin is an “acute phase reactant” • This means any infection or inflammation can raise the ferritin level MTB S2CK  ‐ p. 207 Microcytic Anemia/Iron Studies • Both iron deficiency and anemia of chronic disease are associated with low serum iron • Iron deficiency: increase in total iron binding capacity (TIBC) • TIBC measures unbound sites on transferrin • Open sites on transferrin = increased “capacity” or MTB S2CK  ‐ p. 207 Open sites on transferrin increased capacity or number of unbound sites Microcytic Anemia/Iron Studies Chronic disease • Serum iron: low in circulation • Iron trapped in storage • Ferritin (stored iron): elevated or normal • Circulating iron: decreased M j diff i TIBC i l MTB S2CK  ‐ p. 207 • Major difference is TIBC is low 6 Microcytic Anemia/Iron Studies Sideroblastic anemia • Only microcytic anemia elevated circulating iron level Thalassemia • Genetic disease with normal iron studies• Genetic disease with normal iron studies MTB S2CK  ‐ p. 207 Unique Laboratory Features  Iron deficiency • Red cell distribution of width (RDW) increased – Newer cells are more iron deficient – Newer cells are smaller in iron deficiency – As body runs out of iron, newer cells have less Hb & get progressively smallerg p g y • Elevated platelet count common • Single most accurate test is... – Bone marrow biopsy for stainable iron (decreased) – Rarely done, but most accurate MTB S2CK  ‐ p. 207 Unique Laboratory Features  Sideroblastic anemia The most accurate test is... • Prussian blue staining for ringed sideroblasts • Basophilic stippling can occur in any cause ofoccur in any cause of sideroblastic anemia MTB S2CK  ‐ p. 207‐208 Unique Laboratory Features  Thalassemia • Most accurate test is... Hb electrophoresis! MTB S2CK  ‐ p. 208 Source: commons.wikimedia.org Unique Laboratory Features  Thalassemia • Most accurate test for alpha thalassemia – Genetic studies – 3-gene deletion alpha thalassemia • Hb H (beta-4 tetrads) • Increased reticulocyte countIncreased reticulocyte count • All thalassemia types have normal RDW MTB S2CK  ‐ p. 208 Electrophoresis Findings Alpha thalassemia Beta thalassemia One gene deleted: normal Two genes deleted: mild anemia,  normal electrophoresis Three genes deleted: moderate Inc. Hb F and A2 N/A Beta thalassemia intermedia MTB S2CK  ‐ p. 208 Three genes deleted: moderate  anemia with Hb H (beta 4  tetrads), increased reticulocytes Four genes deleted: gamma 4  tetrads or hemoglobin Bart; CHF  causes death in utero Beta thalassemia intermedia • Normal Hb F • No transfusion dependence N/A 7 Microcytic Anemia/Treatment Iron deficiency • Replace iron with oral ferrous sulfate • If insufficient, patients get IM iron Chronic disease • Correct underlying disease O l d t l f il d t• Only end-stage renal failure responds to erythropoietin Sideroblastic anemia • Correct the cause • Some respond to vitamin B6 (pyridoxine) MTB S2CK  ‐ p. 208 Microcytic Anemia/Treatment Thalassemia • Trait not treated Beta thalassemia major (Cooley anemia) • Chronic transfusion lifelong I l d d ith d f i ( l i• Iron overload managed with deferasirox (oral iron chelator) • Deferoxamine is parenteral MTB S2CK  ‐ p. 209 Macrocytic Anemia Etiology Presentation Diagnostic TestsDiagnostic Tests Treatment 73-year-old man in office with fatigue progressively worse over several months. He is short of breath when he walks up one flight of stairs. He drinks 4 vodka martinis a day. He complains of numbness and tingling in his feet. Physical: decreased sensation in feet. Hct: 28% MCV: 114 fL (elevated) What is the next step?1st is peripheral smearWhat is the next step? a. Vitamin B12 level b. Folate level c. Peripheral blood smear d. Schilling test e. Methylmalonic acid level MTB S2CK  ‐ p. 209  To see if B12 deficiency is due to pernicious anemia Confirms diagnosis of B12 deficiency when B12 levels are equivocal Once hypersegmented neutrophils are seen, THEN get B12 & folate levels Macrocytic Anemia  Megaloblastic Hypersegmented neutrophils • Many factors raise MCV • Only B12 & folate deficiency & MTB S2CK  ‐ p. 209‐210 Source: Alireza Eghtedar, MD antimetabolite medications cause hypersegmentation Vitamin B12 deficiency is caused by... • Pernicious anemia • Pancreatic insufficiency • Dietary deficiency (vegan/strict vegetarian) • Crohn’s disease damaging terminal ileum • Blind loop syndrome (gastrectomy or gastric Macrocytic Anemia/Etiology  Blind loop syndrome (gastrectomy or gastric bypass for weight loss) • Diphyllobothrium latum MTB S2CK  ‐ p. 209 8 Macrocytic Anemia/Etiology  Folate deficiency • Dietary deficiency (goat’s milk has no folate and limited iron/B12) • Psoriasis & skin loss or turnover • Drugs: phenytoin, sulfa g p y , MTB S2CK  ‐ p. 209 Macrocytic Anemia/Presentation Alcohol • Gives macrocytosis & neurological problems • Will not give hypersegmented neutrophils MTB S2CK  ‐ p. 209 Macrocytic Anemia/Presentation B12 deficiency • Can give any neurological abnormality • Peripheral neuropathy most common • Dementia least common • Posterior column damage to position & vibratory sensation or “subacute combined degeneration” ofsensation or subacute combined degeneration of cord is classic • Look for ataxia MTB S2CK  ‐ p. 210 Macrocytic Anemia/Diagnostic Tests   Labs common to both B12 & folate deficiency • Megaloblastic anemia • Increased LDH & indirect bilirubin levels • Decreased reticulocyte count • Hypercellular bone marrow M l t• Macroovalocytes • Increased homocysteine levels • Only B12 deficiency is associated with increased methylmalonic acid level MTB S2CK  ‐ p. 210 Macrocytic Anemia/Diagnostic Tests   B12 & folate deficiency • Identical hematologically on blood smear MTB S2CK  ‐ p. 210 Source: Alireza Eghtedar, MD 73-year-old woman with decreased position & vibratory sensation of lower extremities. Hct: 28%, MCV: 114 fL, and hypersegmented neutrophils. B12 level decreased, but near the borderline of normal. What is the next step in management? a. Methylmalonic acid level  Confirms cause as pernicious b. Anti-intrinsic factor antibodies c. Anti-parietal cell antibodies d. Schillings test e. Folate level f. Homocysteine level MTB S2CK  ‐ p. 210‐211 Folate doesn’t give neurological deficits Doesn’t add anything Rare test of etiology; premature anemia after B12 deficiency confirmed 9 Macrocytic Anemia/Diagnostic Tests   Tested facts about macrocytic anemia • Schilling test is never the right answer • Pernicious anemia is confirmed with anti- intrinsic factor and anti-parietal cell antibodies • Red cells are destroyed as they leave the marrow, so reticulocyte count is low MTB S2CK  ‐ p. 211 Macrocytic Anemia/Diagnostic Tests   Tested facts about macrocytic anemia • B12 & folate deficiency can cause pancytopenia as well as macrocytic anemia • Pancreatic enzymes are needed to absorb B12 – They free it from carrier (R) protein • Neurological abnormalities will improve as long as• Neurological abnormalities will improve as long as they are minor (e.g., peripheral) and short duration MTB S2CK  ‐ p. 211 Macrocytic Anemia/Treatment • Replace what is deficient • Folate replacement corrects hematologic problems of B12 deficiency, but not the neurological problems MTB S2CK  ‐ p. 211 Which of the following is a complication of B12 or folate replacement? a. Seizures b. Hemolysis c Hypokalemia Cells are produced rapidly, not hemolyzed Not associated with treatment c. Hypokalemia d. Hyperkalemia e. Diarrhea MTB S2CK  ‐ p. 211  High K+ from massive tissue or cellular breakdown Cause hypokalemia, but not associated with B12 or folate replacement therapy Hemolytic Anemia – Part 1 Sickle Cell Disease Hereditary Spherocytosis Autoimmune Hemolysisy Hemolytic Anemia  All forms lead to: • Sudden  in Hct • Increased LDH, indirect bilirubin & reticulocytes • Decreased haptoglobin • Slight increase in MCV R ti l t > l ll– Reticulocytes > normal cells • Hyperkalemia MTB S2CK  ‐ p. 211‐212 10 Sickle Cell Disease  • Chronic, well-compensated hemolytic anemia • Reticulocyte count always high • Acute painful vaso-occlusive crisis is caused by... − Hypoxia − Dehydration I f ti− Infection − Cold temperatures MTB S2CK  ‐ p. 212 Sickle Cell Disease/Presentation  Look for... • African American • Sudden, severe pain in chest, back & thighs • May have fever Rare for adult to present with acute crisis without clear history of sickle cell disease MTB S2CK  ‐ p. 212 Sickle Cell Disease/Manifestations  • Bilirubin gallstones • Increased infection from autosplenectomy – Encapsulated organisms • Osteomyelitis • Stroke • Enlarged heart with hyperdynamic features and systolic murmur • Skin ulcers • Avascular necrosis ofy – Most commonly from Salmonella • Retinopathy Avascular necrosis of femoral head MTB S2CK  ‐ p. 212 Sickle Cell Disease/Diagnostic Tests  • Best initial test... - Peripheral smear • Most accurate test.. - Hemoglobin electrophoresiselectrophoresis • Trait (AS disease) does not give sickled cells MTB S2CK  ‐ p. 212‐213 Which is found on smear in sickle cell disease? a. Basophilic stippling b. Howell-Jolly bodies c. Bite cells d S hi t t  Associated with lead poisoning Seen with G6PD deficiency Fragmented red cells seen withd. Schistocytes e. Morulae MTB S2CK  ‐ p. 213 Fragmented red cells seen with intravascular hemolysis Seen inside neutrophils in Ehrlichia infections Sickle Cell Disease/Treatment  1. Oxygen/hydration/analgesia 2. Fever or white cell count higher than usual? Antibiotics given! Ceftriaxone, levofloxacin, or moxifloxacin 3. Folic acid in everyone 4. Pneumococcal vaccine: autosplenectomy4. Pneumococcal vaccine: autosplenectomy 5. Hydroxyurea: prevent recurrences, increases Hb F MTB S2CK  ‐ p. 213 Don’t wait for results of testing! Start antibiotics with fever. No spleen = Overwhelming infection = Death!! 11 Sickle Cell Disease/Treatment  Exchange transfusion for severe vaso- occlusive crisis with: − Acute chest syndrome − Priapism MTB S2CK  ‐ p. 214 − Stroke − Visual disturbance from retinal infarction 43-year-old man with sickle cell disease admitted with acute pain crisis. Only med is folic acid. Hct on admission: 34%. On 3rd hospital day, hematocrit drops to 22%. What is the initial test? a. Reticulocyte count  Not best way to gauge severity ofy b. Peripheral smear c. Folate level d. Parvovirus B-19 IgM level e. Bone marrow MTB S2CK  ‐ p. 214  Causes aplastic crisis which freezes growth of marrow Not best way to gauge severity of hemolysis Marrow shows giant pronormoblasts, but this isn’t better than reticulocyte count at measuring severity of hemolysis Most accurate test for parvovirus B-19 is PCR for DNA. IVIG is best initial therapy. Sickle Cell Trait  • Patient is heterozygous for sickle gene (AS) • Only manifestation is inability to concentrate urine (“isosthenuria”) • Clinically asymptomatic • Normal CBC • Normal smear • Hematuria sometimes occurs • No treatment for sickle cell trait MTB S2CK  ‐ p. 214 Hereditary Spherocytosis  • Genetic defect in cytoskeleton of RBCs • Leads to abnormal round shape • Loss of normal flexibility characteristic of biconcave disc that allows red cells to bend in spleen MTB S2CK  ‐ p. 214‐215 Hereditary Spherocytosis/Presentation  Look for... • Recurrent episodes of hemolysis in a young child or newborn • Intermittent jaundice S l l• Splenomegaly • Family history of anemia or hemolysis • Bilirubin gallstones MTB S2CK  ‐ p. 214‐215 Hereditary Spherocytosis/Diagnosis   • Low MCV • Increased mean corpuscular hemoglobin concentration (MCHC) • Negative Coombs test Most acc rate test Osmotic fragilit• Most accurate test: Osmotic fragility – Cells are placed in slightly hypotonic solution – Increased swelling leads to hemolysis MTB S2CK  ‐ p. 215 12 Hereditary Spherocytosis/Treatment 1. Chronic folic acid replacement supports red cell production 2. Splenectomy stops hemolysis but doesn’t eliminate spherocytes MTB S2CK  ‐ p. 215 Autoimmune Hemolysis  • Also known as warm or IgG hemolysis • Idiopathic in 50% • Clear causes are... − Chronic lymphocytic leukemia (CLL) − Lymphoma − Systemic lupus erythematosus (SLE) − Drugs: penicillin, alpha-methyldopa, rifampin, phenytoin MTB S2CK  ‐ p. 215 Autoimmune Hemolysis/Diagnostic Tests Most accurate diagnostic test is... • Coombs test – Detects IgG on surface of red cells – Direct & indirect tests tell basically the same thing – Indirect associated with greater amount of antibody MTB S2CK  ‐ p. 215‐216 Autoimmune Hemolysis/Diagnostic Tests • Autoantibodies remove small amounts of red cell membrane and lead to smaller membrane • Forces cell to become round • Biconcave discs have greater surface than sphere Smear doesn’t show fragmented cells because destruction occurs inside spleen or liver, not in blood vessel MTB S2CK  ‐ p. 215‐216 Autoimmune Hemolysis/Treatment 1. Glucocorticoids (prednisone) “best initial therapy” 2. Recurrent episodes: splenectomy 3. Severe, acute hemolysis not responding to prednisone can be controlled with intravenous immunoglobulin (IVIG)g ( ) 4. Rituximab when splenectomy doesn’t control hemolysis MTB S2CK  ‐ p. 216 Autoimmune Hemolysis/Treatment Alternate treatments to diminish need for steroids: • Cyclophosphamide • Cyclosporine MTB S2CK  ‐ p. 216 Cyclosporine • Azathioprine • Mycophenolate mofetil 13 Hemolytic Anemia – Part 2 Cold Agglutinin Disease G6PD Deficiency HUS and TTPHUS and TTP PNH Cold Agglutinin Disease IgM antibodies against red cells in association with Epstein-Barr virus, Waldenström macroglobulinemia, or Mycoplasma pneumoniae Presentation • Symptoms in colder parts of body • Numbness or mottling of nose, ears, fingers, and toes • Symptoms resolve on warming body part Diagnosis • Direct Coombs test positive only for complement • Smear normal in most • May show spherocytes MTB S2CK  ‐ p. 216 Cold Agglutinin Disease Treatment 1. Stay warm 2. Administer rituximab 3. Cyclophosphamide, cyclosporine, or other immunosuppressive agents stop production of antibodyantibody 4. Plasmapheresis in some Steroids and splenectomy usually don’t work MTB S2CK  ‐ p. 216‐217 Cold Agglutinin Disease/Treatment Cryoglobulins often mixed up with cold agglutinins. Both are IgM and don’t respond to steroids. Cryoglobulins are associated with: • Hepatitis C • Joint pain MTB S2CK  ‐ p. 217 Joint pain • Glomerulonephritis G6PD Deficiency  • X-linked recessive • Inability to generate glutathione reductase and protect red cells from oxidant stress • Most common oxidant stress is infection • Other causes: dapsone, quinidine, sulfa drugs, primaquine nitrofurantoin and fava beansprimaquine, nitrofurantoin, and fava beans MTB S2CK  ‐ p. 217 G6PD deficiency is X-linked recessive, it manifests almost exclusively in males G6PD Deficiency/Presentation  Look for... • African American or Mediterranean males • Sudden anemia & jaundice • Normal-sized spleen With i f ti d• With infection or drug MTB S2CK  ‐ p. 217 14 G6PD Deficiency/Diagnosis  Best initial test is... • Peripheral smear – Look for Heinz bodies and bite cells Most accurate test... • G6PD levelG6PD level – 1 to 2 months after acute episode of hemolysis MTB S2CK  ‐ p. 217 G6PD Deficiency Treatment • Avoid oxidant stress • Nothing reverses hemolysis MTB S2CK  ‐ p. 218 Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are different versions of the same basic disease HUS and TTP HUS • Associated with E. coli 0157:H7 TTP • Associated with ticlopidine clopidogrel0157:H7 • More frequent in children MTB S2CK  ‐ p. 218 ticlopidine, clopidogrel, cyclosporine, and AIDS • Neurological disorders (confusion and seizures) • Fever • More common in adults HUS and TTP Both characterized by: • Intravascular hemolysis with fragmented red cells (schistocytes) • Thrombocytopenia• Thrombocytopenia • Renal insufficiency MTB S2CK  ‐ p. 218 Source: commons.wikimedia.org HUS and TTP Diagnosis • No one specific test diagnoses either disorder • Normal PT/aPTT • Negative Coombs test Treatment • Severe cases treated with plasmapheresis or plasma exchange MTB S2CK  ‐ p. 218 Paroxysmal Nocturnal Hemoglobinuria  • Clonal stem cell defect with increased sensitivity to complement in acidosis Etiology • Deficiency of complement regulatory proteins CD 55 and 59, also known as decay accelerating factor (DAF) • Gene for phosphatidylinositol glycan class A (PIG-A) isGene for phosphatidylinositol glycan class A (PIG A) is defective  overactivation of complement system • During sleep, relative hypoventilation leads to  pCO2 and acidosis • This does nothing to an unaffected person • In PNH it leads to hemolysis and thrombosis MTB S2CK  ‐ p. 218 15 Paroxysmal Nocturnal Hemoglobinuria  Presentation • Episodic dark urine with first urination of day from hemoglobin • Pancytopenia and iron deficiency anemia Thrombosis MCC of death MTB S2CK  ‐ p. 218 Paroxysmal Nocturnal Hemoglobinuria  • Pancytopenia • Most accurate test is... – Decreased CD55 & CD59 • Ham test and sucrose hemolysis are never the correct answer – Flow cytometry is another way of saying CD55/CD59 testing MTB S2CK  ‐ p. 218‐219 Paroxysmal Nocturnal Hemoglobinuria  1. Prednisone 2. Allogeneic bone marrow transplant is the only method of cure 3. Eculizumab inactivates C5 in complement pathway and decreases red cell destruction; it’s a complement inhibitor 4. Folic acid and iron replacement with transfusions as needed MTB S2CK  ‐ p. 219 Hematologic Malignancies Aplastic Anemia Polycythemia Vera Essential ThrombocytosisEssential Thrombocytosis Myelofibrosis Aplastic Anemia  • Pancytopenia of unclear etiology • Any infection or cancer can invade marrow causing decreased production or hypoplasia • Other causes: − Radiation and toxins (e.g., toluene, insecticides (DDT), and benzene) − Drug effect: sulfa, phenytoin, carbamazepine,Drug effect: sulfa, phenytoin, carbamazepine, chloramphenicol, alcohol, chemotherapy − SLE − PNH − Infection: HIV, hepatitis, CMV, EBV − B12 and folate deficiency − Thyroid-inhibiting medications (e.g., propylthiouracil (PTU) and methimazole) MTB S2CK  ‐ p. 219 Aplastic Anemia  • Fatigue of anemia • Infections from low white cell counts • Bleeding from thrombocytopenia Most accurate test isMost accurate test is... • Bone marrow biopsy • Aplastic anemia is confirmed by excluding all causes of pancytopenia MTB S2CK  ‐ p. 219 16 Aplastic Anemia/Treatment • Treat any underlying cause that’s identified THEN... • Blood transfusion, antibiotics for infection, and platelets for bleeding • Aplastic anemia acts as autoimmune disorder MTB S2CK  ‐ p. 219 • Aplastic anemia acts as autoimmune disorder • T cells attack patient’s own marrow • Cyclosporine inhibits T cells  This brings the marrow back to life! Aplastic Anemia/Treatment • True aplastic anemia treated with allogeneic bone marrow transplantation (BMT) if young enough and matched • When too old for BMT (> 50) or no matched donor treatment is anti-thymocyte globulin (ATG) and y y g ( ) cyclosporine • Tacrolimus is alternative to cyclosporine MTB S2CK  ‐ p. 219‐220 Polycythemia Vera  • Unregulated overproduction of all 3 cell lines • Red cell overproduction is most prominent • Mutation in JAK2 protein which regulates marrow production • Red cells grow wildly despite low erythropoietin MTB S2CK  ‐ p. 220 Polycythemia Vera  Symptoms of hyperviscosity from increased red cell mass such as: • Headache, blurred vision, and tinnitus • Hypertension • Fatigue • Splenomegaly• Splenomegaly • Bleeding from engorged blood vessels • Thrombosis from hyperviscosity MTB S2CK  ‐ p. 220 Polycythemia Vera  • You must exclude hypoxia as cause of erythrocytosis • Oxygen levels: normal • Vitamin B12 levels are elevated for unclear reasons • Iron levels  because it’s • Hematocrit markedly elevated > 60% • Platelets and WBC count  • Erythropoietin  • Total red cell mass  Iron levels  because it s been used to make red cells MTB S2CK  ‐ p. 220 Polycythemia Vera  • Most accurate test... –JAK2 mutation (95%) • Increased basophils –All myeloproliferative disorders • Small number converted to AML MTB S2CK  ‐ p. 220 17 Essential Thrombocytosis (ET)  • Markedly elevated platelet count > 1 million • Leads to both thrombosis & bleeding • Very difficult to distinguish from an elevated platelet count as a reaction to another stress (e.g., infection, cancer, or iron deficiency) MTB S2CK  ‐ p. 221 Essential Thrombocytosis (ET)  • < 60 & asymptomatic with platelets < 1.5 million – No treatment necessary • > 60 & thromoboses or platelet count > 1.5 • Best initial therapy... – Hydroxyurea • Anagrelide with red cell suppression from hydroxyurea • Aspirin for million – Begin treatment Aspirin for erythromelalgia (painful, red hands in ET) MTB S2CK  ‐ p. 221 Myelofibrosis  • Older persons with pancytopenia • Bone marrow shows marked fibrosis • Blood production shifts to spleen & liver, which become markedly enlarged • Look for teardrop-shaped cells and nucleated red blood cells on smear • Thalidomide and lenalidomide: tumor necrosis factor inhibitors that increase bone marrow production • Occasional patient < 50-55, allogeneic bone marrow transplantation is attempted MTB S2CK  ‐ p. 221 Leukemia Acute Leukemia Chronic Myelogenous Leukemia Leukostasis Reaction Myelodysplastic Syndrome Chronic Lymphocytic Leukemia Hairy Cell Leukemia Acute Leukemia/Presentation  • History of myelodysplasia suggests acute leukemia • Signs of pancytopenia (fatigue, infection, bleeding) • Even if WBC is normal or increased • Infection is common presentation • Leukemic cells (blasts) don’t function normally MTB S2CK  ‐ p. 221 Acute Leukemia/M3  • Most frequently tested acute leukemia is M3, known as acute promyelocytic leukemia (APL) • M3 is associated with disseminated intravascular coagulation (DIC) “M3  DIC” No distinct clinical presentation bet een the 3• No distinct clinical presentation between the 3 subtypes of acute lymphocytic leukemia (ALL) MTB S2CK  ‐ p. 221 18 Acute Leukemia/Diagnosis  Best initial test is... • Blood smear – Shows blasts Most accurate test is... • Flow cytometry Distinguishes different subtypes of acute leukemia– Distinguishes different subtypes of acute leukemia – Detects specific CD subtypes associated with each type of leukemia Myeloperoxidase • Characteristic of acute myelocytic leukemia (AML) MTB S2CK  ‐ p. 221 Acute Leukemia/Diagnosis  Auer rods • Eosinophilic inclusions • Associated with acute promyelocytic leukemia (M3) MTB S2CK  ‐ p. 221‐222 Acute Leukemia/Treatment   • Both AML & ALL treated initially with chemotherapy to remove blasts from peripheral blood smear • Known as inducing remission • The question is: proceed to BMT after remission or give more chemotherapy • Prognosis poor? go straight to BMTPrognosis poor? go straight to BMT • Prognosis good? more chemotherapy MTB S2CK  ‐ p. 222 Acute Leukemia/Treatment   The best indicator of prognosis in acute leukemia is... Cytogenetics • Assesses specific chromosomal characteristics found in each patient – Good cytogenetics = less chance of relapse = more chemotherapymore chemotherapy – Bad cytogenetics = more chance of relapse = immediate BMT MTB S2CK  ‐ p. 222 Acute Leukemia/Treatment   1. Add all-trans-retinoic acid (ATRA) to those with M3 (acute promyelocytic leukemia) 1. Add intrathecal chemotherapy such as methotrexate to ALL treatment; prevents relapse of ALL in CNS MTB S2CK  ‐ p. 222 Acute Leukemia/Treatment   Most tested facts for acute leukemia are... • M3 (promyelocytic leukemia) gives DIC • Add ATRA to M3 • Auer rods = AMLAuer rods AML • Add intrathecal methotrexate to ALL MTB S2CK  ‐ p. 222 19 Chronic Myelogenous Leukemia/Presentation  Look for... • High WBC count: all neutrophils • Vague symptoms of fatigue, night sweats, and fever from hypermetabolic syndrome • Splenomegaly: early satiety, abdominal fullness, and LUQ painand LUQ pain • Pruritus is common after hot baths/showers – Histamine release from basophils MTB S2CK  ‐ p. 223 Chronic Myelogenous Leukemia/Diagnosis • Determine if it’s a reaction to another infection, stress (leukemoid reaction), or leukemia • CML may give small numbers of blasts • Should be < 5% • Basophils increased MTB S2CK  ‐ p. 223 Chronic Myelogenous Leukemia/Diagnosis   • If leukocyte alkaline phosphatase score (LAP) is a choice, then this is first • Leukemic cells don’t have normal amounts of alkaline phosphatase; LAP score low in CML • If LAP score is not a choice, or the question is “What is the most accurate test?” then answer “BCR-ABL” • Can be done by PCR on peripheral blood MTB S2CK  ‐ p. 223 Chronic Myelogenous Leukemia/Treatment • Imatinib (Gleevec), dasatinib, or nilotinib are the best initial therapy • Only BMT cures CML – Never the first therapy MTB S2CK  ‐ p. 223 54-year-old man with SOB, blurry vision, confusion, and priapism. WBC count 225,000/L. Predominantly neutrophils with about 4% blasts. What is next step in management of this case? a. Leukapheresis b. BCR-ABL testing  In acute leukostasis reaction, i t t t ib. BCR ABL testing c. Bone marrow biopsy d. Bone marrow transplant e. Consult hematology/oncology f. Flow cytometry g. Hydroxyurea MTB S2CK  ‐ p. 223‐224 Will lower the cell count, but not as rapidly as leukapheresis important to remove excessive white cells from the blood than to establish a specific diagnosis, no matter what the etiology Myelodysplastic Syndrome (MDS)  • Preleukemic disorder in those > 60 • Pancytopenia despite hypercellular bone marrow • Most never develop AML • Infection & bleeding lead to death before leukemia occursoccurs MTB S2CK  ‐ p. 224 20 Myelodysplastic Syndrome  • Many present with asymptomatic pancytopenia on routine CBC • Symptoms can be... − Fatigue & weight loss − Infection − Bleeding− Bleeding − Sometimes splenomegaly • No single pathognomonic finding in history or physical examination MTB S2CK  ‐ p. 224 • CBC: anemia with increased MCV, nucleated red cells, and small number of blasts • Marrow: hypercellular • Prussian blue stain shows ringed sideroblasts • Severity based on Myelodysplastic Syndrome/Diagnosis   Severity based on percentage of blasts MTB S2CK  ‐ p. 224‐225 Myelodysplastic Syndrome/Treatment • Transfuse blood products as needed • Erythropoietin: about 20% response • Lenalidomide for those with 5q deletion • Decreases transfusion dependence MTB S2CK  ‐ p. 225 Chronic Lymphocytic Leukemia  • CLL is a clonal proliferation of normal, mature-appearing B lymphocytes that function abnormally • Occurs over age 50 in 90% affected • Most asymptomatic at presentation • Most common symptom is fatigue • Other symptoms: Lymphadenopathy (80%)− Lymphadenopathy (80%) − Spleen or liver enlargement (50%) − Infection MTB S2CK  ‐ p. 225 • No unique physical findings • Richter phenomenon: • Conversion of CLL into high-grade lymphoma • Occurs in 5% Chronic Lymphocytic Leukemia/Diagnosis • WBC usually > 20,000/μL • 80% to 98% lymphocytes • Half are hypogammaglobulinemic • Anemia & thrombocytopenia occurthrombocytopenia occur from marrow infiltration or autoimmune warm IgG antibodies MTB S2CK  ‐ p. 225 Smudge cell: • Lab artifact • Nucleus crushed by cover slip Source: commons.wikimedia.org Chronic Lymphocytic Leukemia/Treatment  • Stage 0 (elevated WBC) & stage I (lymphadenopathy); no treatment • Stage II (hepatosplenomegaly), stage III (anemia), and stage IV (thrombocytopenia) treat with fludarabine • If choices list fludarabine and rituximab, this is the , best initial therapy for advanced-stage disease (II, III, IV) or any patient who is symptomatic (severe fatigue, painful nodes) • PCP prophylaxis is indicated in CLL MTB S2CK  ‐ p. 226 21 • Refractory cases: cyclophosphamide (more efficacy, but more toxic) • Mild cases: chlorambucil • Severe infection: IVIG Chronic Lymphocytic Leukemia/Treatment  • Autoimmune thrombocytopenia or hemolysis: prednisone MTB S2CK  ‐ p. 226 Hairy Cell Leukemia  Middle-aged men with: • Pancytopenia • Massive splenomegaly • Monocytopenia • Inaspirable “dry” tap, despite hypercellularity of marrow The most accurate test is... • Tartrate resistant acid phosphatase (TRAP) or CD11c Treat with cladribine MTB S2CK  ‐ p. 226 Source: commons.wikimedia.org Lymphoma Non‐Hodgkin Lymphoma Hodgkin Disease Multiple MyelomaMultiple Myeloma MGUS Waldenström Macroglobulinemia   Non‐Hodgkin Lymphoma  • Proliferation of lymphocytes in nodes and spleen • NHL most often widespread at presentation • NHL and CLL are extremely similar • NHL is solid mass and CLL is “liquid” or circulating MTB S2CK  ‐ p. 226 Non‐Hodgkin Lymphoma  • Painless lymphadenopathy • May involve pelvic, retroperitoneal, or mesenteric structures • Nodes not warm, red, or tender • “B” symptoms: – Fever weight loss drenching night sweats– Fever, weight loss, drenching night sweats • Advanced stages in 80% to 90% of cases MTB S2CK  ‐ p. 227 Non‐Hodgkin Lymphoma  • Best initial test is... – Excisional biopsy • CBC normal in most cases • High LDH correlates with worse severity • Staging determines intensity of therapy Typical staging procedures are:• Typical staging procedures are: – CT scan of chest, abdomen, and pelvis – Bone marrow biopsy MTB S2CK  ‐ p. 227 22 Non‐Hodgkin Lymphoma  Staging Stage I: 1 lymph node group Stage II: 2+ lymph node groups on same side of diaphragm Stage III: both sides of diaphragm Stage IV: widespread diseaseStage IV: widespread disease Most common wrong answer is needle aspiration of node. Aspiration not enough because individual lymphocytes appear normal. MTB S2CK  ‐ p. 227 Non‐Hodgkin Lymphoma/Treatment • Local disease (Stage Ia and IIa): local radiation • Advanced disease (Stage III and IV, any “B” symptoms): combination chemotherapy with CHOP and rituximab (antibody against CD20) C = cyclophosphamide H = adriamycin (doxorubicin or “hydroxydaunorubicin”) O = vincristine (oncovin) P = prednisone • Mucosal Associated Lymphoid Tissue − Lymphoma of stomach is associated with Helicobacter pylori − Treat with clarithromycin and amoxicillin MTB S2CK  ‐ p. 227 Hodgkin Disease  • Presentation, diagnostic tests, “B” symptoms, and staging of Hodgkin disease (HD) are same as NHL • Hodgkin disease has Reed-Sternberg cells on pathology Normal  lymphocyte MTB S2CK  ‐ p. 228 Source: commons.wikimedia.org Reed‐Sternberg  cell lymphocyte Local, Stage I, and Stage II in  80‐90% Centers around cervical area Reed‐Sternberg cells on  Differences between HD and NHL Hodgkin Disease Non‐Hodgkin Lymphoma Stage III and Stage IV in 80‐90% Disseminated No Reed‐Sternberg cellsg pathology Pathologic classification: Lymphocyte predominant has  best prognosis Lymphocyte depleted has  worst prognosis MTB S2CK  ‐ p. 228 g Pathologic classification: Burkitt and immunoblastic have worst prognosis Hodgkin Disease/Treatment   • Stage Ia and IIa: local radiation and Chemo • Stage III and IV or anyone with “B” symptoms: ABVD A = adriamycin (doxorubicin) B = bleomycin V = vinblastine Relapses after radiationV = vinblastine D = dacarbazine MTB S2CK  ‐ p. 228 Relapses after radiation therapy are treated with chemotherapy. Relapses after chemotherapy are treated with extra high dose chemotherapy and bone marrow transplantation. Hodgkin Disease/Treatment   Complications of Radiation and Chemotherapy • Radiation increases the risk of solid tumors such as breast cancer or lung cancer • Screening for breast cancer earlier after treatment • Radiation increases premature coronary diseasedisease • The risk of acute leukemia, MDS, and NHL from chemotherapy is about 1% per year MTB S2CK  ‐ p. 228 23 Which of the following is most useful to determine dosing of chemotherapy in HD? a. Echocardiogram b. Bone marrow biopsy c. Gender d MUGA or nuclear ventriculogram The other choices aren’t as accurate in determining left ventricular function d. MUGA or nuclear ventriculogram e. Hematocrit f. Symptoms MTB S2CK  ‐ p. 228‐229  Hodgkin Disease/ Adverse Effects of Chemotherapy Chemotherapeutic Agent Toxicity Doxorubicin Vincristine Cardiomyopathy Neuropathy MTB S2CK  ‐ p. 229 Bleomycin Cyclophosphamide Cisplatin Lung fibrosis Hemorrhagic cystitis Renal and ototoxicity Multiple Myeloma  • Abnormal proliferation of plasma cells • Unregulated production of useless immunoglobulin • Usually IgG or IgA • Immunoglobulins don’t fight infection, but clog up the kidney • IgM is a separate disease called Waldenström• IgM is a separate disease called Waldenström macroglobulinemia MTB S2CK  ‐ p. 229 Multiple Myeloma  • Most common presentation is... – Bone pain from pathologic fractures • Pathologic fracture: bone breaks under normal use • Due to osteoclast activating factor (OAF), which attacks the bone causing lytic lesions • OAF hypercalcemia• OAF  hypercalcemia • Infection common because abnormal plasma cells don’t make immunoglobulins effective against infection MTB S2CK  ‐ p. 229 Multiple Myeloma  • Hyperuricemia: increased turnover of nuclear material of plasma cells • Anemia: from infiltration of marrow with plasma cells • Renal failure: from immunoglobulins and Bence- Jones protein in kidney; hypercalcemia and p y; yp hyperuricemia also damage the kidney • Renal failure and infection are MCCs of death MTB S2CK  ‐ p. 229 Multiple Myeloma  • First test done is X-ray of affected bone shows lytic lesions • Serum protein electrophoresis (SPEP) shows an IgG (60%) or IgA (25%) spike of a single type or “clone.” • One clone = Monoclonal or “M” spikep • Fifteen percent have light chains or Bence-Jones protein only MTB S2CK  ‐ p. 229‐230 24 Multiple Myeloma  Additional abnormalities • Hypercalcemia • Bence-Jones protein on urine immunoelectrophoresis • Beta-2 microglobulin levels correspond to severity of disease • Smear with rouleaux• Smear with rouleaux • Elevated BUN and creatinine • Bone marrow biopsy: >10% plasma cells defines myeloma • Elevated total protein with normal albumin MTB S2CK  ‐ p. 230 Multiple Myeloma  Rouleaux • IgG paraprotein sticks to red cells causing themred cells causing them to adhere to each other in a stack or “roll” MTB S2CK  ‐ p. 230 Source: commons.wikimedia.org Multiple Myeloma  • M-spike on SPEP doesn’t mean IgM Myeloma has a decreased anion gap. MTB S2CK  ‐ p. 230 IgG is cationic. Increased cationic substances will increase chloride and bicarbonate levels. This decreases the anion gap. 69-year-old woman admitted with severe back pain that suddenly worsened--“pop” felt when she coughs and tenderness over ribs. X-ray: lytic lesions. Calcium is 2 points above normal, Hct 27%, creatinine elevated. UA: trace protein, but 24-hour urine show 5 grams of protein. What do you expect on technetium bone scan?What do you expect on technetium bone scan? a. Normal b. Lytic lesions at site of fractures c. Increased uptake diffusely d. Decreased uptake MTB S2CK  ‐ p. 230  Nuclear bone scan shows increased uptake with osteoblastic activity, which is absent in myeloma. Why the difference between the protein on urinalysis and 24-hour urine? a. False positive 24-hour urine is common in myeloma b. Calcium in urine creates false negative urinalysis c. Uric acid creates a false positive 24-hour urinec. Uric acid creates a false positive 24 hour urine d. Bence-Jones protein isn’t detected by dipstick. e. IgG in urine inactivates urine dipstick MTB S2CK  ‐ p. 230  Bence-Jones protein is detected by urine immunoelectrophoresis. Urine dipstick detects only albumin. What is the single most accurate test for myeloma? a. Skull X-rays b. Bone marrow biopsy c. 24-hour urine d. SPEP U i i l t h i  Of those with an “M-spike” of immunoglobulins, 99% don’t have myeloma. Will show lytic lesions, but not as specific Nothing besides myeloma is associated with > 10% plasma cells on bone marrow biopsy e. Urine immunoelectrophoresis (Bence-Jones protein) MTB S2CK  ‐ p. 230‐231 Most IgG spikes are from monoclonal gammopathy of unknown significance that doesn’t progress or need treatment. 25 Multiple Myeloma/Treatment  • Best initial therapy is... • Combination of steroids with lenalidomide, bortezomib, or melphalan • Most effective therapy under age 70 is autologous bone marrow transplant with stem cell support MTB S2CK  ‐ p. 231 Myeloma therapy is in a state of rapid flux due to numerous advances Monoclonal Gammopathy of  Unknown Significance  • IgG or IgA spike on SPEP is common in older patients • Evaluate with bone marrow biopsy to exclude myeloma • Monoclonal gammopathy of unknown significance (MGUS) has small numbers of plasma cells • No therapy for MGUS • 1% a year transform into myeloma • The quantity of immunoglobulin in the spike is main correlate of risk for myeloma: More MGUS = More myeloma MTB S2CK  ‐ p. 231 Waldenström Macroglobulinemia  • Overproduction of IgM • Malignant B cells lead to hyperviscosity Presents with... • Lethargy Bl i i d ti• Blurry vision and vertigo • Engorged blood vessels in eye • Mucosal bleeding • Raynaud phenomenon MTB S2CK  ‐ p. 231 Waldenström Macroglobulinemia  • Anemia common • IgM spike on SPEP results in hyperviscosity • No bone lesions • Plasmapheresis is best initial therapy • Removes IgM and  viscosity L t t t t ith hl b il• Long-term treatment with chlorambucil or fludarabine and prednisone • Control cells that make abnormal Igs • Decrease means of production MTB S2CK  ‐ p. 231 Bleeding Disorders ITP Von Willebrand Disease HemophiliaHemophilia Factor XI Deficiency DIC Thrombophilia Heparin‐Induced Thrombocytopenia • First step in evaluation is determining if bleeding is from platelets or clotting factors Bleeding Disorders  Platelet Bleeding • Superficial Factor Bleeding • Deep • Bleeding in brain or GI system can be from either platelet or clotting factor deficiency MTB S2CK  ‐ p. 232 • Epistaxis, gingival, petechiae, purpura, gums, vaginal bleeding • Joints and muscles 26 Immune (Idiopathic) Thrombocytopenic Purpura (ITP)  Look for... • Isolated thrombocytopenia – Normal Hct N l WBC t– Normal WBC count • Normal-sized spleen MTB S2CK  ‐ p. 232 23-year-old woman comes to ED with increased menstrual bleeding, gum bleeding when she brushes her teeth, and petechiae. Platelet count: 17,000/L (low) What is the next step in therapy? a. Bone marrow biopsy b. Intravenous immunoglobulins c. Prednisone d. Antiplatelet antibodies e. Platelet transfusion MTB S2CK  ‐ p. 232  Prednisone is more important than checking for increased megakaryocytes or antiplatelet antibodies, which is characteristic of ITP. ITP  • Diagnosis of exclusion Occasional tests are: • Antiplatelet antibodies lack specificity, limited benefitbenefit • Ultrasound or CT scan to exclude hypersplenism • Megakaryocytes are elevated in number MTB S2CK  ‐ p. 232 ITP/Treatment Presentation Management No bleeding, count > 30,000 Mild bleeding, count  27 Von Willebrand Disease (VWD) Diagnosis • Bleeding time: increased duration of bleeding • VWF (antigen) level may be decreased • Ristocetin cofactor assay: detects VWF dysfunction Treatment • Initial therapy: DDAVP (desmopressin), which releases subendothelial stores of VWF • If no response, use factor VIII replacement or VWF concentrate MTB S2CK  ‐ p. 233 Hemophilia Look for... • Delayed joint or muscle bleeding in male child – Bleeding delayed because primary hemostatic plug is with • Most accurate test is... – Specific assay for factor VIII or IX • Mixing studies with normal plasma correct aPTT to normal platelets • Prothrombin time (PT) normal • aPTT prolonged • Treat mild cases with DDAVP • Severe bleeding treated with replacement of specific factor MTB S2CK  ‐ p. 234 Factor XI Deficiency • Most of time, no increase in bleeding with factor XI deficiency • With trauma or surgery, there’s increased bleeding Look for... • Normal PT with prolonged aPTTp g • Mixing study: corrects aPTT to normal Treatment • Use FFP to stop bleeding MTB S2CK  ‐ p. 234 Disseminated Intravascular Coagulation (DIC) • DIC doesn’t occur in otherwise healthy people • Look for a definite risk such as... − Sepsis − Burns − Abruptio placenta or amniotic fluid embolus − Snake bitesSnake bites − Trauma resulting in tissue factor release − Cancer • There’s bleeding related to both clotting factor deficiency as well as thrombocytopenia MTB S2CK  ‐ p. 234 Disseminated Intravascular Coagulation (DIC) Diagnostic Tests • Elevated PT and aPTT • Low platelet count • Elevated D-dimer & fibrin split products • Decreased fibrinogen level (has been consumed) MTB S2CK  ‐ p. 234 Disseminated Intravascular Coagulation (DIC) Treatment • Replace platelets < 50,000/μL as well as clotting factors with FFP • Heparin has no benefit C i it t b ff ti t MTB S2CK  ‐ p. 235 • Cryoprecipitate may be effective to replace fibrinogen levels if FFP doesn’t control bleeding 28 Hypercoaguable States/Thrombophilia • MCC: –Factor V Leiden mutation • No difference in intensity of anticoagulation Warfarin to INR of 2 3 for 6 months• Warfarin to INR of 2-3 for 6 months MTB S2CK  ‐ p. 235 Heparin‐Induced Thrombocytopenia • HIT more common with unfractionated heparin – Can still occur with LMW heparin • Presents 5 to 10 days after start of heparin with a marked drop in platelet count (> 30%) • Both venous and arterial thromboses occur – Venous clots more commonVenous clots more common • HIT rarely leads to bleeding • Platelets just precipitate out Diagnostic Tests • HIT confirmed with ELISA for platelet factor 4 (PF4) antibodies or serotonin release assay MTB S2CK  ‐ p. 235 Heparin‐Induced Thrombocytopenia Treatment • Immediately stop all heparin-containing products • Can’t just switch unfractionated heparin to LMW heparin • Direct thrombin inhibitors – Argatroban lepirudin and bivalirudin– Argatroban, lepirudin, and bivalirudin • After direct thrombin inhibitor is started, use warfarin MTB S2CK  ‐ p. 235 Antiphospholipid Syndromes  Two main syndromes - lupus anticoagulant and anticardiolipin antibody • Both cause thrombosis • Anticardiolipin antibodies associated with multiple spontaneous abortions • Antiphospholipid (APL) syndromes specificallyAntiphospholipid (APL) syndromes specifically cause thrombophilia with abnormal aPTT MTB S2CK  ‐ p. 235 Antiphospholipid Syndromes  • Best initial test is... – Mixing study • Because it’s a circulating inhibitor, aPTT remains elevated after mix • Most accurate test for lupus anticoagulant is... – Russell viper venom testRussell viper venom test Treatment • Treat with heparin and warfarin as you would for any cause of DVT or PE • APL syndrome may require lifelong anticoagulation MTB S2CK  ‐ p. 235 1 Infectious Diseases Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Introduction to Antibiotics Principles of Answering Questions  Beta‐lactam Antibiotics FluoroquinolonesFluoroquinolones Aminoglycosides Doxycycline  Trimethoprim/Sulfamethoxazole  Beta‐lactam/Beta‐lactamase Combinations  Specific Organism Groups and Their Treatments Introduction to Antibiotics  • Organisms associated with diseases don’t change • But antibiotics that treat them change M t i t t thi• Most important thing • Antibiotics associated with each group of organisms MTB S2CK  ‐ p. 3 Introduction to Antibiotics  Principles of Answering Infectious Diseases Questions • The radiologic test is never “the most accurate test” • Risk factors for an infection aren’t as• Risk factors for an infection aren t as important as individual presentation • Beta-lactam antibiotics have greater efficacy than other classes MTB S2CK  ‐ p. 3 Beta‐lactam Antibiotics  Penicillins, Cephalosporins, Carbapenems, Aztreonam Penicillins • Penicillin (G, VK, benzathine) ( , , ) – Viridans group streptococci – Streptococcus pyogenes – Oral anaerobes – Syphilis – Leptospira MTB S2CK  ‐ p. 3 Penicillins  • Ampicillin and amoxicillin – Cover same organisms as penicillin And…… – E. coli – Lyme disease– Lyme disease – Gram-negative bacilli (few) MTB S2CK  ‐ p. 3 2 Penicillins  Gram-negative bacteria covered by amoxicillin H. influenzae E. coli MTB S2CK  ‐ p. 3 Listeria Proteus Salmonella Penicillins  • Answer as “Best Initial Therapy” for – Otitis media – Dental infection and endocarditis prophylaxis – Lyme disease limited to rash, joint, or 7thLyme disease limited to rash, joint, or 7 CN involvement – UTI in pregnant women – Listeria monocytogenes – Enterococcal infections MTB S2CK  ‐ p. 4 Penicillins Oxacillin, Cloxacillin, Dicloxacillin, and Nafcillin • Skin infections: Cellulitis • Endocarditis, meningitis, and bacteremia from staphylococci • Osteo & Septic arthritis only when proven sensitive • Not against Methicillin-Resistant Staphylococcus aureus (MRSA) or Enterococcus MTB S2CK  ‐ p. 4 Penicillinase‐resistant penicillins (PRPs) Methicillin is never right Causes allergic interstitial nephritis MTB S2CK  ‐ p. 4 Methicillin sensitive or resistant means oxacillin sensitive or resistant. Penicillins Piperacillin, Ticarcillin • Gram-negative bacilli (e.g., E. coli, Proteus) enterobacteriaciae & pseudomonads • “Best initial therapy” – Cholecystitis & ascending cholangitis – Pyelonephritis – Bacteremia – Hospital-acquired and ventilator-associated pneumonia – Neutropenia and fever MTB S2CK  ‐ p. 4 Piperacillin, Ticarcillin, Azlocillin, Mezlocillin • Also for: streptococci and anaerobes BUT • NOT the answer, infection exclusively from these single organisms • Use narrower agent • Combined with a beta-lactamase inhibitor such as tazobactam or clavulanic acid MTB S2CK  ‐ p. 4 3 Cephalosporins • Cross-reaction penicillin & cephalosporins is Very small (3% to 5%) • All cephalosporins, in every class, will cover group A, B, and C streptococci, viridans group streptococci, E. coli, Klebsiella, and Proteus mirabilismirabilis MTB S2CK  ‐ p. 4 Listeria, MRSA, and Enterococcus are resistant to all forms of cephalosporins. Cephalosporins If the case describes a rash to penicillin • Answer cephalosporins If the case describes anaphylaxis • You must use a non-beta-lactam antibiotic MTB S2CK  ‐ p. 5 First Generation  Cefazolin, Cephalexin, Cephradrine, Cefadroxyl 1st-gen cephalosporins treat • Staphylococci – Methicillin sensitive = oxacillin sensitive = cephalosporin sensitivecephalosporin sensitive • Streptococci (except Enterococcus) • Some gram-negative bacilli such as E. coli, but not Pseudomonas • Osteomyelitis, septic arthritis, endocarditis, cellulitis MTB S2CK  ‐ p. 5 Second Generation  Cefotetan, Cefoxitin, Cefaclor, Cefprozil, Cefuroxime, Loracarbef • Cover same organisms as 1st-gen cephalosporinscephalosporins AND • Add coverage for anaerobes & more gram-negative bacilli MTB S2CK  ‐ p. 5 Second Generation  Cefotetan, Cefoxitin, Cefaclor, Cefprozil, Cefuroxime, Loracarbef Cefotetan or cefoxitin • Best initial therapy for pelvic inflammatory disease (PID) combined with doxycycline WarningWarning • Cefotetan and cefoxitin  risk of bleeding and give a disulfiram-like reaction with alcohol Cefuroxime, loracarbef, cefprozil, cefaclor • Respiratory infections (e.g., bronchitis, otitis media, and sinusitis) MTB S2CK  ‐ p. 5 Third Generation  Ceftriaxone, Cefotaxime, Ceftazidime Ceftriaxone • First-line for pneumococcus, including partially insensitive organisms – Meningitis – Community-acquired pneumonia (in combination with macrolides) – Gonorrhea – Lyme involving heart or brain – Avoid ceftriaxone in neonates because of impaired biliary metabolism MTB S2CK  ‐ p. 5 4 Third Generation  Cefotaxime • Superior to ceftriaxone in neonates • Spontaneous bacterial peritonitis C ft idi h d lCeftazidime has pseudomonal coverage MTB S2CK  ‐ p. 5 Fourth Generation  Cefepime • Better staphylococcal coverage compared with the 3rd-generation cephalosporins –Neutropenia and fever –Ventilator-associated pneumonia–Ventilator-associated pneumonia Ceftaroline: only cephalosporin to cover MRSA MTB S2CK  ‐ p. 5 Carbapenems Imipenem, Meropenem, Ertapenem, Doripenem • Cover gram-negative bacilli, including many that’re resistant • Anaerobes • Streptococci and staphylococci • Neutropenia and fever MTB S2CK  ‐ p. 6 Ertapenem differs from other carbapenems. Ertapenem does not cover Pseudomonas Monobactams Aztreonam Only monobactam used • Exclusively –Gram-negative bacilli I l di P d–Including Pseudomonas –No cross-reaction with penicillin MTB S2CK  ‐ p. 6 Fluoroquinolones Ciprofloxacin, Gemifloxacin, Levofloxacin, Moxifloxacin • Community-acquired pneumonia, including penicillin-resistant pneumococcus • Gram-negative bacilli including most pseudomonads • Cipro: NOT for pneumococcus MTB S2CK  ‐ p. 6 Fluoroquinolones • Ciprofloxacin: Cystitis and pyelonephritis • Moxifloxacin: Not for urine/cystitis • Diverticulitis and GI infections – Combined with metronidazole – Don’t cover anaerobes except moxifloxacinDon t cover anaerobes except moxifloxacin • Moxifloxacin as single agent for diverticulitis without metronidazole MTB S2CK  ‐ p. 6 5 Fluoroquinolones Quinolones cause • Bone growth abnormalities in children and pregnant women • Tendonitis and achilles tendon rupture MTB S2CK  ‐ p. 6 Tendonitis and achilles tendon rupture • Gatifloxacin removed because of glucose abnormalities Fluoroquinolones MTB S2CK  ‐ p. 6 Source: Grook Da Oger, commons.wikimedia.org Aminoglycosides Gentamicin, Tobramycin, Amikacin • Gram-negative bacilli (bowel, urine, bacteremia) • Synergistic with beta-lactam antibioticsSynergistic with beta lactam antibiotics for enterococci and staphylococci • No effect against anaerobes (need oxygen to work) • Nephrotoxic and ototoxic MTB S2CK  ‐ p. 6 Doxycycline • Chlamydia • Lyme –Rash –Joint 7th CN–7th CN palsy • MRSA skin MTB S2CK  ‐ p. 7 Target-shaped rash of Lyme disease or erythema migrans. Source: Nishith Patel. Doxycycline • Rickettsia • Syphilis: Primary & secondary ONLY if allergic to penicillin • Borrelia, Ehrlichia, and Mycoplasma Ad ff tAdverse effects • Tooth discoloration (children) • Fanconi syndrome (Type II RTA proximal), photosensitivity • Esophagitis MTB S2CK  ‐ p. 7 Trimethoprim/Sulfamethoxazole • Cystitis • Pneumocystis pneumonia treatment and prophylaxis • MRSA of skin and soft tissue (cellulitis) • Rash • Hemolysis (G6PD deficiency) • Marrow suppression (folate antagonist) MTB S2CK  ‐ p. 7 Nitrofurantoin has one indication: Cystitis, especially in pregnant women. 6 Beta‐lactam/Beta‐lactamase Combinations  • Amoxicillin/clavulanate • Ticarcillin/clavulanate • Ampicillin/sulbactam • Piperacillin/tazobactam Beta lactamase adds staphylococci effect• Beta-lactamase adds staphylococci effect • Sensitive Staph only MTB S2CK  ‐ p. 7 Gram‐Positive Cocci: Staphylococci and  Streptococci  Best initial therapy: • Oxacillin, cloxacillin, dicloxacillin, nafcillin • First-generation cephalosporins: Cefazolin, cephalexin • Fluoroquinolones• Fluoroquinolones • Macrolides (azithromycin, clarithromycin, erythromycin) are third-line – Less efficacy than oxacillin or cephalosporins – Erythromycin more toxic MTB S2CK  ‐ p. 7 Oxacillin (Methicillin)‐Resistant Staph  • Vancomycin • Linezolid: Reversible bone marrow toxicity • Daptomycin • Tigecycline • CeftarolineCeftaroline MTB S2CK  ‐ p. 7 Minor MRSA infections of skin are treated with: TMP/SMX Clindamycin Doxycycline Anaerobes • Oral (above diaphragm) – Penicillin (G, VK, ampicillin, amoxicillin) – Clindamycin – Metronidazole (GI) MTB S2CK  ‐ p. 8 Piperacillin, carbapenems, and 2nd-generation cephalosporins also cover anaerobes Gram‐Negative Bacilli (E. coli, Klebsiella,  Proteus, Pseudomonas, Enterobacter, Citrobacter)  • Bowel (peritonitis, diverticulitis) • Urinary tract (pyelonephritis) • Cholecystitis or Cholangitis – Quinolones – Aminoglycosides – Carbapenems – Piperacillin, ticarcillin – Aztreonam – Cephalosporins MTB S2CK  ‐ p. 8 Man admitted with E. coli bacteremia. Which of the following is the most appropriate therapy? a. Vancomycin b. Linezolid c. Quinolones, aminoglycosides, carbapenems, MTB S2CK  ‐ p. 8 c. Quinolones, aminoglycosides, carbapenems, piperacillin, ticarcillin, or aztreonam d. Doxycycline e. Clindamycin f. Oxacillin  They don’t cover gram- negative bacilli. 7 Central Nervous System Infections Meningitisg Encephalitis  Central Nervous System  (CNS) Infections All CNS infections give • Fever • Headache • Vomiting • Seizures MTB S2CK  ‐ p. 9 Clues to Answering the  “Most Likely Diagnosis” Question Symptom Diagnosis Stiff neck Photophobia Meningismus Meningitis MTB S2CK  ‐ p.  Confusion Focal neurological  findings Encephalitis Abscess Meningitis/Definition • Infection/inflammation of CNS covering Source: SVG by Mysid, original by SEER Development Team commons.wikimedia.org Meningitis/Etiology: 4 bugs 95% of cases Streptococcus pneumonia (60%) Group B streptococci (14%) Haemophilus influenzae (7%) Neisseria meningitidis (15%) Listeria (2%) Staphylococcus with recent neurosurgery MTB S2CK  ‐ p. 9 S. Pneumoniae Source: CDC/Dr. M.S. Mitchell Meningitis/Presentation • Fever • Headache • Neck stiffness (nuchal rigidity) • Photophobia• Photophobia MTB S2CK  ‐ p. 9 Patient with Neck stiffness. Source: Sophian, Abraham: Epidemic cerebrospinal meningitis (1913), St. Louis, C.V Mosby , commons.wikimedia.org 8 Meningitis/Presentation • Acute bacterial (presents in several hours) • Focal abnormalities: 30% • If confusion occurs, you won’t be able to answer “What is the most likely diagnosis?” without a CT and lumbar puncture (LP) • Cryptococcal meningitis: Slow several weeks MTB S2CK  ‐ p. 9 “What is the Most Likely Diagnosis?” AIDS with 9 Meningitis/Diagnostic Tests  If there’s a contraindication to immediate LP, giving antibiotics is best initial step in management B tt t t t d MTB S2CK  ‐ p. 10 Better to treat and decrease the accuracy of a test than to risk permanent brain damage. Bacterial Antigen Detection  (Latex Agglutination Tests)  • Similar accuracy to Gram stain • If positive, they’re extremely specific • If negative, could still have infection • Not sufficiently sensitive to exclude bacterial i itimeningitis When is a bacterial antigen test indicated? • Those receiving antibiotics prior to LP • Culture may be falsely negative MTB S2CK  ‐ p. 11 “What is the Most Accurate Diagnostic Test?” Tuberculosis • Acid fast stain and culture Lyme and Rickettsia Specific serologic testing, ELISA, western blot, PCR Cryptococcus Viral Diagnosis of exclusion MTB S2CK  ‐ p. 11 Acid fast stain and culture on 3 high-volume lumbar punctures • Centrifuge to concentrate the organisms • TB has high CSF protein • Uncentrifuged sample of CSF: 10% sensitivity India ink is 60% to 70% sensitive Cryptococcal antigen: > 95% sensitive and specific Meningitis/Treatment • Bacterial: Ceftriaxone, Vancomycin, and Steroids • Base treatment answer on cell count Culture • Needs 2 to 3 days • Never available when treatment decision is made G t iGram stain • Good if positive • False negative: 30% to 50% Protein & Glucose • Nonspecific • Doesn’t allow treatment decision MTB S2CK  ‐ p. 11 Meningitis/Treatment Steroids (dexamethasone) • Lowers mortality only in S. pneumoniae • Give when thousands of neutrophils present • No culture results for several days Thousands of neutrophils on MTB S2CK  ‐ p. 11 Thousands of neutrophils on CSF = ceftriaxone, vancomycin, and steroids. Add ampicillin if immunocompromised for Listeria. Listeria Monocytogenes  • Resistant to cephalosporins • Sensitive to penicillins • Add Ampicillin to Ceftriaxone and Vancomycin if case describes risk factors for Listeria. • Risks – Elderly– Elderly – Neonates – Steroid use – AIDS or HIV – Immunocompromised (includes alcoholism) – Pregnant MTB S2CK  ‐ p. 11 10 Neisseria meningitidis  Respiratory isolation • Rifampin or Ciprofloxacin to close contacts “Close contacts” • Major respiratory fluid contact • Household contacts• Household contacts • Kissing • Sharing cigarettes or eating utensils MTB S2CK  ‐ p. 12 Neisseria meningitidis  • Routine school and work contacts are not close contacts • Healthcare workers qualify only if they –Intubate patient Perform suctioning–Perform suctioning Or –Have contact with respiratory secretions MTB S2CK  ‐ p. 12 Man comes to emergency department with fever, severe headache, neck stiffness, and photophobia. He has weakness in his left arm and leg. What’s the next step in management? a. Ceftriaxone, Vancomycin, and Steroids  b. Head CT c. Ceftriaxone d. Neurology consultation e. Steroids MTB S2CK  ‐ p. 12 Focal neurological deficits, initiate therapy Not sufficient Almost always wrong Meningitis Consultation is almost always a wrong answer on USMLE Step 2 CK What is the most common l i l d fi it f MTB S2CK  ‐ p. 12 neurological deficit of untreated bacterial meningitis? Eighth cranial nerve deficit or deafness. Encephalitis • Acute onset – Fever, and – Confusion • Many causes – Herpes simplex (most common)( ) • Must do head CT first because of confusion MTB S2CK  ‐ p. 12 What is the most accurate test of herpes encephalitis? a.Brain biopsy b.PCR of CSF c MRI  Less accurate than PCR The radiologic test is never “the most acc rate test”c.MRI d.Viral culture of CSF e.Tzanck prep f. Serology for herpes (IgG, IgM) MTB S2CK  ‐ p. 13 Useless, 95% population positive Best initial test for genital lesion Most accurate test for genital, skin lesions “the most accurate test” 11 Encephalitis/Treatment Acyclovir • “Best initial therapy” (Herpes encephalitis) Famciclovir & Valacyclovir IV unavailable• IV unavailable Foscarnet • Acyclovir-resistant herpes MTB S2CK  ‐ p. 13 A woman with herpes encephalitis confirmed by PCR gets 4 days of acyclovir. Her creatinine level rises. What’s the most appropriate next step in management? a. Stop acyclovir a Reduce the dose of acyclovir and hydrate Important to treat a. Reduce the dose of acyclovir and hydrate b. Switch to oral famciclovir or valacyclovir c. Switch to foscarnet MTB S2CK  ‐ p. 13 Insufficient for herpes encephalitis  > Nephrotoxicity than acyclovir Head and Neck Infections Otitis Media Sinusitis Pharyngitis Influenza (The “Flu”)  Otitis Media • Redness • Immobility • Bulging • Decreased light reflex • Pain • Decreased hearing • Fever MTB S2CK  ‐ p. 13 Otitis media. Source: www.sharinginhealth.ca Which of the following is the most sensitive physical finding for otitis media? a. Redness b. Immobility c. Bulging d. Decreased light reflex e. Decreased hearing MTB S2CK  ‐ p. 13‐14 They’re less sensitive Otitis Media/Diagnostic Tests/Treatment  Tympanocentesis: • Sample of fluid for culture • “Most accurate diagnostic test” Choose tympanocentesis if: • Multiple recurrences • No response to multiple antibiotics Radiologic tests for otitis are always the wrong answer MTB S2CK  ‐ p. 14 12 Otitis Media/Treatment • Amoxicillin: “Best initial therapy” • If no response to amoxicillin or it recurs, answer: • Amoxicillin/clavulanate A ith i l ith i• Azithromycin or clarithromycin • Cefuroxime or loracarbef • Levofloxacin, gemifloxacin, moxifloxacin MTB S2CK  ‐ p. 14 Quinolones are relatively contraindicated in children 34-year-old woman with facial pain, discolored nasal discharge, bad taste in mouth, fever and facial tenderness. Which of the following is the most accurate diagnostic test? a Sinus biopsy or aspiratea.Sinus biopsy or aspirate b.CT scan c.X-ray d.Culture of the discharge e.Transillumination MTB S2CK  ‐ p. 14  Radiologic test never “the most accurate test” Always the wrong answer for sinusitis Doesn’t provide precise microbiological diagnosis Sinusitis Use Sinus Biopsy or Aspirate Culture of nasal discharge is always the wrong answer for sinusitis Use Sinus Biopsy or Aspirate • Infection frequently recurs • No response to different empiric therapies MTB S2CK  ‐ p. 14 34-year-old woman with facial pain, discolored nasal discharge, bad taste in her mouth, and fever. She has facial tenderness. What is the most appropriate next step, action, or management? a Linezolid Excellent for resistant gram-positive, a. Linezolid b. CT scan c. X-ray d. Amoxicillin and decongestant e. Erythromycin and decongestant MTB S2CK  ‐ p. 15 Diagnosis is clear, radiologic testing unnecessary Poor coverage for S. pneumoniae g p doesn’t cover Haemophilus  Pharyngitis • Pain on swallowing • Enlarged lymph nodes in neck • Exudate in pharynx • Fever • No cough and no hoarseness• No cough and no hoarseness • These features make the likelihood of streptococcal pharyngitis exceed 90% MTB S2CK  ‐ p. 15 Streptococcal pharyngitis. Source: James Heilman, MD Pharyngitis/Diagnostic Tests  “Best initial test”: “Rapid strep test” • An office/clinic-based test • Finds group A beta-hemolytic streptococci in minutes • Negative test excludes disease and no antibiotics are neededare needed • Positive rapid strep test = positive pharyngeal culture • Small vesicles or ulcers: HSV or herpangina • Membranous exudates: Diphtheria, Vincent angina, or EBV MTB S2CK  ‐ p. 15 13 Pharyngitis/Treatment  1. Penicillin or amoxicillin is best initial therapy 2. Penicillin allergic: – Cephalexin (reaction only rash) – Clindamycin or macrolide (anaphylaxis) MTB S2CK  ‐ p. 15 Streptococcal pharyngitis treated to prevent rheumatic fever Influenza (The “Flu”)  • Arthralgias/myalgias • Cough • Fever • Headache • Sore throatSore throat • Nausea, vomiting, or diarrhea, especially in children MTB S2CK  ‐ p. 16 Source: Mikael Häggström Influenza (The “Flu”)  • The “most appropriate next step in management” depends on time course from presentation Within 48 hours of onset • Perform nasopharyngeal swab or washPerform nasopharyngeal swab or wash • Rapidly detects antigen associated with influenza MTB S2CK  ‐ p. 16 Influenza (The “Flu”)/Treatment  < 48 hours of symptoms: • Oseltamivir, zanamivir • Neuraminidase inhibitors shorten duration of symptoms • Treats both influenza A and B > 48 hours of symptoms:> 48 hours of symptoms: Symptomatic treatment only • Analgesics, rest, antipyretics, hydration MTB S2CK  ‐ p. 16 Oseltamivir and zanamivir don’t successfully treat complications of influenza such as pneumonia. Infectious Diarrhea Blood and WBCs in Stool  No Blood or WBCs in Stool  Blood and WBCs in Stool  When you see...in the history the answer is…. Poultry • Salmonella • Campylobacter: MCC associated with• Campylobacter: MCC associated with Guillain-Barre Syndrome • E. coli 0157:H7—Hemolytic Uremic Syndrome (HUS) • Shigella: 2nd most common association with HUS MTB S2CK  ‐ p. 16 14 Blood and WBCs in Stool  Shellfish and cruise ships • Vibrio parahaemolyticus: Shellfish, liver & skin disease • Vibrio vulnificus: Hemochromatosis blood transfusionsHemochromatosis, blood transfusions • Yersinia: High affinity for iron Antibiotics, white and red cells in stool • Clostridium difficile MTB S2CK  ‐ p. 16 Blood and WBCs in Stool  • The “Best initial test” is: Blood and/or fecal leukocytes • Won’t determine specific organism • Stool lactoferrin: Greater iti it & ifi itsensitivity & specificity than stool leukocytes • Lactoferrin: Better answer than fecal leukocytes if one of the choices • Most accurate test is stool culture MTB S2CK  ‐ p. 16 WBC’s in a stool sample (Methylene Blue Stain). Source: Bobjgalindo No Blood NoWBCs in Stool  • Viral • Giardia: – Camping/hiking and unfiltered fresh water • Cryptosporidiosis: – AIDS 15 Acute Hepatitis/Definition/Etiology • Infection or inflammation of liver • Majority of acute cases are viral hepatitis A/B Hepatitis C • Rarely presents with acute infection • Found on blood tests for liver functionFound on blood tests for liver function • Evaluation of cirrhosis Hepatitis D • Exclusively as coinfection of hepatitis B • IDUs MTB S2CK  ‐ p. 17 Acute Hepatitis Hepatitis E Worst in pregnancy East Asia S Bl d M H titi B C D MTB S2CK  ‐ p. 18 Sex, Blood, Mom: Hepatitis B, C, D Food and water (enteric): Hepatitis A and E • You Ate hepatitis A & you Eat hepatitis E Acute Hepatitis/Presentation • No way to detect specific type from symptoms All forms present with: • Jaundice F i ht l d f ti• Fever, weight loss, and fatigue • Dark urine • Hepatosplenomegaly • Nausea, vomiting, abdominal pain MTB S2CK  ‐ p. 18 Acute Hepatitis/Diagnostic Tests • Increased direct bilirubin • Increased ratio of alanine aminotransferase (ALT) to aspartate aminotransferase (AST) • Increased alkaline phosphatase MTB S2CK  ‐ p. 18 Aplastic anemia is a rare complication of acute hepatitis Which correlates with increased mortality? a. Bilirubin b. Prothrombin time c. ALT d AST  All can be markedly elevated and better fast, d. AST e. Alkaline phosphatase except PT MTB S2CK  ‐ p. 18 Disease‐Specific Diagnostic Tests  Hepatitis A, C, D, and E: “Best initial diagnostic test” • IgM antibody: Acute infection • IgG antibody: Resolution of infection Hepatitis C: Disease activity • PCR RNA level = Amount of active viral replication • Hepatitis C PCR level = First thing to change • PCR drop = Improvement with treatment • PCR rises = Treatment failure MTB S2CK  ‐ p. 18 16 Serologic Patterns Acute or chronic  infection Resolved, old, past  infection Surface  antigen e‐antigen Positive Positive Negative Negative MTB S2CK  ‐ p. 19 Core antibody Surface  antibody  Positive IgM or IgG Negative Positive IgG Positive Serologic Patterns Vaccination “Window period” Surface  antigen e‐antigen Negative Negative Negative Negative MTB S2CK  ‐ p. 19 Core antibody Surface  antibody  Negative Positive Positive IgM, then  IgG Negative  Which becomes abnormal first after acquiring hepatitis B infection? a. Bilirubin b. e-antigen Viral replication rises after S Ag c. Surface antigen d. Core IgM antibody e. ALT f. Anti-hepatitis B e-antibody MTB S2CK  ‐ p. 19  Measure of body’s response to infection Resolution starting Which of the following is the most direct correlate with the amount/quantity of active viral replication? a. Bilirubin b. e-antigen c. Surface antigen  Doesn’t tell quantity d. Core IgM antibody e. ALT f. Anti-hepatitis B e-antibody MTB S2CK  ‐ p. 19 Measure of body’s response to infection Will appear prior to resolution of all DNA polymerase activity Which indicates you can’t transmit infection (i.e., active infection has resolved)? a. Bilirubin normalizes b No e-antigen found Normalize long before viral replication stops. No viral replicationb. No e antigen found c. No surface antigen found d. No core IgM antibody found e. ALT normalizes f. Anti-hepatitis B e-antibody MTB S2CK  ‐ p. 19‐20  Will appear prior to resolution of all DNA polymerase activity No viral replication No serological evidence of disease Which is the best indication of the need for treatment in chronic disease? a. Bilirubin b. e-antigen At least some active disease, it might be on the way to c. Surface antigen d. Core IgM antibody e. ALT f. Anti-hepatitis B e-antibody MTB S2CK  ‐ p. 20 it might be on the way to spontaneous resolution and wouldn’t benefit Measure of body’s response to infection 17 Which of the following is the best indicator that a pregnant woman will transmit infection to her child? a. Bilirubin b. e-antigen c. Surface antigen  At least some active disease, it might be on the way to spontaneous resolution and wouldn’t benefit. Perinatal transmission: 10% if d. Core IgM antibody e. ALT f. Anti-hepatitis B, e-antibody MTB S2CK  ‐ p. 20 Measure of the body’s response to infection positive surface antigen, but e- antigen is negative; 90% when both positive Acute hepatitis/Treatment Hepatitis A and E: • Resolve spontaneously over weeks • Almost always benign conditions Hepatitis B: Ch i i 10% Only acute hepatitis C gets medical therapy Chronic in 10% No treatment for acute disease Hepatitis C: • Use interferon, ribavirin and either telaprevir or boceprevir!!! • Treatment decreases likelihood of chronic infection MTB S2CK  ‐ p. 21 Chronic Hepatitis/Treatment Chronic hepatitis B = Surface antigen > 6 months e-antigen = Elevated level of DNA polymerase Treat when BOTH surface and e-antigen are positive Entecavir, or Adefovir, or T f iTenofovir, or Lamivudine, or Telbivudine, or Interferon (joint & muscle pain, depression, the “flu”) • Interferon is an injection • Interferon has most adverse effects MTB S2CK  ‐ p. 21 Chronic Hepatitis/Treatment Adverse effects of interferon: • Arthralgia/myalgia • Leukopenia & thrombocytopenia • Depression & flu-like symptoms MTB S2CK  ‐ p. 21 Goal of hepatitis therapy: • Reduce DNA polymerase • Convert e-antigen to anti-hepatitis e-antibody Role of Liver Biopsy  • Fibrosis is a strong indication to begin therapy for either hepatitis B or C right away • Fibrosis + Active Viral replication will progress to cirrhosis • Cirrhosis: Irreversible Who will progress? • Old terms “chronic active” or “chronic persistent” hepatitis are unhelpful • DNA polymerase level is helpful MTB S2CK  ‐ p. 21 Chronic Hepatitis ALT levels aren’t a good indication of chronic hepatitis activity. You can have significant infection MTB S2CK  ‐ p. 21 have significant infection with normal transaminase levels. 18 Treatment of Chronic Hepatitis C  • There’s no way to determine the duration of infection with hepatitis C, since there’s no equivalent of surface antigen test • Most patients don’t have acute symptoms • If PCR-RNA viral load is elevated, patientsIf PCR RNA viral load is elevated, patients should be treated with interferon and ribavirin and either boceprevir or telaprevir MTB S2CK  ‐ p. 21 Treatment of Chronic Hepatitis C  • Three Drugs! • 80% resolution with 3 drugs • Interferon AND Ribavirin AND either • Telaprevir OR Boceprevir MTB S2CK  ‐ p. 21‐22 Ribavirin causes anemia Sexually Transmitted Diseases Urethritis Cervicitis Pelvic Inflammatory Disease (PID) Syphilis Genital Warts (Condylomata Acuminata) Pediculosis (Crabs) Scabies  Urethritis • Look for urethral discharge to answer “What is the most likely diagnosis?” Both urethritis & cystitis give: • Dysuria • Frequency• Frequency • Burning Cystitis: No discharge MTB S2CK  ‐ p. 22 Urethritis/Diagnostic Tests  “Best initial test” Men: Urethral swab for Gram stain & WBCs • Intracellular gram-negative diplococci = Neisseria gonorrhoeae • Urine for nucleic acid amplification test (NAAT) detects gonorrhea and Chlamydia • NAAT or DNA probe: “Most accurate test” Other causes of urethritis: Mycoplasma genitalium Ureaplasma Women: Self-administered vaginal swab MTB S2CK  ‐ p. 22 Urethritis/Treatment Gonorrhea Chlamydia Combine: One drug for gonorrhea & one for Chlamydia • Quinolones aren’t the best initial therapy because of resistance MTB S2CK  ‐ p. 22 Gonorrhea Chlamydia Cefixime Ceftriaxone Azithromycin Doxycycline 19 Cervicitis • Cervical discharge • Inflamed “strawberry” cervix • Testing & treatment are identical to previous description for urethritis E t lf d i i t d i l b• Except self-administered vaginal swab for NAAT MTB S2CK  ‐ p. 22 PID/Presentation • Lower abdominal tenderness • Lower abdominal pain • Fever • Cervical motion tenderness • LeukocytosisLeukocytosis Always to exclude pregnancy first!! MTB S2CK  ‐ p. 22‐23 PID/Diagnostic Tests  Cervical swab for: • Culture • DNA probe or nucleic acid amplification (NAAT) • Tests clarify need for treating partnery g p • Culture preferred to determine resistance MTB S2CK  ‐ p. 23 Cervical testing isn’t the “most accurate test” for PID. Laparoscopy in PID  • The most accurate test for PID • Only rarely needed Laparoscopy is answer if: • Diagnosis is unclear Symptoms persist despite therapy• Symptoms persist despite therapy • Recurrent episodes for unclear reasons MTB S2CK  ‐ p. 23 PID/Treatment  • Combination of medications for gonorrhea and Chlamydia • Inpatient: Cefoxitin or cefotetan combined with doxycycline • Outpatient: Ceftriaxone and doxycycline (possibly with metronidazole) Anaphylaxis to penicillin?: • Levofloxacin and metronidazole (outpatient) • Clindamycin and gentamicin (inpatient) MTB S2CK  ‐ p. 23 Ulcerative Genital Disease/  “What Is the Most Likely Diagnosis?” Often impossible to determine specific diagnostic, visual characteristics Question must have sufficient evidence to give answer • All genital ulcers can have inguinal adenopathy MTB S2CK  ‐ p. 23 g 20 Presentation of STDs History and physical findings Most likely diagnosis Painless ulcer  Painful ulcer  Syphilis Chancroid (Haemophilus ducreyi) MTB S2CK  ‐ p. 23 Lymph nodes tender and  suppurating  Vesicles prior to ulcer  and painful Lymphogranuloma venereum Herpes simplex Diagnostic Tests  Diagnosis Diagnostic Test Syphilis Chancroid (Haemophilus  ducreyi) Dark‐field microscopy (Best in primary) VDRL or RPR (75% sensitive in primary) FTA or MHA‐TP (confirmatory) Stain & culture (special media)  MTB S2CK  ‐ p. 24 ducreyi)  Lymphogranuloma  venereum  Herpes simplex  Complement fixation titers in blood  Nucleic acid amplification testing on  swab Tzanck prep: “Best initial test” Viral culture: “Most accurate test” Diagnostic Tests  If dark-field is positive for spirochetes no further testing for syphilis is necessary MTB S2CK  ‐ p. 24 necessary. Treatment Diagnosis Treatment Syphilis  Chancroid (Haemophilus ducreyi) One dose IM benzathine penicillin  Doxycycline, if penicillin allergic Azithromycin (single dose) MTB S2CK  ‐ p. 24 Lymphogranuloma venereum Herpes simplex Doxycycline Acyclovir, valacyclovir, famciclovir Foscarnet for acyclovir‐resistant  herpes Woman comes to clinic with multiple painful genital vesicles. What is the next step in management? a. Acyclovir orally b. Acyclovir topically  Worthlessy p y c. Tzanck prep d. Viral culture e. Serology f. PCR MTB S2CK  ‐ p. 24 Can’t distinguish genital infection from oral infection in the past Most accurate test, but not necessary, if vesicles are clear If the presentation is diagnostic testing is not necessary PCR encephalitis, not genital Syphilis/Presentation Primary Syphilis • Painless genital ulcer with heaped-up indurated edges (it becomes painful if it becomes secondarily infected with bacteria) • Painless adenopathy MTB S2CK  ‐ p. 25 © Richard Usatine, M.D. Used with permission Chancres heal spontaneously even without treatment. Penicillin prevents later stages. 21 Syphilis/Presentation Secondary Syphilis • Rash (palms and soles) • Alopecia areata • Mucous patches• Mucous patches • Condylomata lata MTB S2CK  ‐ p. 25 phil.cdc.gov Syphilis/Presentation Tertiary Syphilis • Neurosyphilis – Meningovascular (stroke from vasculitis) – Tabes dorsalis (loss of position and vibratory sense, incontinence, cranial nerve) MTB S2CK  ‐ p. 25 Tabes Dorsalis . Source: CDC/Susan Lindsley Syphilis/Presentation Tertiary Syphilis • Neurosyphilis – General paresis (memory and personality changes) – Argyll Robertson pupilArgyll Robertson pupil • Aortitis (aortic regurgitation, aortic aneurysm) • Gummas (skin and bone lesions) MTB S2CK  ‐ p. 25 Sensitivity of Diagnostic Tests by Stage  Test VDRL or RPR FTA‐ABS Primary  Secondary 75%–85% 99%  95%  100% MTB S2CK  ‐ p. 25 Tertiary 95% 98% Syphilis False positive VDRL/RPR • Infection, older age, injection drug use, AIDS, malaria, antiphospholipid syndrome, and endocarditis MTB S2CK  ‐ p. 25 Titers of VDRL or RPR are reliable at > 1:8 Lower titer is more often falsely positive High titers (> 1:32) are rarely false positive Syphilis/Treatment  Primary & secondary syphilis: • Single IM injection of penicillin • Oral doxycycline: Penicillin allergy Tertiary syphilis: IV penicillin• IV penicillin • Desensitize to penicillin if allergic MTB S2CK  ‐ p. 25 22 Syphilis Jarisch-Herxheimer reaction • Fever, headache, myalgias after treatment • Give aspirin & antipyretics (it’ll pass) MTB S2CK  ‐ p. 26 Desensitization the answer for neurosyphilis and pregnant women Genital Warts (Condylomata Acuminata)/ Diagnosis • Papillomavirus • Diagnose based on the visual appearance WWrong answers: • Biopsy • Serology • Stain, smear, or culture MTB S2CK  ‐ p. 26 Condylomata acuminata (genital warts). Source: Farshad Bagheri, MD. Genital Warts (Condylomata Acuminata)/ Treatment Remove by physical means: • Cryotherapy with liquid nitrogen • Surgery for large ones • Laser • “Melt” with podophyllin or trichloroacetic acid • Imiquimod: Apply locally (immunostimulant leads to sloughing off of lesion) MTB S2CK  ‐ p. 26 Pediculosis (Crabs)  • Hair-bearing areas (axilla, pubis) • Itchy • Visible on surface • Treat with permethrin; li d i l ilindane is equal in efficacy, but more toxic MTB S2CK  ‐ p. 26 Pediculosis pubis. Source: commons.wikimedia. Used with permission Scabies  • Web spaces between fingers and toes or at elbows • Around nipples near the genitals • Burrows visible (theyBurrows visible (they dig) but smaller than pediculosis • Scrape & magnify MTB S2CK  ‐ p. 27 Scabies burrow under the skin and must be scraped out to establish a diagnosis. Source: Conrad Fischer, MD. Scabies/Treatment • Permethrin • Widespread disease: Oral Ivermectin • Severe disease needs repeat dosing MTB S2CK  ‐ p. 27 23 Urinary Tract Infections Cystitis Pyelonephritisy p Acute Prostatitis Perinephric Abscess Urinary Tract Infections (UTI)  • Present with dysuria (frequency, urgency, burning), maybe fever • Urinalysis shows  WBCs • E. coli “MCC” • Quinolones “Best initial therapy” • Anatomic defects lead to UTIs: – Stones – Strictures – Tumor or prostate hypertrophy – Diabetes MTB S2CK  ‐ p. 27 Urinary Tract Infections  • Foley catheter is a foreign body • Neurogenic bladder is an obstruction Frequency = Multiple episodes of micturation MTB S2CK  ‐ p. 27 Polyuria = Increase in volume of urine Cystitis Presents with dysuria and: • Suprapubic pain/discomfort • Mild/absent fever Men have anatomic abnormalities MTB S2CK  ‐ p. 27‐28 Women most often don’t Best initial test: Urinalysis with > 10 WBCs Most accurate test: Urine culture Cystitis/Treatment • Trimethoprim/sulfamethoxazole (TMP/SMZ) if local resistance is low • Ciprofloxacin • Cephalexin • Nitrofurantoin (Pregnant women) ( g ) MTB S2CK  ‐ p. 28 All beta-lactam antibiotics are considered safe in pregnancy 36 year old generally healthy woman comes with urinary frequency and burning. UA: > 50 WBC What is the next step in management? a. TMP/SMZ for 3 days b. TMP/SMZ for 7 days c. Urine culture d. Ultrasound of urinary system e. CT scan of urinary system MTB S2CK  ‐ p. 28  With anatomic abnormality No need of culture or imaging when symptoms of cystitis are clear & WBCs in urine 24 Pyelonephritis Dysuria with: • Flank or CVA tenderness • High fever • Occasional abdominal pain • UA with high WBCs • Imaging studies (CT or sonogram) look for anatomic abnormalities causing infection MTB S2CK  ‐ p. 28 Pyelonephritis Treat with: • Ampicillin & gentamicin • Ciprofloxacin • Change based on culture/sensitivity MTB S2CK  ‐ p. 28 Any drugs for gram-negative bacilli would be effective for pyelonephritis Acute Prostatitis Dysuria with: • Perineal pain • Tender prostate on examination • Diagnostic yield of urine culture greatly increased with prostate massage p g • Treat same as you would for pyelonephritis • Longer duration • TMP/SMZ or ciprofloxacin for 6 to 8 weeks for chronic prostatitis MTB S2CK  ‐ p. 29 Perinephric Abscess Look for: • Pyelonephritis not resolving with appropriate therapy • When drug choice & dose are correct failure of infection to resolve is an anatomic problem • Do sonogram or CT scan • Drainage of fluid collection is mandatory • Culture of infected fluid is essential to guide therapy MTB S2CK  ‐ p. 29 Endocarditis Endocarditis/Definition • Heart valve infection • Leads to fever & murmur Diagnosis: • Positive blood cultures Vegetations on echocardiogram• Vegetations on echocardiogram MTB S2CK  ‐ p. 29 25 Endocarditis/Etiology • Rare on normal heart valves (except IDUs) • Risk proportional to degree of damage of valves • Regurgitant & stenotic lesions have• Regurgitant & stenotic lesions have increased risk • Prosthetic valves: Highest risk MTB S2CK  ‐ p. 29 Endocarditis/Etiology Can develop on normal valves if: • Severe bacteremia • Highly pathogenic organisms (Staphylococcus aureus) • Dental procedures with blood confer a small risk of endocarditisrisk of endocarditis • Surgery of mouth & respiratory tract confers no risk unless severe valve disease is present • Artificial valve or cyanotic heart disease • Endoscopy confers no risk even with biopsy MTB S2CK  ‐ p. 29 Endocarditis/ What Is the Most Likely Diagnosis?” • Fever • New murmur or change in a murmur • Complications of endocarditisendocarditis – Splinter hemorrhages – Janeway lesions (flat and painless) MTB S2CK  ‐ p. 29‐30 Source: Splarka http://en.wikipedia.org/wiki/Splinter_hemorrhages Endocarditis/Presentation/ “What Is the Most Likely Diagnosis?” – Osler nodes (raised and painful) – Roth spots in eyes – Brain (mycotic aneurysm) – Kidney (hematuria, glomerulonephritis) – Conjunctival petechiae – Splenomegaly – Septic emboli to lungs MTB S2CK  ‐ p. 30 Endocarditis/Diagnostic Tests  “Best initial test” Blood culture (95%–99% sensitive) • If positive do an Echo • Transthoracic echo (60% sensitive, but 95% specific) T h l h (95% iti d• Transesophageal echo (95% sensitive and specific) • EKG rarely shows atrioventricular (AV) block if dissection of conduction system occurs (5%– 10%) MTB S2CK  ‐ p. 30 Fever + murmur = endocarditis A man comes into the ED with fever and a murmur. Blood cultures grow Streptococcus bovis. Transthoracic echocardiography shows vegetation. What is the next step in the management? a. Colonoscopy b Transesophageal echocardiogram  Transthoracic showed vegetation. b. Transesophageal echocardiogram c. CT of the abdomen d. Repeat the blood cultures e. Surgical valve replacement MTB S2CK  ‐ p. 30‐31 Will not show diverticuli No point, already positive Premature 26 How to Diagnose  Culture Negative Endocarditis 1. Oscillating vegetation on echocardiography 2. Three minor criteria: – Fever – Risk: IDU or prosthetic valve – Embolic phenomena MTB S2CK  ‐ p. 31 Endocarditis/Treatment  Empiric: • Vancomycin and gentamicin When culture results are available • Treat based on sensitivities MTB S2CK  ‐ p. 31 Endocarditis/Treatment Organism Treatment Viridans streptococci  Staphylococcus aureus (sensitive)  Ceftriaxone for 4 weeks Oxacillin, nafcillin, or  cefazolin MTB S2CK  ‐ p. 31 Fungal  Amphotericin and valve  replacement Endocarditis/Treatment Organism Treatment Staphylococcus  epidermidis or resistant  Staphylococcus  Vancomycin MTB S2CK  ‐ p. 31 Enterococci Ampicillin & gentamicin Endocarditis Treatment of Resistant Organisms • Add aminoglycoside & extend duration of treatment When Is Surgery the Answer? • CHF or ruptured valve or chordae tendineae • Prosthetic valves • Fungal endocarditis • Abscess • AV block • Recurrent emboli while on antibiotics MTB S2CK  ‐ p. 31 Endocarditis Add rifampin for prosthetic valve endocarditis with Staphylococcus. MTB S2CK  ‐ p. 31‐32 The single strongest indication for surgery is acute valve rupture and CHF. 27 Treatment of Culture Negative Endocarditis  • Most common culture negative = Coxiella • HACEK: Acronym for organisms difficult to culture causing endocarditis – Haemophilus aphrophilus – Haemophilus parainfluenza – Actinobacillus – Cardiobacterium – Eikenella – Kingella • Use ceftriaxone for HACEK group MTB S2CK  ‐ p. 32 Prophylaxis for Endocarditis  • Use prophylaxis if there’s BOTH: 1. Significant cardiac defect – Prosthetic valve – Previous endocarditis – Cardiac transplant recipient with valvulopathy – Unrepaired cyanotic heart disease AND! 2. Risk of bacteremia – Dental work with blood – Respiratory tract surgery that produces bacteremia MTB S2CK  ‐ p. 32 Prophylaxis for Endocarditis  • Amoxicillin prior to procedure • If penicillin allergic use clindamycin, azithromycin, or clarithromycin Procedures and anatomic abnormalities that do not need prophylaxis are:that do not need prophylaxis are: • Flexible endoscopy, even with biopsy, ERCP • Obstetrical and gynecologic procedures MTB S2CK  ‐ p. 32 Prophylaxis for Endocarditis  • Urology procedures (including prostate biopsy) • Mitral valve prolapse, even with murmur • Mitral regurgitation, mitral stenosis, aortic regurgitation aortic stenosisaortic regurgitation, aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), atrial septal defect (ASD) MTB S2CK  ‐ p. 32 Lyme Disease Lyme Disease/Definition  • Arthropod-borne • Spirochete: Borrelia burgdorferi • What is the most common manifestation? • Fever & Rash What is the most common manifestation if• What is the most common manifestation if untreated? • Joint pain • Also: Cardiac or neurologic disease MTB S2CK  ‐ p. 33 28 Lyme Disease/Etiology  • Transmitted by deer tick (Ixodes scapularis) • Tick very small • Only 20% patients recall bite MTB S2CK  ‐ p. 33 © Richard Usatine, M.D. Used with permission Lyme Disease/Etiology  • Patients recall being outdoors • Hiking or camping Experimental models: • Tick must be attached for at least 24 hours in order to transmit organismhours in order to transmit organism MTB S2CK  ‐ p. 33 Lyme Disease/Etiology  • Ixodes tick • Northeast states: • Connecticut (where the town of Lyme gave the disease its name) • Massachusetts • New York • New Jersey MTB S2CK  ‐ p. 33 cdc.gov Lyme Disease/Presentation Rash: Most common manifestation (85% - 90%) • Occurs 5-14 days after bite • Fever often present MTB S2CK  ‐ p. 33 Lyme Disease/Presentation “Erythema migrans” • Round, red • Pale center • Target or bull’s-eye MTB S2CK  ‐ p. 33‐34 Target-shaped rash of Lyme disease or erythema migrans. Source: Nishith Patel. Lyme Disease/Presentation • Joint pain 60% without treatment • “Oligoarthritis” = “few joints” • Joint fluid: ~ 25,000 WBCs/μL • Similar number to gout, pseudogout and i f timany infections MTB S2CK  ‐ p. 33 The knee is the most commonly affected joint in Lyme disease. 29 Lyme Disease/Presentation • Neurological manifestations 10% - 15% • CNS or peripheral • Meningitis, encephalitis, or CN palsy MTB S2CK  ‐ p. 33 Bell’s palsy or 7th CN is most common neurological manifestation of Lyme disease. Lyme Disease/Presentation • Cardiac: 4% - 10% • Any part of myocardium or pericardium • Myocarditis or ventricular arrhythmia MTB S2CK  ‐ p. 33 Transient AV block is the most common cardiac manifestation in Lyme disease. Lyme Disease/Diagnostic Tests  • Typical rash doesn’t need serologic testing to start treatment Serologic testing for Lyme is essential for: • Joint • Neurologicg • Cardiac manifestations • Most 7th CN palsy, arthralgia & AV block are not caused by Lyme • Testing is with IgM, IgG, ELISA, Western blot, and PCR testing MTB S2CK  ‐ p. 34 Lyme Disease/Treatment Manifestation Treatment Asymptomatic tick bite Rash No treatment  routinely Doxycycline  Amoxicillin MTB S2CK  ‐ p. 34 Joint, 7th CN palsy Cardiac and neurologic  manifestations other than 7th CN  palsy Doxycycline Amoxicillin IV ceftriaxone  Asymptomatic Tick Bite Bites without symptoms rarely need treatment Who DOES need treatment? • Single dose of doxycycline Within 72 hours of tick bite when:• Within 72 hours of tick bite when: – Ixodes scapularis clearly identified as tick – Tick attached for > 24-48 hours – Engorged nymph-stage tick – Endemic area MTB S2CK  ‐ p. 34 HIV/AIDS  30 HIV/AIDS/Definition • A retrovirus infecting CD4 (T-helper) cells • CD4 cells drop from normal (600-1000) at a rate of 50 to 100/year untreated • 5 and 10 years before clinical• 5 and 10 years before clinical manifestations • Not HIV itself that leads to death • Low CD4 leads to illness MTB S2CK  ‐ p. 35 HIV life cycle Source: nih.gov HIV/AIDS/Etiology Transmitted by: • IDU • Sex, particularly men who have sex with men • Transfusion (extremely rare since 1985) • PerinatalPerinatal • Needle stick or blood-contaminated sharp instrument injury MTB S2CK  ‐ p. 35 Kissing is not proven to transmit HIV. Risk of Transmission of HIV  Without Prophylactic Treatment  Mode of  transmission Percentage of risk with each event Vaginal transmission Oral sex  1:3000–1:10,000 for insertive intercourse  1:1000 for receptive intercourse  1:1000 for receptive fellatio with ejaculation  MTB S2CK  ‐ p. 35 Needle stick injury  Anal sex  Mother to child Unclear for insertive fellatio or cunnilingus 1:300 1:100 for receptive anal intercourse 25%–30% perinatal transmission without  medication  HIV/AIDS/Presentation • Infections when CD4 drops < 50/μL • PCP < 200/μL • CD4 > 200/μL (few infections occur) • Infections > 200/μL are: – Varicella zoster (shingles) – Herpes simplex – TB – Oral and vaginal candidiasis – Bacterial pneumonia MTB S2CK  ‐ p. 35 HIV/AIDS/Diagnostic Tests  • Best initial test: ELISA test • Confirmed with Western blot Infected infants: • Diagnose with PCR or viral culture • ELISA testing is unreliable in infants • Maternal HIV antibodies are present for up to 6 months after delivery MTB S2CK  ‐ p. 36 31 Viral Load Testing (PCR‐RNA level)  • Measures response to therapy • Decreasing levels good • Detect treatment failure • Rising levels bad • Diagnoses HIV in babies MTB S2CK  ‐ p. 36 Viral Load Testing (PCR‐RNA level)  • The goal of therapy is to drive down viral load • Undetectable levels (< 50/μL): CD4 will rise • CD4 rises = Opportunistic infections• CD4 rises = Opportunistic infections stop • Life expectancy when viral load is undetectable by PCR-RNA is equal in duration to HIV-negative person MTB S2CK  ‐ p. 36 Viral Resistance Testing (Genotyping)  • Perform prior to initiating antiretroviral medications • Decreases likelihood of starting medication to which patient’s virus is resistant Resistance testing: Evaluates treatment failure • Guides choice of medications • Select 3 drugs from 2 different classes to which patient’s virus is susceptible MTB S2CK  ‐ p. 36 HIV/AIDS/Treatment  • For HIV: Treatment is initiated when: • CD4 < 500/μL or • Viral load is very high (>100,000/μL) or • Opportunistic infection occurs MTB S2CK  ‐ p. 36 HIV/AIDS/Treatment  Treatment failure first manifests with rising PCR- RNA viral load MTB S2CK  ‐ p. 36 RNA viral load Choice of Initial Antiretroviral Medication  • Initial drug regimen: • Emtricitabine, Tenofovir, and Efavirenz USMLE Step 2 CK doesn’t test MTB S2CK  ‐ p. 36 USMLE Step 2 CK doesn t test dosing 32 Choice of Initial Antiretroviral Medication  Treatment failure: • Rising viral load • CD4 count decreases or fails to rise • CD4 changes are slower than changes in viral load Alternate Drug Regimens • If emtricitabine/tenofovir/efavirenz cannot be used because of resistance alternate regimens are based on combination of 3 drugs from at least 2 different classes MTB S2CK  ‐ p. 37 Antiretroviral First‐line Medications by Class  Nucleoside and  nucleotide reverse  transcriptase  inhibitors (RTIs)  Non‐ nucleoside  RTIs  Protease inhibitors  • Zidovudine • Didanosine • Efavirenz • Etravirine • Ritonavir • Saquinavir • Lopinavir • Atazanavir MTB S2CK  ‐ p. 37 • Stavudine • Lamivudine  • Emtricitabine • Abacavir • Tenofovir • Nevirapine • Nelfinavir • Amprenavir • Fosamprenavir • Indinavir • Tipranavir • Darunavir Additional Classes of Second‐line Agents  • Used with drug resistance to multiple classes of first-line agents • Entry inhibitors: – Enfuvirtide – Maraviroc • Integrase inhibitor:Integrase inhibitor: – Raltegravir MTB S2CK  ‐ p. 37 USMLE Step 2 CK won’t require you to know details of efficacy differences between classes. Postexposure Prophylaxis  • All significant needle stick injuries • Sexual exposures • Bites • Give 4 weeks of combination therapy • Urine & stool aren’t an indication for postexposure prophylaxis (PEP) MTB S2CK  ‐ p. 37 Postexposure Prophylaxis  Postexposure prophylaxis isn’t routinely indicated for needle stick injury if HIV MTB S2CK  ‐ p. 37 status of needle is unknown Adverse Effects of HIV Medications  Drug Adverse effect Zidovudine Stavudine and didanosine Abacavir Anemia Peripheral neuropathy and pancreatitis Hypersensitivity, Stevens‐Johnson  MTB S2CK  ‐ p. 38 Protease inhibitors Indinavir Tenofovir Reaction Hyperlipidemia, hyperglycemia Nephrolithiasis Renal insufficiency 33 Prevention of Perinatal Transmission Pregnant Patients If already on antiretroviral medications • Continue same treatment If pregnant and not already on di timedications • Start combination antiretrovirals • Only Efavirenz is NOT used in pregnancy MTB S2CK  ‐ p. 38 Prevention of Perinatal Transmission After Delivery for Mother CD4 > 500 and she doesn’t need them • Stop after delivery CD4 < 500 or viral load highCD4 < 500 or viral load high • Continue after delivery Baby Zidovudine during delivery (intrapartum) AND For 6 weeks after to help prevent transmission MTB S2CK  ‐ p. 38 Indications for Antiretrovirals  During Pregnancy Condition Action Patient on antiretrovirals at  the time of pregnancy Continue same medications,  except switch efavirenz to   protease inhibitor MTB S2CK  ‐ p. 38 Not on antiretrovirals,  CD4 low or viral load high  Not on antiretrovirals, CD4 high and viral load low Initiate antiretrovirals  immediately. Continue after  delivery Antiretrovirals immediately,  stop them in mother after  birth  Cesarean Delivery for HIV‐Positive Mothers  • Viral load >1000 μL: Perform Cesarean delivery • Everyone: Intrapartum zidovudine MTB S2CK  ‐ p. 39 Fully controlled HIV (viral load undetectable) gives 1 Nephrology Emma Holliday MDEmma Holliday, MD Resident Physician  Radiation Oncology University of Texas MD Anderson Cancer Center Diagnostic Tests  in Nephrology UrinalysisUrinalysis White Blood Cells Hematuria Cytoscopy Casts Urinalysis • Measures: – Protein – WBCs or leukocyte esterase – RBCs – Specific gravity and pH – NitritesNitrites Pyuria with positive nitrites = UTI MTB S2CK  ‐ p. 299 Dipstick vs. Urinalysis • Both give some quantitative values • Dipstick described as direct (e.g., 300 mg protein) or scale number: 0, 1+, 2+, 3+, or 4+ • Microscopic urinalysis reports number of cells/high- powered field • Don’t worry about the precise scale • Every USMLE Step 2 CK test comes with a range of normal values attached to assess severity MTB S2CK  ‐ p. 299 Urinalysis/Protein • Renal tubules secrete slight amounts of Tamm- Horsfall protein – Should be < 30 to 50 mg/24 hours • Greater amounts of protein associated with either tubular disease or glomerular disease • Very large amounts of protein excreted withVery large amounts of protein excreted with glomerular disease MTB S2CK  ‐ p. 300 1+ proteinuria ~ 1g/day 2+ proteinura ~ 2g/day 3+ proteinuria ~ 3g/day 4+ proteinuria ~ 4g/day Urinalysis/Protein • 2 - 10% of population has transient proteinuria • Benign reasons for proteinuria: – Orthostatic proteinura or physical exertion If symptoms of proteinuria - best initial test? Urinalysis/Dipstick MTB S2CK  ‐ p. 300 initial test? If positive, order urine protein to creatinine ratio or 24 hour urine collection Renal biopsy Most accurate for determining etiology? 2 Urinalysis/Proteinuria Limitations of dipstick for proteinuria: • Only detects albumin • Can’t detect Bence Jones protein – Present in multiple myeloma – Best test for Bence Jones proteinuria is UPEP (urine protein electrophoresis) MTB S2CK  ‐ p. 301 protein electrophoresis) • Can’t detect very low amounts of protein Urinalysis/Microalbuminuria • Microalbuminuria –Tiny amounts of protein too small to detect on UA • An important screening test in diabetic patientspatients –Should be performed yearly • Long-term microalbuminuria –Leads to worsening renal function in diabetic patient and should be treated MTB S2CK  ‐ p. 301 Diabetic patient is evaluated, UA shows no protein. Microalbuminuria is detected (level between 50 - 300 mg/24 hours). What’s the next best step in management? a. Enalapril b Kidney biopsy  Extreme! We know the etiology alreadyb. Kidney biopsy c. Hydralazine d. Renal consultation e. Low-protein diet f. Repeat UA annually and treat when trace protein is detected MTB S2CK  ‐ p. 301 Extreme! We know the etiology already Less effective & with more adverse effects NEVER consult on Step 2 Bad for glycemic control Starting early will delay disease progression Pyuria • White blood cells in urine: – Inflammation – Infection – Allergic interstitial nephritis • Neutrophils can’t be distinguished from eosinophils on UAon UA • Neutrophils indicate infection (UTI or urethritis) • Eosinophils indicate allergic or acute interstitial nephritis (NOT NSAID-induced renal disease) MTB S2CK  ‐ p. 301 Wright and Hansel stains detect eosinophils in the urine. Hematuria Etiology: • Stones • Coagulopathy • Infection (cystitis, pyelonephritis) • Cancer C T t t ( l h h id )• Cancer Treatments (cyclophosphamide) • Trauma • Glomerulonephritis • “False positive” = hemoglobinuria or myoglobinuria Dysmorphic RBCs = glomerulonephritis MTB S2CK  ‐ p. 301‐302 Woman is admitted with trauma and dark urine. The dipstick is markedly positive for blood. What is the best initial test? a. Microscopic examination of urine b. Cystoscopy c Renal ultrasound  Best test for hydronephrosis Overkill - best test to look for bladder mass c. Renal ultrasound d. Renal/bladder CT scan e. Abdominal X-ray f. Intravenous pyelogram MTB S2CK  ‐ p. 302 Most accurate test for stones Best test for ileus or to detect free air Never the right answer - slow test uses nephrotoxic contrast Best test for hydronephrosis 3 When Is Cystoscopy the Answer? • When there’s hematuria without infection or prior trauma and: –The renal ultrasound or CT doesn’t show etiology –Bladder sonography shows mass forBladder sonography shows mass for possible biopsy MTB S2CK  ‐ p. 302 Cystoscopy is the most accurate test of the bladder. Casts • Microscopic collections of material clogging up the tubules and being excreted in urine Type of cast • Red cell • White cell Association • Glomerulonephritis • Pyelonephritis MTB S2CK  ‐ p. 302‐303 • Eosinophil • Hyaline • Broad, waxy • Granular, “muddy- brown” • Acute interstitial nephritis • Dehydration • Chronic renal disease • Acute tubular necrosis (are dead tubular casts) Acute Kidney Injury Acute Tubular Necrosis Hepatorenal Syndromep y Atheroemboli Acute (Allergic) Interstitial Nephritis Analgesic Nephropathy Acute Kidney Injury • Acute kidney injury (AKI) – Decrease in creatinine clearance – Results in sudden rise in BUN and creatinine • The definition is not based on specific values of BUN and creatinine • Categories: – Prerenal azotemia (decreased perfusion) – Postrenal azotemia (obstruction) – Intrinsic renal disease (ischemia and toxins) MTB S2CK  ‐ p. 303 Acute Kidney Injury Prerenal • Hypotension - Sepsis - Anaphylaxis Bleeding • BPH/Prostate cancer • Ureteral stone • Cervical cancer • Urethral stone • Neurogenic bladder Intrinsic Renal Post Renal • ATN - Toxins • NSAIDs • AG, ampho • Cis cyclosporine- Bleeding - Dehydration • Hypovolemia - Diuretics - Burns - Pancreatitis - ↓pump fxn - Low albumin - Cirrhosis • Renal artery stenosis • Neurogenic bladder • Retroperitoneal fibrosis (chemo or XRT) • Cis, cyclosporine - Prolonged ischemia • AIN - PCN, sulfa • Rhabdo/hemoglobinuria • Contrast • Crystals • Bence-Jones proteins • Post-strep infection • MTB S2CK  ‐ p. 303‐304 Acute Kidney Injury/Presentation • AKI usually = asymptomatic rise in BUN and creatinine; when symptomatic: – Nausea and vomiting – Fatigue/malaise – Weakness – SOB, edema (fluid overload) • Very severe disease presents with: – Confusion – Arrhythmia from hyperkalemia and acidosis – Sharp, pleuritic chest pain from pericarditis MTB S2CK  ‐ p. 304‐305 4 Acute Kidney Injury/Diagnostic Tests • The best initial test is... –BUN and creatinine • Nonfunctional kidneys – creatinine rises ~ 1 point/day (1 mg/dL) If the BUN creatinine ratio is > 20 1 the• If the BUN:creatinine ratio is > 20:1 the etiology is either prerenal or postrenal damage • Intrinsic renal disease ratio closer to 10:1 MTB S2CK  ‐ p. 305 Acute Kidney Injury/Diagnostic Tests • What is the best initial imaging test? – Renal sonogram because it isn’t invasive and doesn’t need contrast • Kidney biopsy is rarely the right answer for AKI MTB S2CK  ‐ p. 305 Acute Kidney Injury/Diagnostic Tests • When cause is unclear “next best diagnostic step” is: – Urinalysis – Urine sodium (UNa) – Fractional excretion of sodium (FENa) or urea (FEUrea) – Urine osmolality If all of these are choices always go with urinalysis first MTB S2CK  ‐ p. 306 Acute Kidney Injury/Diagnostic Tests Urine Sodium and Fractional Excretion of Sodium • Normal kidney: – ↓ blood pressure  ↑ aldosterone – ↑ aldosterone ↑ sodium reabsorption ↓ sodium in the urine (< 20) • Damaged kidney (e.g., ATN):Damaged kidney (e.g., ATN): – Kidneys can’t reabsorb Na appropriately (> 20) MTB S2CK  ‐ p. 306 Prerenal azotemia: low UNa (below 20) = low FENa (less than 1%) You can answer all the questions on USMLE Step 2 CK without knowing the mathematical formula for FENa. Acute Kidney Injury/Diagnostic Tests Urine Osmolality • Normal kidney: –↓ intravascular volume  ↑ ADH –↑ ADH  ↑ water reabsorption at collecting duct  ↑ urine osmolaritycollecting duct  ↑ urine osmolarity • Damaged kidney (e.g., ATN): –Kidneys can’t concentrate urine appropriately - will see Osm similar to blood (~300mOsm) MTB S2CK  ‐ p. 306 20-year-old African-American man has screening test for sickle cell. He’s found to be heterozygous (trait or AS) for sickle cell. What is the best advice for him? a. Nothing needed until he has a painful crisis b. Avoid dehydration Sickle cell trait rarely experience pain crises y c. Hydroxyurea d. Folic acid supplementation e. Pneumococcal vaccination MTB S2CK  ‐ p. 307  Only if > 4 pain crises per year. Indicated if hemolysis present (high RBC turnover)Indicated if functionally asplenic 5 Classification of Acute Renal Failure Test Prerenal azotemia Acute tubular necrosis BUN:Creatinine Urine Sodium (UNa) F ti l ti > 20:1 1% MTB S2CK  ‐ p. 307 Fractional excretion of sodium (FENa) Urine osmolality (UOsm)  500  mOsm/kg > 1% 1% 1.035 (high) b. 58 (high) >1% 1.005 (low) c. 5 (very low) 1% 1.005 (low) MTB S2CK  ‐ p. 309  Spasm of afferent arteriole leads to ↑ reabsorption of Na (and thus water)  very concentrated urine (↑ specific gravity) Extra‐Difficult Question A patient with extremely severe myeloma with a plasmacytoma is admitted for combination chemotherapy. Two days later creatinine rises. What is the most likely cause? a. Cisplatin b Hyperuricemia Takes 5-10 daysb. Hyperuricemia c. Bence-Jones proteinuria d. Hypercalcemia e. Hyperoxaluria MTB S2CK  ‐ p. 309  Can cause renal insufficiency but would not get worse with treatment Oxalate crystals can be present in urine in cases of bowel resection 6 Extra‐Difficult Question What would’ve prevented this event? • Allopurinol, hydration, and rasburicase • Given prior to chemotherapy to prevent renal failure from tumor lysis syndrome MTB S2CK  ‐ p. 309 Extra‐Difficult Question Suicidal patient ingests an unknown substance and develops renal failure 3 days later. Her calcium level is low and urinalysis shows an abnormality. What did she take? a. Aspirin b. Acetaminophen Doesn’t affect Ca levels or cause crystals Hepatotoxicp c. Ethylene glycol d. Ibuprofen e. Opiates f. Methanol MTB S2CK  ‐ p. 310  Constrict afferent arteriole  ATN and papillary necrosis p Affects retinal inflammation not AKI Can cause FSGS, but not AKI Acute Tubular Necrosis/Toxins 3 things increase risk of toxic/insult ATN: • Hypoperfusion of kidney • Underlying renal insufficiency – Hypertension – Diabetes– Diabetes • Older age MTB S2CK  ‐ p. 310 We lose 1% of renal function every year past age of 40. Acute Tubular Necrosis Summary of Causes: • Slow onset (5 - 10 days)  Drug-related injury – Aminoglycosides, amphotericin, cisplatin, vancomycin, acyclovir, cyclosporine – Dose dependent • ↓Mag  ↑risk for aminoglycoside and cisplatin• ↓Mag  ↑risk for aminoglycoside and cisplatin • Immediate toxicity (24 – 48 hrs)  Contrast media – Best prevented with saline hydration – N-acetylcysteine and sodium bicarbonate aren’t consistently proven as beneficial MTB S2CK  ‐ p. 310 Acute Tubular Necrosis Summary of Causes: • Hemoglobin and myoglobin • Hyperuricemia • Ethylene Glycol • Multiple Myeloma • NSAIDs MTB S2CK  ‐ p. 310 Rhabdomyolysis • Etiology? –Trauma, prolonged immobility, snake bites, seizures, and crush injuries • The best initial test? UA (dipstick AND microscopic analysis)–UA (dipstick AND microscopic analysis) • Characteristic findings? –Blood is positive on dipstick but NO RBCs are seen on microscopic exam MTB S2CK  ‐ p. 311 7 Rhabdomyolysis • Most specific lab test? –Urine myoglobin • Abnormal lab findings? –↑ Creatine phosphokinase (CPK) H k l i–Hyperkalemia –Hyperuricemia –Hyperphosphatemia –Hypocalcemia MTB S2CK  ‐ p. 311 Rhabdomyolysis Treat with: • Saline hydration • Mannitol • Bicarbonate MTB S2CK  ‐ p. 311 Don’t treat hypocalcemia in rhabdomyolysis if asymptomatic. In recovery, the calcium will come back out of muscles. A man comes to the ED after a triathlon followed by status epilepticus. He takes simvastatin at triple the recommended dose. His muscles are tender and urine is dark. IV fluids are started. What is the next best step in management? a. CPK level Would suggest rhabdo as cause, but not life b. EKG c. Potassium replacement d. Urine dipstick e. Urine myoglobin MTB S2CK  ‐ p. 311‐312  gg ,threatening complications. Would be fatal Same reason as A Same reason as A Acute Tubular Necrosis/Treatment • No therapy proven to benefit ATN • Patients should be managed with – Hydration, if they’re volume depleted and correction of electrolyte abnormalities • Diuretics increase urine output, but don’t change overall outcome MTB S2CK  ‐ p. 312 More urine output with diuretics doesn’t mean renal failure is reversing. Acute Tubular Necrosis/Treatment • Answering treatment questions for ATN is based on recognizing the most common wrong answers: – Low-dose dopamine – Diuretics – Mannitol – Steroids • All these are ineffective in reversing ATN Correct underlying cause MTB S2CK  ‐ p. 312 Acute Tubular Necrosis/Treatment When Is Dialysis the Answer? • Dialysis is initiated if there’s: – Fluid overload – Encephalopathy – PericarditisPericarditis – Metabolic acidosis – Hyperkalemia MTB S2CK  ‐ p. 312 A- acidosis E- electrolytes I- intoxications O- overload of volume U-uremia 8 Acute Tubular Necrosis/Rhabdomyolysis Patient develops ATN from gentamicin. She’s vigorously hydrated and treated with high doses of diuretic, low-dose dopamine, and calcium acetate as a phosphate binder. Urine output increases, but she still progresses to end-stage renal failure. She also becomes deaf. What caused her hearing loss? a. Hydrochlorothiazide b. Dopamine c. Furosemide d. Chlorthalidone e. Calcium acetate MTB S2CK  ‐ p. 313  No otoxicity No ototoxicity No ototoxicity No ototoxicity Hepatorenal Syndrome Renal failure developing secondary to liver disease • Kidneys normal • Look for: – Severe liver disease (cirrhosis) – New-onset renal failure with no other explanation – Very low urine sodium (> 10 – 15 mEq/dL) – FeNa < 1% – Elevated BUN:creatinine ratio (> 20:1) • Treat with: – Albumin, midodrine, octreotide MTB S2CK  ‐ p. 313 Atheroemboli/Etiology • Can occur during catheter procedures: – Cardiac catheterization, angiogram • Emboli can go to: – Kidney, leading to AKI – Eye – Cutaneous vessles  livedo reticularis • Lab findings: – Eosinophilia/Eosinophiluria, ↓ compliment, ↑ ESR • Most accurate test: – Biopsy  cholesterol crystals MTB S2CK  ‐ p. 313‐314 • Livedo reticularis Atheroemboli/Etiology Peripheral pulses are normal in atheroemboli MTB S2CK  ‐ p. 314 Source: Farshad Bagheri, MD atheroemboli. They’re too small to occlude vessels such as the radial or brachial artery. Acute (Allergic) Interstitial Nephritis • Antibodies and eosinophils attack cells lining tubules • Reaction to drugs (70%), infection, and autoimmune disorders – Penicillins and cephalosporins – Sulfa drugs (including diuretics like furosemide and thiazides which are sulfa derivatives)thiazides, which are sulfa derivatives) – Phenytoin – Rifampin – Quinolones – Allopurinol – PPI MTB S2CK  ‐ p. 314‐315 The medications that cause AIN are the same as those that cause: • Drug allergy and rash • Stevens-Johnson syndrome • Toxic epidermal necrolysis • Hemolysis Acute (Allergic) Interstitial Nephritis Presentation: “What Is the Most Likely Diagnosis?” Look for acute renal failure (rising BUN and creatinine) with: • Fever (80%) • Rash (50%) • Arthralgias• Arthralgias • Eosinophilia and eosinophiluria (80%) • BUN/Cr ratio < 20:1 • WBC and RBC in urine What is the most accurate test?  Wright/Hansel stain to identify eosinophiluria MTB S2CK  ‐ p. 315‐316 9 Acute (Allergic) Interstitial Nephritis Treatment • AIN usually resolves spontaneously with stopping drugs or controlling infection • Severe disease is managed with dialysis, which may be temporary • When creatinine continues to rise after stopping the drug, giving glucocorticoids (prednisone, hydrocortisone, methylprednisolone) is the answer MTB S2CK  ‐ p. 316 Analgesic Nephropathy Analgesic nephropathy presents with: • ATN from direct toxicity to tubules • AIN • Membranous glomerulonephritis • Papillary necrosis MTB S2CK  ‐ p. 316 Analgesic Nephropathy Presentation • Vascular insufficiency of kidney from inhibiting prostaglandins – Prostaglandins dilate the afferent arteriole – NSAIDs constrict the afferent arteriole and decrease renal perfusionp – Asymptomatic in healthy patients – When patients are older and have underlying renal insufficiency from diabetes and/or hypertension, NSAIDs can tip them over into clinically apparent renal insufficiency due to direct toxicity to tubules MTB S2CK  ‐ p. 316 Papillary Necrosis Sloughing off renal papillae Etiology • NSAIDs or sudden vascular insufficiency  – Death of cells in papillae and their dropping off the internal structure of kidney • Occurs with underlying kidney damage: – Sickle Cell – DM – Urinary obstruction – Chronic pyelonephritis MTB S2CK  ‐ p. 316 Papillary Necrosis • Clinical presentation: – Fever, hematuria, and sudden onset flank pain – Looks like pyelonephritis • Best initial test: – UA • Most accurate test: – CT scan • Treatment: – No specific therapy MTB S2CK  ‐ p. 317 Differences between Pyelonephritis and Papillary Necrosis Pyelonephritis Papillary necrosis Onset Symptoms Urine culture Few days Dysuria Positive Few hours Necrotic material in urine Negative MTB S2CK  ‐ p. 317 Urine culture CT scan Treatment Positive Diffuse swollen kidney Antibiotics, such as ampicillin/gentamicin  or fluoroquinolones Negative “Bumpy” contour of kidney interior No treatment 10 Glomerular Diseases Goodpasture Syndrome IgA Nephropathy Postinfectious Glomerulonephritis Alport Syndrome Polyarteritis Nodosa Lupus Nephritis Amyloidosis Nephrotic Syndrome Glomerular Diseases • Chronic • Immune mediated • All nephrotic Need biopsy • Acute • Caused by toxins • Not nephrotic No biopsy Tubular Disease • Need biopsy • Often steroids, cyclophosphamide, mycophenolate MTB S2CK  ‐ p. 318 • No biopsy • No steroids or immunosuppressives Glomerular Diseases/Diagnostic Tests All forms of glomerulonephritis have: • UA with hematuria • “Dysmorphic” red cells (deformed as they “squeeze” through an abnormal glomerulus) • Red cell casts • Urine sodium and FENa are low • Proteinuria MTB S2CK  ‐ p. 318 The amount of proteinuria is the main difference between glomerulonephritis and nephrotic syndrome. Goodpasture Syndrome • Lung + kidney involvement • No upper respiratory tract involvement Diagnosis • Best initial test: – Antiglomerular basement membraneAntiglomerular basement membrane antibodies • Most accurate test: – Lung or kidney biopsy MTB S2CK  ‐ p. 319 Kidney biopsy in Goodpasture syndrome shows “linear deposits.” Goodpasture Syndrome Commons.wikimedia. Used with permissionMTB S2CK  ‐ p. 319 Goodpasture Syndrome Diagnosis • Anemia from hemoptysis • CXR abnormal, but not diagnostic Treatment • Plasmapheresis • Steroids • Cyclophosphamide MTB S2CK  ‐ p. 319 11 IgA nephropathy (Berger disease)  • MCC of acute glomerulonephritis in U.S. • Presentation: Gross hematuria 1 to 2 days after an upper respiratory tract infection • IgA levels ↑ in 50% • Most accurate test = kidney biopsyy p y • No treatment: ½ will resolve, ½ progress to ESRD • Steroids and ACE-inhibitors may help severe proteinuria MTB S2CK  ‐ p. 319‐320 Postinfectious Glomerulonephritis • Most common infection is Streptococcus • Follows throat infection or skin infection (impetigo) by 1 to 3 weeks Presentation • Cola-colored urine • Edema (periorbital) • HTN • Oliguria MTB S2CK  ‐ p. 320 Commons.wikimedia, James Heilman, MD. Used with permission Postinfectious Glomerulonephritis Diagnostic Tests • 1st - UA  glomerulonephritis • 2nd - Antistreptolysin O (ASO) titers and anti-DNAse antibody titers M t t Bi• Most accurate - Biopsy MTB S2CK  ‐ p. 320 Postinfectious Glomerulonephritis Commons.wikimedia. Used with permissionMTB S2CK  ‐ p. 320 Postinfectious Glomerulonephritis Treatment • Management of strep infection does not reverse glomerulonephritis • Use supportive therapies such as: A tibi ti–Antibiotics –Diuretics to control fluid overload MTB S2CK  ‐ p. 320 12 Alport Syndrome • Congenital defect of collagen • Results in glomerular disease combined with: –Sensorineural hearing loss Visual disturbance from loss of collagen–Visual disturbance from loss of collagen fibers that hold lens of eye in place • There’s no specific therapy to reverse this defect of type IV collagen MTB S2CK  ‐ p. 320 Polyarteritis Nodosa Definition • Systemic vasculitis of small and medium-sized arteries • Spares lungs A i t d ith h titi B• Associated with hepatitis B MTB S2CK  ‐ p. 321 PAN is nonspecific. There’s no single finding that allows you to answer the “most likely diagnosis” question. Polyarteritis Nodosa/Presentation The most common organ systems involved are: • GI – Abdominal pain, bleeding, nausea, and vomiting occur • Neuro – Peripheral neuropathy or “mononeuritis multiplex.”Peripheral neuropathy or mononeuritis multiplex. • Skin – Petechiae, purpura, ulcers, livedo reticularis • Cardiac – Stroke or MI, particularly in young person MTB S2CK  ‐ p. 321 Polyarteritis Nodosa/Diagnostic Tests Blood tests will show: • Anemia and leukocytosis • ↑ ESR and C-reactive protein • ANCA: Not present in most cases • ANA and rheumatoid factor: Sometimes present in low titerlow titer Angiography • Renal, mesenteric, or hepatic artery showing aneurysmal dilation Biopsy • Most accurate if at symptomatic site MTB S2CK  ‐ p. 321 Polyarteritis Nodosa Treatment • Prednisone and cyclophosphamide ↓ mortality • Treat hepatitis B when it’s found MTB S2CK  ‐ p. 321‐322 Lupus Nephritis SLE can give any degree of renal involvement • Normal • Mild, asymptomatic proteinuria • Membranous glomerulonephritis • Glomerulosclerosis  “scars” kidneys without inflammation leading to ESRD requiring dialysisinflammation leading to ESRD requiring dialysis Diagnosis • Biopsy (tells severity) Treatment • Steroids, cyclophosphamide, mycophenolyate MTB S2CK  ‐ p. 322 13 Amyloidosis Amyloid is an abnormal protein produced in association with: • Myeloma • Chronic inflammatory diseases • Rheumatoid arthritis • Inflammatory bowel disease • Chronic infections MTB S2CK  ‐ p. 322 Amyloid, HIV nephropathy, polycystic kidneys, and diabetes give large kidneys on sonogram and CT scan. Amyloidosis • Most accurate test = biopsy –Apple-green birefringence with Congo red staining • Best treatment = control underlying diseasedisease • 2nd line Treatment = melphalan and prednisone MTB S2CK  ‐ p. 322 Amyloidosis Katsumi M. Miyai, MD, PhD. Regents of the University of California. Used with permission MTB S2CK  ‐ p. 322 Nephrotic Syndrome/Definition • Measure of the severity of proteinuria in association with any form of glomerular disease – > 3.5 g/24 hrs • Liver can no longer increase the production of albumin to compensate for urinary losses • Massive proteinuria leads to:Massive proteinuria leads to: – Edema (periorbital) – Hyperlipidemia – Thrombosis: • From urinary loss of natural anticoagulants protein C, protein S, and antithrombin MTB S2CK  ‐ p. 322 Nephrotic Syndrome/Etiology • MCC = diabetes and hypertension – Any of the glomerular diseases just described Other associations are: • Cancer (solid organ): membranous • Children: minimal change disease • Injection drug use and AIDS: focal-segmental • NSAIDs: minimal change disease and membranous • SLE: Any of them MTB S2CK  ‐ p. 323 Nephrotic Syndrome/Diagnostic Tests • Best initial test = urinalysis • Next best test = albumin/creatinine ratio or 24-hour urine protein collection • Most accurate test = biopsy: – Focal-segmentalFocal segmental – Membranous – Membranoproliferative – Minimal change – Mesangial MTB S2CK  ‐ p. 323 14 Nephrotic Syndrome/Diagnostic Tests By definition, nephrotic syndrome is: • Hyperproteinuria (> 3.5 g/24 hours) • Hypoproteinemia • Hyperlipidemia • Edema MTB S2CK  ‐ p. 324 Nephrotic Syndrome/Treatment Treatment • Best 1st therapy = glucocorticoids • 2nd line = cyclophosphamide • ACE inhibitors or ARBs to control proteinuria • Edema managed with salt restriction andEdema managed with salt restriction and diuretics • Hyperlipidemia is managed with statins as you would any form of hyperlipidemia MTB S2CK  ‐ p. 324 End‐Stage Renal Disease Etiology Presentation Manifestations Treatment Kidney Transplantation End Stage Renal Disease/Definition • Not defined as a particular BUN or creatinine • Loss of renal function  symptoms and laboratory abnormalities known as uremia • Uremia is defined as the presence of: – Metabolic acidosis Peritoneal dialysis and– Fluid overload – Encephalopathy – Hyperkalemia – Pericarditis • Acute indications for dialysis MTB S2CK  ‐ p. 324‐325 Peritoneal dialysis and hemodialysis are equally effective at removing wastes from the body. End Stage Renal Disease Manifestations of Renal Failure • Anemia: Normocytic, normochromic – Loss of EPO • Hypocalcemia: Can’t absorb Ca from GI tract – 25-hydroxy-vitamin D  1,25-dihydroxy-vitamin D • Osteodystophy: Demineralized bones, soft/weak – Secondary hyperparathyroidism • Hyperphosphatemia: Can’t excrete – ↑PTH  release of PO4 from bones • Hypermagnesemia: Can’t excrete MTB S2CK  ‐ p. 325 End Stage Renal Disease Manifestations of Renal Failure (cont’d) • Bleeding: – No degranulation  can’t aggregate • Infection: – No degranulation  can’t fight infection • Accelerated atherosclerosis: – Abnormal WBCs cannot clear lipid accumulation from arteries • Pruritus: – Unclear reasoning; urea accumulating in skin causes itching MTB S2CK  ‐ p. 325 15 End Stage Renal Disease Manifestations of Renal Failure (cont’d) • Endocrinopathy: –Women are anovulatory –Men have  testosterone  erectile dysfunctiondysfunction –Hyperinsulinemia and insulin resistance • Either hyper- or hypoglycemic MTB S2CK  ‐ p. 325 Treatment of ESRD Manifestations Manifestation Treatment Anemia Hypocalcemia Bleeding Pruritus Erythropoietin replacement and  iron supplementation Replace vitamin D and calcium DDAVP increases platelet function Dialysis and ultraviolet light MTB S2CK  ‐ p. 325 Hyperphosphatemia Hypermagnesemia Atherosclerosis Endocrinopathy Oral binders, see Hyperphos Rx Restriction of high‐Mg foods, laxatives,  and antacids Dialysis Dialysis, estrogen & testosterone  replacement End Stage Renal Disease Treatment of Hyperphosphatemia • Medications: –Calcium acetate –Calcium carbonate Use sevelamer and–Sevelamer –Lanthanum MTB S2CK  ‐ p. 326 Use sevelamer and lanthanum when calcium level is high. Never use aluminum containing phosphate binders. Aluminum causes dementia. End Stage Renal Disease Kidney Transplantation • Only 50% of ESRD patients will be suitable for transplantation • The donor doesn’t have to be alive or related although these are both betterrelated, although these are both better MTB S2CK  ‐ p. 326 HLA-identical, related donor kidneys last 24 years on average. End Stage Renal Disease 1 year 3 years 5 years Living, related donor Deceased donor 95% 90% 88% 78% 72% 58% Survival by Method MTB S2CK  ‐ p. 326 Deceased donor Dialysis alone Diabetics on dialysis 90% Variable Variable 78% Variable Variable 58% 30‐40% 20% Thrombotic thromobocytopenic purpura  and Hemolytic Syndrome • Different variants, same disease • TTP is associated with HIV, cancer, and drugs (e.g., cyclosporine, ticlopidine, and clopidogrel) • HUS is MC in children and the most frequently tested association is E. coli 0157:H7 and Shigella MTB S2CK  ‐ p. 326 16 Thrombotic thromobocytopenic purpura  and Hemolytic Syndrome • Both TTP and HUS are associated with: – Intravascular hemolysis – Renal insufficiency – Thrombocytopenia TTP l i i d i h• TTP also is associated with: – Neurological symptoms – Fever • The hemolysis is visible on smear with schistocytes, helmet cells, and fragmented red cells MTB S2CK  ‐ p. 326 Thrombotic thromobocytopenic purpura  and Hemolytic Syndrome MTB S2CK  ‐ p. 327 Source: Abhay Vakil, MD. Thrombotic thromobocytopenic purpura and  Hemolytic Syndrome • Most cases of HUS from E. coli will resolve spontaneously • Plasmapheresis is generally urgent in TTP • Severe HUS also needs urgent plasmapheresis • If plasmapheresis is not one of the choices use• If plasmapheresis is not one of the choices, use infusions of fresh frozen plasma (FFP) • Steroids don’t help MTB S2CK  ‐ p. 327 Platelet transfusion is never the correct choice for TTP or HUS Cystic Disease Simple versus Complex Cysts Polycystic Kidney Diseasey y y Benign (Simple) vs. Malignant (Complex) Cysts Simple Cyst Complex Cysts Echogenicity Walls Echo free Smooth, thin Mixed echogenicity Irregular, thick MTB S2CK  ‐ p. 326 Demarcation Transmission Sharp Good through to back Lower density on back wall Debris in cyst Polycystic Kidney Disease Polycystic kidney disease (PCKD) presents with: • Pain • Hematuria • Stones • Infection • HTN MTB S2CK  ‐ p. 328 No therapy exists to prevent or reverse cysts of any type. 17 What is the MCC of death from PCKD? a. Intracerebral hemorrhage b. Stones c. Infection d Malignancy Only 10-15% have cerebral aneurysms Pyelo is more common but rarely fatal No malignant potential Doesn’t progress Can occur but do not lead to death d. Malignancy e. Renal failure MTB S2CK  ‐ p. 328  No malignant potential. Doesn t progress to RCC Sodium & Potassium  Disorders HypernatremiaHypernatremia Hyponatremia Hyperkalemia Hypokalemia Hypernatremia/Etiology • Loss of free water • Examples are: –Sweating –Burns F–Fever –Pneumonia (insensible losses from hyperventilation) –Diarrhea –Diuretics MTB S2CK  ‐ p. 328 Hypernatremia/Etiology Diabetes Insipidus (DI) • High urinary volume water loss • Insufficient or ineffective ADH • Symptoms – Confusion Sodium disorders – Disorientation – Lethargy – Seizures • If uncorrected, severe hypernatremia causes coma and irreversible brain damage MTB S2CK  ‐ p. 328 Sodium disorders cause CNS problems Diabetes Insipidus (DI) Nephrogenic DI Definition Etiology Loss of ADH  effect Lithium Central DI Loss of ADH  production CNS disorders:  MTB S2CK  ‐ p. 328‐329 Demeclocycline Chronic kidney  disease Hypokalemia Hypercalcemia Stroke Tumor Trauma Hypoxia Infection Hypernatremia/Diagnostic Tests To distinguish DI from other causes of hypernatremia look for: • Increased urine volume • Decreased urine osmolality D d i di• Decreased urine sodium MTB S2CK  ‐ p. 329 Increased urine volume despite dehydration and hyperosmolality of blood suggests DI 18 Diagnosing DI Continued high volume dilute urine Diabetes Insipidus Water deprivation test Psychogenic Polydipsia Best initial test? ↓urine volume ↑osmolality MTB S2CK  ‐ p. 329 ADH administration test Next best test? Central DI Nephrogenic DI ↓urine volume ↑osmolality Continued high volume dilute urine **Most accurate test = ADH level ↑ NDI ↓ CDI Central DI vs. Nephrogenic DI NDI Polyuria and nocturia Urine osmolality and sodium Yes Low CDI Yes Low  MTB S2CK  ‐ p. 329 Positive water deprivation test Response to ADH ADH level Yes  No High Yes  Yes Low Hypernatremia/Treatment • Fluid loss: – Correct underlying cause of fluid loss • CDI: – Replace ADH (vasopressin also known as DDAVP) • NDI: – Correct potassium and calcium – Stop lithium or demeclocycline – Give hydrochlorothiazide or NSAIDs for those still having NDI despite these interventions MTB S2CK  ‐ p. 330 Hypernatremia/Treatment Complications of Therapy • Cerebral edema: sodium levels brought down too rapidly • Cerebral edema presents with worsening confusion and seizuresworsening confusion and seizures MTB S2CK  ‐ p. 330 Hyponatremia/Etiology Hypervolemia • MCC of hyponatremia with hypervolemic state are: –CHF Nephrotic syndrome–Nephrotic syndrome –Cirrhosis MTB S2CK  ‐ p. 330  Hyponatremia/Etiology Intravascular volume depletion CHF, nephrotic syndrome, cirrhosis Increased ADH levels Stimulated by baroreceptors MTB S2CK  ‐ p. 330 Stimulated by baroreceptors in atria and carotids Free water reabsorption Sodium concentration drops 19 Hyponatremia/Etiology Hypovolemia • Sweating • Burns • Fever • PneumoniaPneumonia • Diarrhea • Diuretics MTB S2CK  ‐ p. 330  Hyponatremia/Etiology Addison’s disease • Loss of adrenal function  loss of aldosterone • Aldosterone causes Na+ reabsorption • If the body loses aldosterone, it loses Na+y , MTB S2CK  ‐ p. 331 Hyponatremia/Etiology Euvolemic Hyponatremia • MCCs: –Pseudohyponatremia (hyperglycemia) –Psychogenic polydipsia H th idi–Hypothyroidism –Syndrome of inappropriate ADH (SIADH) release MTB S2CK  ‐ p. 331 Hyponatremia/Presentation Hyponatremia presents entirely with CNS symptoms: • Confusion • Lethargy • DisorientationDisorientation • Seizures • Coma MTB S2CK  ‐ p. 331 Symptoms of hyponatremia are dependent on how fast it occurs. Hyponatremia/Diagnostic Tests SIADH • High urine osmolality • High urine sodium • Low uric acid level and BUN • Most accurate test is a high ADH level MTB S2CK  ‐ p. 332 Response to Hyponatremia SIADH Urine  osmolality Urine High High (> 40 mEq/L) Normal levels Low  ( 40 mEq/L)Low ( 20 Hyponatremia/Treatment The treatment answer isn’t based on sodium level; it’s MTB S2CK  ‐ p. 332 ; based on the symptoms. Clinical Manifestations of Hyponatremia by Severity Management  Mild  hyponatremia Moderate Restrict fluids Saline and loop Specific  manifestation No symptoms Minimal confusion Degree of  hyponatremia MTB S2CK  ‐ p. 332 Moderate  Severe  Saline and loop  diuretics Hypertonic saline,  conivaptan,  tolvaptan Minimal confusion Lethargy, seizures,  coma Hyponatremia/Treatment Complications of Treatment • Goal: increase in Na is 0.5 to 1 mEq/hour (12 to 24 mEq/day) • If the sodium level is brought up to normal too rapidly  central pontine myelinolysis (osmotic demyelinization occurs) MTB S2CK  ‐ p. 332 Central Pontine Myelinolysis MTB S2CK  ‐ p. 332 Hyperkalemia • Typically defined as [K+] > 5mEq/L Severe hyperkalemia can stop the heart in seconds if MTB S2CK  ‐ p. 332 stop the heart in seconds if the level is high enough. Hyperkalemia/Etiology K > 5mEq/L Pseudo- hyperkalemia Decreased Excretion Increased Release from Tissues MTB S2CK  ‐ p. 333 • Hemolysis • Leukocytosis • Thrombocytosis Repeat the blood sample • Renal failure • Acute or chronic • Low aldosterone state • ACE inhibitors/ARBs • RTA IV • Drugs • Addison disease • Cell lysis • Low insulin • Acidosis • Drugs • Beta blockers • Digoxin • Heparin 21 Hyperkalemia/Presentation • Potassium disorders interfere with muscle contraction and cardiac conductance • Look for: – Weakness – Paralysis when severe – Ileus (paralyzes gut muscles) – Cardiac rhythm disorders MTB S2CK  ‐ p. 333 Hyperkalemia does not cause seizures. Hyperkalemia/Diagnostic Tests • If hyperkalemia is suspected • Most urgent test: – EKG • The EKG in severe hyperkalemia shows: – Peaked T waves – Wide QRS – PR interval prolongation MTB S2CK  ‐ p. 333‐334 Hyperkalemia/Treatment K > 5mEq/L Pseudo- hyperkalemia? EKG Changes? Yes No MTB S2CK  ‐ p. 334 No treatment needed • Calcium chloride or calcium gluconate • Insulin and glucose, inhaled beta agonist • Give bicarbonate if acidosis is the cause • Consider hemodialysis • Kayexalate • Loop diuretics Yes No Hyperkalemia/Treatment When there’s hyperkalemia and an abnormal EKG, the “most appropriate next step” is clearly calcium chloride or gluconate. MTB S2CK  ‐ p. 334 Sodium = CNS symptoms Hyperkalemia = muscular and cardiac symptoms Hypokalemia/Etiology K < 3.5 mEq/L Decreased Intake Shift into cells Renal Losses GI Losses MTB S2CK  ‐ p. 334‐335 Very Rare Kidney can adjust excretion • Alkalosis • Insulin • Β agonists (stimulate Na/K ATPase pump) ↑ aldosterone • Conns • ↓Volume • Cushing’s • Bartter’s • Licorice • Hypomagnesemia • RTA I and II Vomiting Diarrhea Laxatives Hypokalemia/Presentation • Hypokalemia leads to problems with muscular contraction and cardiac conduction • Potassium is essential for proper neuromuscular contraction • Hypokalemia presents with: – Weakness – Paralysis – Loss of reflexes MTB S2CK  ‐ p. 335 Muscular abnormalities may be so severe as to cause rhabdomyolysis. 22 Hypokalemia/Presentation EKG findings • U waves are the most characteristic finding of hypokalemia • Other findings are ventricular ectopy (PVCs), flattened T waves, and ST depression MTB S2CK  ‐ p. 335 Hypokalemia does not cause seizures. Hypokalemia/Treatment • No maximum rate of oral potassium replacement – GI tract cannot absorb potassium faster than the kidneys can excrete it • IV potassium replacement, however, can cause a fatal arrhythmia if it’s done too fasta fatal arrhythmia if it s done too fast – You must allow time for potassium to equilibrate into cells MTB S2CK  ‐ p. 335 IV potassium replacement must be very slow. Patient is admitted with vomiting and diarrhea from gastroenteritis. His volume status is corrected with IV fluids and diarrhea resolves. His pH is 7.40 and serum bicarbonate has normalized. Despite vigorous oral and IV replacement, his potassium level fails to rise. What should you do? a. Consult nephrology b. Magnesium level c. Parathyroid hormone level d. Intracellular pH level e. 24-hour urine potassium level MTB S2CK  ‐ p. 335‐336  Mg needed for PTH release Don’t consult except for procedures! Doesn’t tell you underlying cause or change tx Not MCC Woman with ESRD and G6PD deficiency skips dialysis for a few weeks. She experiences a crush injury during a MVA. She is taking dapsone and has recently eaten fava beans. What is the most urgent step? a. Initiate dialysis b EKG Must look for EKG changes 1stb. EKG c. Bicarbonate administration d. Insulin administration e. Kayexalate f. Urine dipstick g. CPK levels h. Urine myoglobin MTB S2CK  ‐ p. 336  Take 15-20min to work Take hours to work Doesn’t address life threatening complications Acid‐Base Disturbances Renal Tubular Acidosis Urine Anion Gapp Metabolic Acidosis Metabolic Alkalosis Respiratory Acidosis and Alkalosis Non‐anion gap metabolic acidosis (NAGMA) The anion gap is: • Na+ - (Cl- + HCO3- ) • Normal anion gap is 6 – 12 • The difference in “+” & “–” is due to negative charges on albuming • Elevated gaps means increased acids (negatively changed) present MTB S2CK  ‐ p. 336 23 Non‐anion gap metabolic acidosis  • What causes NAGMA? – RTA – Diarrhea • Why is the gap normal in these? – They have elevated Cl (hyperchloremic y ( yp metabolic acidosis) • The anion gap increases from ingested substances (e.g., ethylene glycol or methanol), or organic acids (e.g., lactate) that are anionic and drives chloride levels down MTB S2CK  ‐ p. 336‐337 Renal Tubular Acidosis (RTA)  Distal RTA (Type I) • Pathology in distal tubule • Inability to generate enough bicarbonate – Inadequate bicarb acid cannot be excreted – pH of urine is high, pH of blood is lowp g , p • Caused by factors damaging distal tubule – Amphotericin – SLE or Sjögren syndrome MTB S2CK  ‐ p. 337 Renal Tubular Acidosis Distal RTA (Type I) • Symptoms to look out for? – Calcium oxalate kidney stones – Due to alkaline urine MTB S2CK  ‐ p. 337 Distal RTA calcifies kidney parenchyma (nephrocalcinosis) No acid into the tubule makes the urine basic Distal RTA (Type I)/Diagnostic Tests • Best initial test – Urine pH (> 5.5) • Most accurate test – Infuse ammonium chloride (acid) – Normal person  excretes acid  urine pH ddecreases – Distal RTA  cannot excrete acid  urine pH remains high • Treatment – Replace HCO3 MTB S2CK  ‐ p. 337 Renal Tubular Acidosis Proximal RTA (Type II) • Pathology in proximal tubule • Inability to absorb filtered bicarb • Caused by factors damaging proximal tubule: – AmyloidosisAmyloidosis – Myeloma – Fanconi syndrome – Acetazolamide – Heavy metals MTB S2CK  ‐ p. 337 RTA Type II/Diagnostic Tests Proximal RTA (Type II) • Urine pH: Low (< 5.5) – Because distal tubule absorbs bicarb normally – If you give bicarb: urine pH increases • Osteomalacia – Chronic metabolic acidosis leaches calcium out of the bones and become soft MTB S2CK  ‐ p. 337 24 RTA Type II/Treatment Treatment: • MASSIVE doses of bicarbonate –Because proximal tubule doesn’t absorb it normally • Thiazide diuretics• Thiazide diuretics –Cause volume depletion  ↑ bicarb reabsorption MTB S2CK  ‐ p. 338 Both proximal and distal RTA are hypokalemic. Potassium is lost in the urine. RTA Type IV/Definition/Diagnostic Tests Hyporeninemic, Hypoaldosteronism (Type IV RTA) • Pathology in distal nephron • Problem is decreased amount or effect of aldosterone – Loss of Na+, retention of K+ and H+ • Caused by diabetes • Best test – High urine Na even after Na-restricted diet • Hyperkalemia MTB S2CK  ‐ p. 338 Treatment: • Fludrocortisone –To promote Na+ reabsorption, K+ and H+ secretion RTA Type IV/Treatment MTB S2CK  ‐ p. 338 Fludrocortisone is the steroid with the highest mineralocorticoid or “aldosterone-like” effect. Types of Renal Tubular Acidosis (RTA) Proximal (Type II) Distal (Type I) Type IV Urine pH Blood potassium  level Variable Low  High > 5.5 Low 12): – The anion gap is increased if there are unmeasured anions driving bicarbonateunmeasured anions driving bicarbonate level down MTB S2CK  ‐ p. 339 Respiratory alkalosis from hyperventilation compensates for all forms of metabolic acidosis. 25 Causes of Metabolic Acidosis with  an Increased Anion Gap Cause  Test  Treatment  Lactate Ketoacids Hypotension or  hypoperfusion DKA, starvation Blood lactate  level Acetone level Correct  hypoperfusion Insulin & fluids MTB S2CK  ‐ p. 339 Oxalic acid Ethylene glycol  overdose Crystals on UA Fomepizole,  dialysis Causes of Metabolic Acidosis with  an Increased Anion Gap Cause  Test  Treatment  Formic acid Uremia  Methanol  overdose Renal failure Inflamed retina BUN, creatinine Fomepizole,  dialysis Dialysis  MTB S2CK  ‐ p. 339 Salicylates  Aspirin overdose Aspirin level Alkalinize urine Metabolic Acidosis Arterial Blood Gas in Metabolic Acidosis • The arterial blood gas (ABG) in metabolic acidosis will always have: – Decreased pH < 7.4 – Decreased pCO2 indicating respiratory alkalosis as compensationp – Decreased bicarbonate You cannot determine the etiology of metabolic acidosis from the ABG. MTB S2CK  ‐ p. 339 Metabolic problems always show compensation. Metabolic Alkalosis Key laboratory finding? • Elevated serum bicarbonate level Respiratory compensation? • Decreased respiratory rate  CO2 retention  respiratory acidosis Etiology • GI loss: vomiting or nasogastric suction • ↑ aldosterone: primary, Cushing, ↑ ACTH, volume contraction, licorice • Diuretics • Milk-alkali syndrome • Hypokalemia MTB S2CK  ‐ p. 339‐340 Metabolic Alkalosis/Etiology Arterial Blood Gas in Metabolic Alkalosis • The ABG in metabolic alkalosis will always have: – Increased pH > 7.40 – Increased pCO2 (compensatory respiratory acidosis) – Increased bicarbonate MTB S2CK  ‐ p. 340 Metabolic derangements kill patients with cardiac arrhythmia. They also alter potassium levels. Respiratory Acidosis and Alkalosis • Minute ventilation is a more precise measure of respiratory status than respiratory rate • Minute ventilation = RR x TV MTB S2CK  ‐ p. 340 Hyperventilation may occur with a tiny tidal volume.This does not increase minute ventilation. 26 Causes of Respiratory Acidosis and Alkalosis Respiratory alkalosis Respiratory acidosis Decreased pCO2 Increased minute ventilation Metabolic acidosis as  Compensation Increased pCO2 Decreased minute ventilation Metabolic alkalosis as  Compensation MTB S2CK  ‐ p. 340 • Anemia  • Anxiety  • Pain  • Fever  • Interstitial lung disease • Pulmonary emboli • COPD/emphysema • Drowning  • Opiate overdose • α 1‐antitrypsin deficiency • Kyphoscoliosis • Sleep apnea/morbid obesity Nephrolithiasis Etiology Treatment Long‐term Management Metabolic Acidosis and Stone Formation Nephrolithiasis/Pearls • Most common stone? –Calcium oxalate • Forms more frequently in? –Alkaline urine M t i k f t ?• Most common risk factor? –Overexcretion of calcium in urine MTB S2CK  ‐ p. 340 46-year-old man comes to the ED with excruciating left flank pain radiating to groin. He has some blood in urine. What is the next step? a. Ketorolaca. Ketorolac b. X-ray c. Sonography d. Urinalysis e. Serum calcium level MTB S2CK  ‐ p. 341  Provide pain relief before diagnostic tests What is the most accurate diagnostic test for nephrolithiasis? a. CT scan b. X-ray c. Sonography d. Urinalysis  Less accurate 10-20% false negative. Misses uric acid stones May show hematuria, not specific to causey e. Intravenous pyelogram MTB S2CK  ‐ p. 341 ay s o e a u a, o spec c o cause Requires contrast, takes hours Uric acid stones are not detectable on X-ray, but visualized on CT. Nephrolithiasis/Treatment The best initial therapy for acute renal colic is with: • Analgesics • Hydration I i  CT t t• Imaging  CT noncontrast MTB S2CK  ‐ p. 341 Cystine stones are managed with surgical removal, alkalinizing urine. 27 Nephrolithiasis/Treatment Etiology of the stone determined with: • Stone analysis • Serum calcium, sodium, uric acid, PTH, magnesium, and phosphate levels 24 h i f l l i• 24-hour urine for volume, calcium, oxalate, citrate, cystine, pH, uric acid, phosphate, and magnesium MTB S2CK  ‐ p. 341 Fat malabsorption increases stone formation. Woman with her first episode of renal colic has a 1.8 cm stone in the left renal pelvis. No obstruction. Normal BUN and creatinine. What is the next step in management? a Wait for it to pass; hydrate and observe If < 5mma. Wait for it to pass; hydrate and observe b. Lithotripsy c. Surgical removal d. Hydrochlorothiazide e. Stent placement MTB S2CK  ‐ p. 342  If 5mm If > 2cm Decreases calcium in urine Only releives hydronephrosis Nephrolithiasis • 50% with kidney stones will recur over the next 5 years UTI gives struvite stones MTB S2CK  ‐ p. 342 (magnesium/ammonium/pho sphate). Remove them surgically. A man with a calcium oxalate stone is managed with lithotripsy. Stone is destroyed and passes. Urinary calcium level is increased. Besides increasing hydration, which is most likely to benefit this patient? a. Calcium restriction Can ↑ rate of oxalate stonesb. Hydrochlorothiazide c. Furosemide d. Stent placement e. Increased dietary oxalate MTB S2CK  ‐ p. 342  Increases urinary calcium Only relieves obstruction Can ↑ rate of oxalate stones Nephrolithiasis • Metabolic acidosis removes calcium from bones and increases stone formation • In addition, metabolic acidosis decreases citrate levelsdecreases citrate levels –Citrate binds calcium, making it unavailable for stone formation MTB S2CK  ‐ p. 342 Urinary Incontinence Stress incontinence Urge incontinence Symptoms Older woman with  painless leakage with  coughing, laughing, or  lifting heavy objects Sudden pain in bladder  followed immediately by  the overwhelming urge  to urinate MTB S2CK  ‐ p. 343 Test Have patient stand  and cough; observe  for leakage Pressure measurement  in half‐full bladder;  manometry 28 Urinary Incontinence Stress incontinence Urge incontinence Treatment  1. Kegel exercises 2. Local estrogen  cream 1. Bladder training  exercises 2. Local anticholinergic therapy 1. Oxybutynin MTB S2CK  ‐ p. 343 3. Surgical  tightening of  urethra y y 2. Tolterodine 3. Solifenacin 4. Dariferancin 3. Surgical tightening of  urethra Hypertension Definition Etiologygy Presentation Diagnostic Tests Treatment Hypertensive Crisis Hypertension/Definition • Systolic pressure > 140 mmHg • Diastolic pressure > 90 mmHg • Special population with lower threshold? –Diabetics • Definition of hypertension? – > 130/80 MTB S2CK  ‐ p. 343 Hypertension/Etiology • Most common etiology? (95%) – “Essential hypertension” • Common secondary causes? – Renal artery stenosis – Glomerulonephritis – Coarctation of aortaCoarctation of aorta – Acromegaly – Pheochromocytoma – Hyperaldosteronism – Cushing syndrome or any cause of hypercortisolism including therapeutic use of glucocorticoids – Congenital adrenal hyperplasia MTB S2CK  ‐ p. 343‐344 Hypertension/Presentation • Typically asymptomatic • Symptoms of end organ damage: –Coronary artery disease –Cerebrovascular disease CHF–CHF –Visual disturbance –Renal insufficiency –Peripheral artery disease MTB S2CK  ‐ p. 344 Hypertension/Presentation • Presentation of Secondary Hypertension • Renal artery stenosis: – Bruit is auscultated at flank and is continuous throughout systole and diastole • Glomerulonephritisp • Coarctation of aorta: – Upper extremity > lower extremity BP MTB S2CK  ‐ p. 344 29 Hypertension/Presentation • Acromegaly • Pheochromocytoma: Episodic hypertension with flushing • Hyperaldosteronism: Weakness from hypokalemiahypokalemia MTB S2CK  ‐ p. 344 Hypertension/Diagnostic Tests Other tests to perform in hypertensive patients • EKG • Urinalysis Gl t t l d• Glucose measurements to exclude concomitant diabetes • Cholesterol screening MTB S2CK  ‐ p. 344 Hypertension/Treatment • Best initial therapy? • Lifestyle modifications: – Weight loss (*most effective*) – Sodium restriction – Dietary modification– Dietary modification – Exercise – Tobacco cessation MTB S2CK  ‐ p. 344‐345 Lifestyle modifications are tried for 3 to 6 months before medications are started. Hypertension/Drug Therapy • Best first drug? (all-comers) –Hydrochlorothiazide • If BP > 160/100? –Defines Stage 2 HTN –Start 2 medications immediately MTB S2CK  ‐ p. 345 Hypertension If diuretics don’t control BP, the most appropriate next step in management is: • ACE inhibitor • Angiotensin receptor blocker (ARB) • Beta blocker (BB)• Beta blocker (BB) • Calcium-channel blocker (CCB) MTB S2CK  ‐ p. 345 Hypertension Medications for refractory hypertension: • Central-acting alpha agonists –Alpha methyldopa, clonidine • Peripheral-acting alpha antagonists –Prazosin, terazosin, doxazosin • Direct-acting vasodilators –Hydralazine, minoxidil MTB S2CK  ‐ p. 345 30 Hypertension/Compelling Indications If this is in the history… This is the best initial therapy… Coronary artery disease Diabetes mellitus Benign prostatic  BB, ACE, ARB ACE, ARB Alpha blockers MTB S2CK  ‐ p. 345 hypertrophy Depression and asthma Hyperthyroidism  Osteoporosis  Avoid BBs BB first Thiazides Hypertensive Crisis Defined as HTN with SYMPTOMS • Confusion • Blurry vision • Dyspnea Ch t i• Chest pain MTB S2CK  ‐ p. 345‐346 Hypertensive Crisis • The best initial therapy? –Labetolol or nitroprusside • 2nd line agents? –Enalapril –CCBs: • Diltiazem • Verapamil –Esmolol MTB S2CK  ‐ p. 346 1 Neurology Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Stroke Definition Etiology Presentation Diagnostic Tests Treatment Stroke/Definition • Sudden onset neurological deficit • Death of brain tissue • 3rd most common cause of death in the USA Ri k f t• Risk factors – Hypertension – Diabetes – Hyperlipidemia – Tobacco MTB S2CK  ‐ p. 273 Stroke/Etiology Bleeding (15%) Blockage of flow (85%) • Thrombosis • Embolus H t–Heart • Atrial fibrillation • Valvular heart disease • DVT via Patent foramen ovale –Carotid stenosis MTB S2CK  ‐ p. 273 Stroke/Presentation MTB S2CK  ‐ p. 273 Source: commons.wikimedia.org Stroke/Presentation Middle cerebral artery (MCA) • >90% of all strokes • Weakness or sensory loss – Opposite (contralateral) side from stroke • Contralateral homonymous hemianopsiaContralateral homonymous hemianopsia – Eyes “look toward the side of lesion” • Aphasia – If stroke on same side as speech center – On left in 90% MTB S2CK  ‐ p. 273 2 Stroke/Presentation Anterior cerebral artery (ACA) • Personality/cognitive defects (e.g., confusion) • Urinary incontinence • Leg > arm weakness Posterior cerebral artery (PCA)y ( ) • Loss of consciousness • Ipsilateral (same side) sensory loss of face, 9th, and 10th CN’s • Contralateral sensory loss of limbs • Limb ataxia MTB S2CK  ‐ p. 274 Stroke/Diagnostic Tests Best initial test for stroke is... • CT scan of the head With or without contrast?... • Without contrast Most accurate test for stroke is... • MRI MTB S2CK  ‐ p. 274 Stroke/Diagnostic Tests CT • Done first • Excludes hemorrhage • Prior to treatment MTB S2CK  ‐ p. 274 Source: Mohammad Maruf, MD Stroke/Treatment Nonhemorrhagic • Best initial therapy when LESS than 3 hours since onset... – Thrombolytics • More than 3 hours since onset... – AspirinAspirin • If the patient is already on aspirin... – ADD dipyridamole OR – SWITCH to clopidogrel MTB S2CK  ‐ p. 274 – 275 Stroke/Treatment Hemorrhagic • Best initial treatment... – Nothing MTB S2CK  ‐ p. 275 Stroke/Evaluation of Causes & Treatment Echocardiogram • Damaged valves? –Surgical replacement • Thrombi? –Heparin followed by warfarin to INR of 2-3 MTB S2CK  ‐ p. 275 3 Stroke/Evaluation of Causes & Treatment Source: Kjetil Lenes Stroke/Evaluation of Causes & Treatment Electrocardiogram • Atrial fibrillation or atrial flutter – Warfarin as long as arrhythmia persists no P wave Source: J Heuser P wave NSR A‐fib Stroke/Evaluation of Causes & Treatment Holter monitor • Detect arrhythmias • If initial EKG is normal: Do Holter monitor • Detect atrial arrhythmias G t iti it th EKG• Greater sensitivity than EKG MTB S2CK  ‐ p. 275 Stroke/Evaluation of Causes & Treatment Holter monitor Source: Macro987 Stroke/Evaluation of Causes & Treatment Carotid duplex ultrasound • Carotid stenosis is a frequent cause of emboli • Surgery? S t ti d 70% t i–Symptomatic and >70% stenosis –Endarterectomy superior to carotid angioplasty MTB S2CK  ‐ p. 275 Stroke Patient presents with: • Sudden onset unilateral weakness • Facial droop • +/- Speech deficits Best Initial Test: Head CT without contrast No acute process Acute hemorrhage Likely ischemic stroke Likely hemorrhagic stroke 4 Stroke  Treatment: < 3 hours from onset of symptoms Likely ischemic stroke > 3 hours from onset of symptoms Symptoms last < 24 hours, then resolve Treatment: Transient MTB S2CK  ‐ p. 274 – 275  Treatment: • Consider TPA, if no hx of bleeding Treatment: • Aspirin • ADD dipyridamole or switch to clopidogrel if already on aspirin Transient ischemic attack Perform further studies to asses etiology Stroke Treatment: Control blood pressure • Optimal systolic BP is between 140-160 mmHg • If > 170 mmHg use nicardipine enalaprilat or labetalol Likely hemorrhagic stroke • If > 170 mmHg, use nicardipine, enalaprilat, or labetalol Reverse anticoagulation • If patient is on warfarin  fresh frozen plasma, vitamin K • If patient is on heparin  protamine sulfate Stroke Goals! • Diabetes – Hemoglobin A1C 5 Headache/Migraine • Visual disturbance • Photophobia “aura” May be related to: • Food/menses • Precipitated by emotions Ph i lPhysical exam • Rare cases: aphasia, numbness, dysarthria, weakness Diagnostic tests • All normal • Scan head the first time, then stop MTB S2CK  ‐ p. 276 Headache/Migraine Treatment • Abortive – Triptans or ergotamine • Prophylactic (preventive) – > 3 migraines/month Propranolol– Propranolol Other preventive medications: • Calcium-channel blockers • Tricyclic antidepressants • SSRIs • Botulinum toxin injections MTB S2CK  ‐ p. 277 Headache/Cluster Headache Symptoms • Frequent, short duration, high intensity • Men 10X MORE than women!!! Physical examination • Red, tearing eye with rhinorrhea, g y • Horner syndrome occasionally Diagnostic tests • Scan head first time • No need for subsequent imaging with recurrences MTB S2CK  ‐ p. 276 Headache/Cluster Headache Treatment • Abortive – Triptans – Ergotamine – 100% oxygen100% oxygen • Preventive – Verapamil – Lithium – Prednisone MTB S2CK  ‐ p. 277 Headache/Giant Cell (Temporal) Arteritis Symptoms • Visual disturbance, jaw claudication • Muscle pain, fatigue, and weakness Physical exam • Visual loss, temporal area tenderness Diagnostic tests • Elevated ESR • Most accurate test?  Biopsy! Treatment • Prednisone MTB S2CK  ‐ p. 276 • Episodic pain • Unilateral periorbital intense pain • Lacrimation • Eye-reddening • Nasal stuffiness • Lid ptosis Headache Tension H d h • Bilateral “band-like” pressure • Lasts 4-6 hours • Normal P/E Headache • +/- Aura, photophobia • Related to food/emotions/menses • Rare: aphasia, numbness, dysarthria Cluster Migraine MTB S2CK  ‐ p. 389.4 Headache Treatment • NSAIDs • Acetaminophen Cluster Headache Acute Treatment • Sumitriptan • Octreotide • Oxygen Prophylaxis • Propranolol • Sodium valproate Treatment • Avoid triggers • NSAIDs • 5-HT1 agonists 3 attacks/month Prophylaxis • Verapamil • Prednisone • Sodium valproate 6 Headache/Pseudotumor Cerebri Associated with… • Obesity • Oral contraceptives • Vitamin A toxicity • Mimics brain tumor: nausea & vomiting Physical exam • Papilledema • Diplopia: 6th CN (abducens) palsy MTB S2CK  ‐ p. 276 Cranial Nerve 6 Palsy  Headache/Pseudotumor Cerebri Diagnostic tests • CT or MRI –Normal –Done to exclude intracranial mass • Lumbar puncture –Increased pressure • CSF –Normal MTB S2CK  ‐ p. 277 Headache/Pseudotumor Cerebri Treatment • Acetazolamide +/- furosemide • Weight loss • Steroids • Repeated lumbar puncture • Ventriculoperitoneal shunt MTB S2CK  ‐ p. 277 Headache/Trigeminal Neuralgia • Idiopathic • 5th CN • Severe, overwhelming “knife-like” facial pain Precipitated by… • ChewingChewing • Touching the face • Pronouncing words in which the tongue strikes the back of front teeth • No specific diagnostic test MTB S2CK  ‐ p. 278 Headache/Trigeminal Neuralgia Treatment • Carbamazepine or oxcarbazepine • Baclofen • Lamotrigine • Surgical decompression when failing medications MTB S2CK  ‐ p. 278 7 Headache/Postherpetic Neuralgia • Residual pain following resolution of herpes zoster (shingles) vesicular lesions Shi l i i f l• Shingles is a painful dermatomal rash that occurs in 15% with prior varicella zoster (chickenpox) infection MTB S2CK  ‐ p. 278 Shingles rash caused by herpes zoster virus. Source: NIAID Headache/Postherpetic Neuralgia Acute Treatment: • Acyclovir, famciclovir, or valacyclovir reduce the incidence of pain • Steroids do not help MTB S2CK  ‐ p. 278 Headache/Postherpetic Neuralgia Treatment • Tricyclic antidepressants (amitriptyline) • Gabapentin or pregabalin • Carbamazepine • Phenytoin • Topical capsaicin • Antiepileptic medications – Have some beneficial effect in neuropathic pain (e.g., postherpetic neuralgia or peripheral neuropathy) • None work in > 50% to 70% MTB S2CK  ‐ p. 278 Prevention of Herpes Zoster (Shingles) Zoster vaccine • Everyone > 60 • High dose varicella vaccine • Decreases reactivation of varicella into tzoster MTB S2CK  ‐ p. 278 Seizures Classification Diagnostic Tests Treatment Management Classification of Seizures • Partial • Absence (petit mal) • Generalized (tonic-clonic) • Status epilepticusS a us ep ep cus MTB S2CK  ‐ p. 279 8 Partial Seizures Focal to one part of the body –Limited to arm or leg Partial seizures can be: •“Simple” –Intact consciousness •“Complex” –Loss of consciousness MTB S2CK  ‐ p. 279 Absence Seizures • Also referred to as petit mal • Consciousness briefly impaired • Patient often remains upright and often appears normal or stares into space Ab i ft i• Absence seizures occur more often in children MTB S2CK  ‐ p. 280 Generalized Seizures • Also referred to as tonic-clonic • Generalized seizure Varying phases • Muscular rigidity (tonic) • Followed by jerking of muscles for several minutes (clonic) MTB S2CK  ‐ p. 280 Generalized Seizures/Causes  • Hyponatremia or hypernatremia • Hypoxia • Hypoglycemia • Any CNS infection –Encephalitis, meningitis, abscess • Any CNS anatomic abnormality –Trauma, stroke, tumor MTB S2CK  ‐ p. 278 Generalized Seizures/Causes  • Hypocalcemia • Uremia (elevated creatinine) • Hepatic failure • Withdrawal –Alcohol, barbiturate, and benzodiazepine • Cocaine toxicity • Hypomagnesemia (rare) MTB S2CK  ‐ p. 278 Seizures/Diagnostic Tests Electroencephalogram (EEG) • The right answer after the other tests are done • If CT or MRI are normal N i t i EEG if th i l• No point in EEG if there is a clear metabolic, toxic, or anatomic defect causing the seizure MTB S2CK  ‐ p. 279 9 Delerium, Stupor, and Coma • Altered consciousness • Unresponsiveness to stimuli • From metabolic, toxic, and CNS infections Also called… • Confusion “Diffi lt ith l”• “Difficulty with arousal” • “Obtundation” • When severe enough, a seizure occurs • Confusion is to coma and seizure, as angina is to myocardial infarction MTB S2CK  ‐ p. 279 Treatment of Status Epilepticus The only seizure treatment that is clear Best initial therapy... • Benzodiazepine –Lorazepam –Diazepam intravenously MTB S2CK  ‐ p. 279 Treatment of Status Epilepticus If seizure persists... Phenytoin or fosphenytoin • Fosphenytoin = phenytoin efficacy • Fosphenytoin has fewer adverse effects Ph t iPhenytoin • Hypotension and AV block Fosphenytoin • No BP or cardiac effect • Can be given more rapidly MTB S2CK  ‐ p. 279 Treatment of Status Epilepticus 1. Benzodiazepines did NOT work 2. Fosphenytoin did NOT work 3. Use phenobarbital MTB S2CK  ‐ p. 279 Treatment of Status Epilepticus What if barbiturates do NOT work? 1.Neuromuscular blocking agents allow intubation: – Succinylcholine – Vecuronium – Pancuronium 2. General anesthesia – Midazolam or propofol – Place on ventilator before propofol, which can stop breathing MTB S2CK  ‐ p. 278 Treatment of Status Epilepticus To summarize... 1. Benzodiazepine 2. Fosphenytoin 3. Phenobarbital 4. General anesthesia MTB S2CK  ‐ p. 280 10 Epilepsy Treatment/Indications Antiepileptic drugs • Not long term for single seizure • When should you start after a single seizure? P t ti i t t il ti–Presentation in status epilepticus –Abnormal EEG –Family history of seizures MTB S2CK  ‐ p. 280 Choice of Antiepileptic Drugs • Status epilepticus treatment is clear • Epilepsy long-term treatment is not clear • No medication is clearly superior to the others • Phenytoin, valproic acid, and carbamazepine all have nearly equal efficacy • Gabapentin topiramate lamotrigine• Gabapentin, topiramate, lamotrigine, oxcarbazepine, or levetiracetam • Ethosuximide is the best therapy for absence seizures • You cannot be asked to choose between them based on efficacy MTB S2CK  ‐ p. 280 Choice of Antiepileptic Drugs • If not controlled with single agent, an alternate medication should be tried • If still not controlled, add a second drug • If multiple medications do not work: Surgery!Surgery! MTB S2CK  ‐ p. 280 Discontinuance of Antiepileptic Medication • Wait until seizure-free for 2 years Sleep deprivation EEG: • The best way to detect possibility of recurrencerecurrence • Elicits abnormal activity with more sensitivity • This is NOT a 100% sensitive test! MTB S2CK  ‐ p. 281 38-year-old man evaluated for seizures achieves partial control with second medication. He drives to work daily. What do you do about his ability to drive? a. Confiscate his license b. Allow him to drive if he is seizure-free for 1 year c. Allow him to drive as long as his seizure history is t d hi li Rules vary state to state Cannot prevent noted on his license d. Recommend that he find an alternate means of transportation e. Do not let him leave the office unless he is picked up by someone; no further driving f. Allow him to drive as long as he is accompanied MTB S2CK  ‐ p. 281  Rules vary state to state Cannot “incarcerate” Being accompanied does not prevent seizures Subarachnoid  Hemorrhage Definition/EtiologyDefinition/Etiology Diagnostic Tests Treatment 11 Subarachnoid Hemorrhage • Rupture of aneurysm • Usually in Circle of Willis (anterior) • Aneurysms found in 2% of autopsies • Majority never rupture • Cause of rupture not clear MTB S2CK  ‐ p. 281 Circle of Willis MTB S2CK  ‐ p. 281 Subarachnoid Hemorrhage/Diagnosis “What is the most likely diagnosis?” • Look for... – Sudden onset of severe headache with meningeal irritation (stiff neck, photophobia) – and fever! • Loss of consciousness in 50% • Sudden increase in intracranial pressure • Focal neurological complications occur in 30% MTB S2CK  ‐ p. 281 Subarachnoid Hemorrhage/Diagnosis How does SAH differs from meningitis? • Very sudden in onset • Loss of consciousness MTB S2CK  ‐ p. 281 Subarachnoid Hemorrhage/Diagnosis Best initial test is... • CT without contrast (95% sensitive) Most accurate test is... • Lumbar puncture showing bloodshowing blood MTB S2CK  ‐ p. 282 Source: Saba Ansari, MD Subarachnoid Hemorrhage/Diagnosis • LP necessary only for 5% with falsely negative CT • CSF in SAH has both increased WBCs and RBCs • WBC can mimic meningitis • Ratio of WBCs to RBCs will be normal in SAH MTB S2CK  ‐ p. 282 12 Subarachnoid Hemorrhage/Diagnosis WBC count > normal 1:500? – Suspect meningitis Xanthochromia • Yellow CSF • From breakdown red cells in CSF EKG • May show large or inverted T waves • Suggestive of myocardial ischemia • “Cerebral T waves” • From “excessive sympathetic activity” MTB S2CK  ‐ p. 282 Subarachnoid Hemorrhage/Diagnosis Angiography • Determines site of aneurysm • Guides lesion repair • MRA Diagnosis based on... • CT and sometimes LP • Only angiography can tell location MTB S2CK  ‐ p. 282 Subarachnoid Hemorrhage/Diagnosis MTB S2CK  ‐ p. 282 Subarachnoid Hemorrhage/Treatment • Nothing reverses hemorrhage • Nimodipine (calcium-channel blocker) prevents subsequent ischemic stroke MTB S2CK  ‐ p. 283 Subarachnoid Hemorrhage/Treatment Embolization (coiling) • Catheter “clogs up” site of bleeding • Prevents repeated hemorrhage • Interventional neuroradiologist places platinum wire p • Embolization superior to surgical clipping for survival and complications MTB S2CK  ‐ p. 283 Subarachnoid Hemorrhage/Treatment Ventriculoperitoneal shunt • SAH associated with hydrocephalus • Shunt only if hydrocephalus develops MTB S2CK  ‐ p. 283 13 Subarachnoid Hemorrhage/Treatment Seizure prophylaxis • Phenytoin is not routine • If the question asks “Which of the following is most likely to decrease mortality?”mortality? ... –Phenytoin is not the answer MTB S2CK  ‐ p. 283 “Consultation” is only right when you want to do a procedure that isn’t given as a choice. Subarachnoid Hemorrhage/Treatment MTB S2CK  ‐ p. 284 A woman in the ED with a severe headache one day prior to admission. Temp 103°F, nuchal rigidity & photophobia. Head CT is normal. LP CSF WBCs: 1,250 RBCs: 50,000 What’s the next step? a. Angiography 50 000 RBC h ld lFor location of SAH, this is not SAHg g p yb. Ceftriaxone and vancomycin c. Nimodipine d. Embolization e. Surgical clipping f. Repeat CT scan with contrast g. Neurosurgical consultation MTB S2CK  ‐ p. 283  50,000 RBC should only give 50-100 WBCs 1,250 WBCs is infection Prevent SAH stroke Permanent SAH fix Worse alternative to embolization Useless for blood Don’t consult unless you REALLY want a procedure not listed Spine Disorders Anterior Spinal Artery Infarction Subacute Combined Degeneration of the Cord Spinal Trauma Brown‐Séquard Syndrome Syringomyelia Anterior Spinal Artery Infarction • Loss of all function except posterior column • Position and vibratory sensation intact • Flaccid paralysis below the level of infarction • Loss of deep tendon reflexes (DTRs) at level of infarction • Evolves into spastic paraplegia several weeks later MTB S2CK  ‐ p. 284 • Evolves into spastic paraplegia several weeks later • Loss of pain and temperature • Extensor plantar response No specific therapy Subacute Combined Degeneration  of the Cord • B12 deficiency or neurosyphilis • Position & vibratory sensation lost • Everything else intact MTB S2CK  ‐ p. 284 14 Spinal Trauma • Acute limb weakness and/or sensory disturbance • Below level of injury • Severity in proportion to degree of injury • Sphincter function impairedp p • Loss of DTRs at level of injury • Followed by hyperreflexia below level of trauma • Treat with glucocorticoids MTB S2CK  ‐ p. 284 Brown‐Séquard Syndrome • Unilateral hemisection of spinal cord • Due to injury – Knife cutting half the cord • On physical exam... Ipsilateral Contralateral • No treatment MTB S2CK  ‐ p. 284 Ipsilateral Contralateral • Motor • Position • Vibration • Pain • Temperature Syringomyelia • Fluid-filled, dilated central canal of spinal cord • Widening “bubble” or cavitation damages neural fibers passing near center of spine • Caused by tumor or severe trauma to spine MTB S2CK  ‐ p. 285 Syringomyelia “What is the most likely diagnosis?” Look for: • Loss of pain & temperature bilaterally • Across the upper back and both arms • Look for the phrase “capelike distribution” MTB S2CK  ‐ p. 285 Look for the phrase capelike distribution • Loss of reflexes • Muscle atrophy Syringomyelia The most accurate test is... • MRI The best treatment is... • Surgical • Removal of tumor • Drain cavity MTB S2CK  ‐ p. 285 Source: Mohammad Maruf, MD. CNS Abscess & Disease Brain abscess Neurocutaneous diseases 15 Brain Abscess/Definition & Etiology • Collection of infected material in brain parenchyma • Acts as space-occupying lesion • Spreads from contiguous infection • Starts in sinuses, mastoid air cells, or otitis , , media • Any bacteremia – Pneumonia and endocarditis cause bacteremia, which can lead to a brain abscess MTB S2CK  ‐ p. 285 Brain Abscess/Presentation • Headache, nausea, vomiting, fever, seizures, and focal neurological findings • No way to distinguish brain abscess from cancer without a biopsy • Cancer gives fever too• Cancer gives fever, too MTB S2CK  ‐ p. 286 Brain Abscess/Diagnostic Tests “Best initial test is... • Head CT or MRI “Most accurate test is... • Brain biopsy MTB S2CK  ‐ p. 286 Source: Nishith Patel Brain Abscess/Diagnostic Tests • Scan shows a “ring” or contrast-enhancing lesion • Surrounding edema • Mass effect • Cancer and infectionCancer and infection are indistinguishable based on imaging study alone MTB S2CK  ‐ p. 286 Source: Nishith Patel Brain Abscess/Microbiology Biopsy is essential • Only biopsy distinguishes abscess from cancer • Only way to know sensitivity of organism Abscesses can be... • Staphylococci, streptococci, Gram-negative bacilli, and anaerobes MTB S2CK  ‐ p. 286 and anaerobes • Frequently mixed (polymicrobial) Treat for... • 6 to 8 weeks intravenously • Followed by 2 to 3 more months orally Brain Abscess/Treatment Empiric therapy • Penicillin + metronidazole + ceftriaxone (or cefepime) • Vancomycin (alternative to penicillin) • Use vancomycin if there’s been recent neurosurgeryneurosurgery MTB S2CK  ‐ p. 287 16 Neurocutaneous Diseases • Tuberous sclerosis • Neurofibromatosis (von Recklinghausen Disease) • Sturge-Weber Syndrome MTB S2CK  ‐ p. 287 Tuberous Sclerosis • Neurological abnormalities – Seizures, slowly progressive mental deterioration • Skin – Adenoma sebaceum (reddened facial nodules) – Shagreen patches (leathery plaques on trunk) – Ash leaf (hypopigmented) patchesAsh leaf (hypopigmented) patches • Retinal lesions • Cardiac rhabdomyomas • No specific treatment • Control seizures MTB S2CK  ‐ p. 287 Neurofibromatosis  (von Recklinghausen Disease) • Neurofibromas: soft, flesh-colored lesions attached to peripheral nerves • 8th CN tumors • Cutaneous hyperpigmented lesions (café au lait spots) • Meningioma and gliomas MTB S2CK  ‐ p. 287 Source: Mohammad Maruf, MD. Neurofibromatosis  (von Recklinghausen Disease) • No specific treatment • Lesions affecting 8th CN may require surgical decompression to preserve hearing MTB S2CK  ‐ p. 287 Sturge‐Weber Syndrome • Port-wine stain of face • Seizures • CNS – Homonymous hemianopsia – Hemiparesis – Mental subnormality • Skull X-ray – Calcification of angiomas • No treatment • Control seizures MTB S2CK  ‐ p. 288 Movement Disorders – Part 1 Essential Tremor Parkinsonism Restless Leg Syndrome Huntington Disease Tourette Disorder Multiple Sclerosis 17 Essential Tremor • Occurs at both rest and intention (i.e., reaching for things) • Tremor greatest in hands, but can affect head • Affects some manual skills – Handwriting or use of computer keyboard • Caffeine makes it worse MTB S2CK  ‐ p. 288 • Caffeine makes it worse • Treat with propranolol • Tremor at rest and exertion improved with a drink of alcohol is key to diagnosis Essential Tremor Parkinsonism/Definition • Loss of substantia nigra • Decrease in dopamine • Movement disorder • Tremor and gait disturbance MTB S2CK  ‐ p. 288 • No test for parkinsonism • Diagnosis is entirely on clinical presentation Parkinsonism/Etiology • Head trauma from boxing • Use of antipsychotic medications – Thorazine • Encephalitis • ReserpineReserpine • Metoclopromide MTB S2CK  ‐ p. 288 Parkinsonism/Presentation Look for 50-60 (or older) with... • Tremor • Muscular rigidity • Bradykinesia (slow movements) • Shuffling gait with unsteadiness on turning T d t f ll MTB S2CK  ‐ p. 289 • Tendency to fall • Cogwheel rigidity (slowing of movement on passive flexion or extension of extremity) • Facial expression limited (hypomimia) • Writing is small (micrographia) Pill Rolling Tremor 18 Parkinson Facies  Parkinsonism/Presentation • Postural instability or orthostatic hypotension • Inability of pulse and BP to reset • Lightheadedness when getting up from seated position • The most frequent Parkinsonism question is: Treatment • Know the drugs! MTB S2CK  ‐ p. 289 Parkinsonism/Treatment Mild disease • Anticholinergic medications relieve tremor and rigidity – Benztropine and trihexyphenidyl – Adverse effects • Dry mouth • Worsening prostate hypertrophy • Constipation • More frequent in older patients MTB S2CK  ‐ p. 289 Parkinsonism/Treatment Mild disease • Amantadine – Increases release of dopamine from substantia nigra – Definitely the answer in older patients (> 60) y p ( ) intolerant of anticholinergic medications MTB S2CK  ‐ p. 289 Parkinsonism/Treatment Severe disease • Inability to care for themselves, orthostatic • Dopamine agonists – Pramipexole – RopiniroleRopinirole – Bromocriptine and cabergoline are older agents – Infrequent use because of adverse effects MTB S2CK  ‐ p. 289 Parkinsonism/Treatment Severe disease • Levodopa/carbidopa – Single most effective medication – Associated with “on/off” phenomena – Episodes of insufficient dopamine (“off”)Episodes of insufficient dopamine ( off ) characterized by bradykinesia – The “on” effect is too much dopamine resulting in dyskinesia MTB S2CK  ‐ p. 289 19 Parkinsonism/Treatment Severe disease • COMT inhibitors (tolcapone, entacapone) – Extends duration of levodopa/carbidopa – Blocks metabolism of dopamine – Used only with levodopa/carbidopa MTB S2CK  ‐ p. 289 Used only with levodopa/carbidopa – Use when there are “on/off” phenomena to even out dopamine level – When response to therapy is inadequate Parkinsonism/Treatment Severe disease • MAO inhibitors (rasagiline, selegiline) – As single agent or an adjunct to levodopa/carbidopa – Block metabolism of dopamine • Deep brain stimulation Electrical stimulation– Electrical stimulation – Highly effective in some patients MTB S2CK  ‐ p. 289 70-year-old man with extremely severe parkinsonism comes to ED with psychosis and confusion developing at home. He’s maintained on levodopa/carbidopa, ropinirole, and tolcapone. What’s the most appropriate next step in management? Don’t stop meds! a. Stop levodopa/carbidopa b. Start clozapine c. Stop ropinirole d. Stop tolcapone e. Start haloperidol MTB S2CK  ‐ p. 290  Don’t stop meds severe parkinsonism Don’t stop meds severe parkinsonism More adverse effects than clozapine Don t stop meds! Severe Parkinsonism Spasticity • Painful, contracted muscles • From damage to CNS • Often associated with MS • No single treatment always effective • Baclofen and tizanadine (central-acting alpha agonist) may work MTB S2CK  ‐ p. 290 Restless Legs Syndrome • Uncomfortable sensation in legs • “Creepy and crawly” at night • Bed partner who is being kicked at night • Discomfort worsened by caffeine • Relieved by moving legs • Treat with dopamine agonists (e.g., pramipexole) MTB S2CK  ‐ p. 290 Huntington Disease (HD) • Hereditary disease • CAG trinucleotide repeat sequences on chromosome 4 MTB S2CK  ‐ p. 291 20 Huntington Disease/Presentation “What is the most likely diagnosis?” HD is the answer when you see... • Choreaform movement disorder (dyskinesia) • Dementia • Behavior changes MTB S2CK  ‐ p. 291 Behavior changes – Irritability, moodiness, antisocial behavior • Onset between 30 - 50 • Often with family history of HD Huntington Disease Diagnosis • Symptom triad –Movement –Memory –Mood • Genetic testing >99% accurate MTB S2CK  ‐ p. 291 Huntington Disease Treatment • No treatment can reverse HD • Dyskinesia treated with tetrabenazine • Psychosis treated with haloperidol or ti i MTB S2CK  ‐ p. 291 quetiapine Tourette Disorder Idiopathic disorder • Vocal tics, grunts, and coprolalia • Motor tics (sniffing, blinking, frowning) • Obsessive-compulsive behavior No specific diagnostic testNo specific diagnostic test Treat with neuroleptics • e.g. Fluphenazine, clonazepam, pimozide ADHD drugs • Methylphenidate MTB S2CK  ‐ p. 291 Multiple Sclerosis • Idiopathic disorder • Exclusively CNS (brain and spinal cord) • More common in white women living in colder climates MTB S2CK  ‐ p. 291 Multiple Sclerosis/Presentation • Most common presentation: “What is the most likely diagnosis?” Look for: • Multiple neurological deficits of CNS • Affects any aspect of CNS presentation: – Blurry vision – Visual disturbance from optic neuritis MTB S2CK  ‐ p. 291 NEUR_02_19 21 Multiple Sclerosis/Presentation • After optic neuritis, the most common abnormalities are motor and sensory • Other findings – Fatigue – Spasticity and hyperreflexia – Cerebellar deficitsCerebellar deficits Least common findings • Cognitive defects • Dementia • Sexual dysfunction MTB S2CK  ‐ p. 292 Multiple Sclerosis/Diagnostic Tests MRI: “Best initial” AND “Most accurate” test MTB S2CK  ‐ p. 292 Source: Saba Ansari, MD Multiple Sclerosis/Diagnostic Tests Lumbar puncture: CSF • Mild elevation in protein • < 50 - 100 WBCs – Oligoclonal bands: Found in 85% of MS – Oligoclonal bands: Not specific to MS • Oligoclonal bands are the answer in 3% - 5% with equivocal (nondiagnostic) MRI MTB S2CK  ‐ p. 292 Multiple Sclerosis/Treatment The “best initial therapy” for acute exacerbations of MS... • High-dose steroids MTB S2CK  ‐ p. 292 Multiple Sclerosis/Treatment Drugs that prevent relapse and progression • Glatiramer (copolymer1) • Beta-interferon • Natalizumab • MitoxantroneMitoxantrone • Fingolimod • Dalfampridine • Azathioprine and cyclophosphamide (rarely used) MTB S2CK  ‐ p. 292 Multiple Sclerosis/Treatment A new MS treatment is started. MRI shows new, multiple white matter hypodense lesions. What is it? • Progressive multifocal MTB S2CK  ‐ p. 293 g leukoencephalopathy (PML) What is the cause? • Natalizumab 22 Movement Disorders – Part 2   Amyotrophic Lateral Sclerosis Charcot‐Marie‐Tooth Disease  Peripheral Neuropathy Facial Nerve Palsy Guillain‐Barré Syndrome Myasthenia Gravis Amyotrophic Lateral Sclerosis (ALS) • Exclusively a loss of upper and lower motor neurons MTB S2CK  ‐ p. 293 • Idiopathic Amyotrophic Lateral Sclerosis (ALS) “What is the most likely diagnosis?” Look for... • Weakness starting in 20s to 40s • Combination of upper and lower motor neuron loss Initial presentation... Diffi lt h i d ll i MTB S2CK  ‐ p. 293 • Difficulty chewing and swallowing • Decrease in gag reflex • Pooling of saliva in pharynx and weak cough • Frequent episodes of aspiration Death in patients within 3 to 5 years after diagnosis • Most commonly due to respiratory failure Presentation of Amyotrophic Lateral Sclerosis Upper Motor Neurons Lower Motor Neurons Weakness  Spasticity Weakness Wasting MTB S2CK  ‐ p. 293 Hyperreflexia Extensor plantar responses Fasciculations Kinetic Tremor Fasciculations 23 Amyotrophic Lateral Sclerosis/Diagnostic Tests Electromyography • Loss of neural innervation in multiple muscle groups • CPK levels  MTB S2CK  ‐ p. 293 Amyotrophic Lateral Sclerosis/Treatment Riluzole • Reduces glutamate buildup in neurons • Delays progression Baclofen • Treats spasticity CPAP d BiPAPCPAP and BiPAP • Help respiratory difficulties secondary to muscle weakness Tracheostomy • Maintenance on ventilator necessary when disease advances MTB S2CK  ‐ p. 293 Charcot‐Marie‐Tooth Disease  • Genetic disorder • Lose both motor and sensory innervation – Distal weakness & sensory loss – Wasting in legs – Decreased DTRs – Tremor MTB S2CK  ‐ p. 294 Tremor • Foot deformity with high arch common (pes cavus) • Legs look like inverted “champagne bottles” • Most accurate test: Electromyography • No treatment Peripheral Neuropathy • MCC: Diabetes mellitus • Other causes: uremia, alcoholism, and paraproteinemias (e.g., MGUS) • “Best initial therapy” – Pregabalin, gabapentin • Tricyclic antidepressants MTB S2CK  ‐ p. 294 • Tricyclic antidepressants • Most seizure medications effective in some people – Phenytoin – Carbamazepine – Lamotrigine Specific Peripheral Nerve Neuropathies Nerve Precipitating event Presentation Wasting of  hypothenar eminence,  4th/5th digit pain Wrist drop Ulnar nerve Radial nerve Biker, pressure on palms of  hands, medial elbow trauma Pressure on inner/upper arm,  MTB S2CK  ‐ p. 294 p Pain/numbness  of outer aspect  of thigh Lateral  cutaneous n.  of the thigh pp use of crutches, “Saturday night  palsy” (falling asleep on arm) Obesity, pregnancy, sitting with  crossed legs Specific Peripheral Nerve Neuropathies Nerve Precipitating event Presentation Tibial nerve Peroneal nerve Worsens with walking High boots, pressure on the  back of knee Pain/numbness in  ankle & sole of foot Weak foot with  decreased  MTB S2CK  ‐ p. 294 Median  nerve Typists, carpenters,  working with hands dorsiflexion and  eversion Thenar eminince,  pain/numbness  in 1st 3 fingers 24 Facial (Seventh Cranial) Nerve Palsy • Also known as Bell’s palsy • Mostly idiopathic • Some identified causes… –Lyme, sarcoidosis, herpes zoster, and tumorstumors • Look for statement “the face feels stiff” or “pulled to one side” MTB S2CK  ‐ p. 294 Facial (Seventh Cranial) Nerve Palsy Paralysis of entire side of face • Stroke paralyzes only lower half of face • Upper half of face innervate from both cerebral hemispheres Difficulty closing eye MTB S2CK  ‐ p. 295 Difficulty closing eye If they can wrinkle forehead on affected side worry about stroke • Cannot wrinkle forehead = Bell's palsy! Facial (Seventh Cranial) Nerve Palsy Hyperacusis • Sounds are extra loud • 7th CN supplies stapedius muscle – Acts as a “shock absorber” on ossicles of middle ear Taste disturbance • 7th CN supplies sensation of taste to anterior two-thirds of tongue MTB S2CK  ‐ p. 295 Facial (Seventh Cranial) Nerve Palsy The most accurate test is... • Electromyography and nerve conduction studies • But...no test is usually done MTB S2CK  ‐ p. 295 Facial (Seventh Cranial) Nerve Palsy The best initial therapy is... • Prednisone • But... –60% of patients have full recovery even without treatmentwithout treatment • Acyclovir does not help MTB S2CK  ‐ p. 278 38-year-old with pain near his ear followed by weakness of one side of his face. Both upper and lower parts of face are weak. Sensation is intact. What is the most common complication? a. Corneal ulceration b. Aspiration pneumonia c. Sinusitis d. Otitis media e. Deafness f. Dental caries MTB S2CK  ‐ p. 295  Cavities do not paralyze your face! Sounds are actually extra loud Gag reflex and cough are normal Nasal discharge & face pain Ear pain, decreased hearing 25 Guillain‐Barré Syndrome • Acute inflammatory polyneuropathy • Autoimmune damage of multiple peripheral nerves No CNS involvement • Circulating antibody attacks myelin sheaths of peripheral nerves MTB S2CK  ‐ p. 296 • Associated with Campylobacter jejuni Guillain‐Barré Syndrome “What is the most likely diagnosis?” Look for: • Weakness of legs that ascends from feet • Moves toward chest • Loss of DTRs S h ild di t b• Some have mild sensory disturbance • Respiratory muscle weakness GBS hits diaphragm! • Autonomic dysfunction with hypotension, HTN, or tachycardia can occur MTB S2CK  ‐ p. 296 Guillain‐Barré Syndrome • CSF = increased protein + normal cell count Most specific diagnostic test • Nerve conduction studies/electromyography – Decrease in propagation of electrical impulses along nervesnerves MTB S2CK  ‐ p. 296 Guillain‐Barré Syndrome Tests of respiratory muscle involvement • Inspiration is the “active” part of breathing and the patient loses the strength to inhale – Decrease in FVC – Decrease in peak inspiratory pressure • PFTs tell who might die from GBS MTB S2CK  ‐ p. 296 Guillain‐Barré Syndrome Treatment • Intravenous immunoglobulin (IVIG) or plasmapheresis are equal in efficacy • Prednisone is a wrong answer for GBS, doesn’t help • Combining IVIG and plasmapheresis is incorrect MTB S2CK  ‐ p. 296 Woman comes with bilateral leg weakness over last few days. No knee jerk or ankle jerk reflexes. Weakness started in feet and progressed up to calves and thighs. Which of the following is the most urgent step? a. Pulmonary function testing b. Arterial blood gas c. Nerve conduction study d. Lumbar puncture e. Peak flow meter MTB S2CK  ‐ p. 296  Don’t wait for inc CO2 on ABG Most accurate, but not next For Dx, not severity assessment Assesses expiratory flow 26 Myasthenia Gravis • Muscular weakness from antibodies against acetylcholine receptors at the NMJ MTB S2CK  ‐ p. 297 Myasthenia Gravis/Presentation “What is the most likely diagnosis?” • Look for... – Double vision and difficulty chewing – Weakness of limb muscles worse at end of the day – Ptosis – Weakness with sustained activityWeakness with sustained activity – Normal pupillary responses • Extraocular muscles & mastication (masseter) are often the only 2 muscular activities universally done by people (e.g., watching TV and eating) MTB S2CK  ‐ p. 297 Myasthenia Gravis/Diagnostic Tests Best initial test is... • Acetylcholine receptor antibodies (80% – 90% sensitive) • Better answer than edrophonium testing • EdrophoniumEdrophonium – Short-acting inhibitor of acetylcholinesterase – Temporary bump up in acetylcholine levels – Associated with a clear improvement in motor function that lasts for a few minutes MTB S2CK  ‐ p. 297 Myasthenia Gravis/Diagnostic Tests Most accurate test is... • Electromyography – Shows decreased strength with repetitive stimulation Questions often ask “What imaging test should beQuestions often ask What imaging test should be done?” Answer... Chest “something!” – Chest X-ray, CT, or MRI are done to look for thymoma or thymic hyperplasia MTB S2CK  ‐ p. 297 Myasthenia Gravis/Treatment Best initial treatment is... • Neostigmine or pyridostigmine • Longer acting versions of edrophonium MTB S2CK  ‐ p. 297 Myasthenia Gravis/Treatment If meds don’t control disease, the “most appropriate next step in management” is... • Thymectomy if < 60 • If > 60 prednisone is used • Azothioprine, cyclophosphamide, or p , y p p , mycophenolate are used in order to get patient off steroids MTB S2CK  ‐ p. 298 27 Myasthenia Gravis/Treatment Acute myasthenic crisis • Severe, overwhelming disease • Profound weakness • Respiratory involvement • Treated with IVIG or plasmapheresis MTB S2CK  ‐ p. 298 1 Obstetrics and  Gynecology Jason M. Franasiak, MD Chief Resident Physician Obstetrics & Gynecology University of North Carolina Pregnancy Definitions Signs and Diagnosis of Pregnancy Ph i l i Ch i PPhysiologic Changes in Pregnancy Pregnancy • Pregnancy Symptoms – Amenorrhea – Breast tenderness – Nausea and vomiting – Fatigue • The surge in estrogen, progesterone, and beta- human chorionic gonadotropin (beta-HCG) leads to many symptoms of pregnancy MTB S2CK  ‐ p. 441 27-year-old woman with nausea and vomiting for 2 weeks. Symptoms worsen in the morning, but occur at any time during the day. She has a decrease in appetite. Her last menstrual period (LMP) was 6 weeks ago. Physical examination is unremarkable. Which is the best next step? a. Complete blood count Helpful for anemia, but p b. Beta-HCG c. HIDA scan d. Comprehensive metabolic panel e. Urinalysis MTB S2CK  ‐ p. 441  p ,not next step Not initial work-up for nausea/vomitting Important, but must diagnose causeImportant, but must diagnose cause Definitions Embryo Bi th InfantFetus MTB S2CK  ‐ p. 441 Birth 8 weeks gestation 1 year Fertilization Dating Methods • Developmental age (DA): Days since fertilization • Gestational age (GA): Days/weeks since the LMP – On average, 2 weeks longer than DA • Nägele rule: Estimate day of delivery – Take the first day of LMP, subtract 3 months then add 7 daysadd 7 days MTB S2CK  ‐ p. 442 Example: LMP = 7 / 1 / 2010 -3 +7 EDD = 4 / 8 / 2011 2 Trimester Breakdown DeliveryFertilization 24 weeks DA 26 weeks GA 12 weeks DA 14 weeks GA 1st Trimester 2nd Trimester 3rd Trimester • Frequent visits • Monitoring for labor• Genetic “triple” or MTB S2CK  ‐ p. 442 • FIRST screening • Fetal heart tones with doppler “quad” screen • Fetal movement at 16-20 weeks GA • Anatomic ultrasound at 18-20 weeks GA Term Lengths 42 weeks GA Fertilization 37 weeks 24 weeks Previable Preterm Term Postterm MTB S2CK  ‐ p. 442 GAGA G6P2124 Gravidity/Parity Gravity Number of Pregnancies Abortions Living Children MTB S2CK  ‐ p. 442‐443 F-PAL = Full-term (F); Preterm (P); Abortions (A); Living Children (L) Pregnancies Parity Full-term birth Preterm birth 20-year-old woman presents to the office because she believes she’s pregnant. Her sexual partner usually wears a condom, but didn’t 2 weeks ago. She is now 4 weeks late for her menstruation. Which of the following is a first sign of pregnancy? a. Quickening Not felt until second trimesterb. Goodell sign c. Ladin sign d. Linea nigra e. Chloasma MTB S2CK  ‐ p. 443  Seen at 6 weeks gestation Seen in second trimester Seen at 16 weeks gestation Signs of Pregnancy Sign Physical Finding Time from Conception Goodell sign Ladin sign Chadwick sign Softening of cervix Softening of uterine  midline  Blue discoloration of  vagina and cervix 4‐6 weeks 6 weeks 6‐8 weeks MTB S2CK  ‐ p. 444 Telangiectasias/  palmar erythema Chloasma Linea nigra Small blood vessels/  reddening of palms Hyperpigmentation of  the face, worse with sun Hyperpigmentation  down abdomen midline 1st trimester 16 weeks 2nd trimester Diagnostic Evaluation Beta-hCG • Urine and serum testing  all highly sensitive • Produced by cytotrophoblast or syncytiotrophoblast in placenta • First trimester Doubling every 48 hours for first 4 weeks– Doubling every 48 hours for first 4 weeks – Urine pregnancy tests are positive 4 weeks following the first day of LMP – Peak levels at 10 weeks gestation • Levels drop in 2nd trimester MTB S2CK  ‐ p. 444 3 Diagnostic Evaluation Step 2 Key Points  • Ultrasound confirms intrauterine pregnancy • At 5 weeks, or a beta-HCG of ≥1500 Image: X.Compagnion , commons.wikimedia.org IU/L, a gestational sac should be seen on ultrasound MTB S2CK  ‐ p. 444 Yolk Sac Gestational Sac Physiologic Changes in Pregnancy Cardiovascular changes •Cardiac output increases 30-50% •Lower blood pressure Decreased afterload Increased blood volume MTB S2CK  ‐ p. 444 Physiologic Changes in Pregnancy Gastrointestinal changes • “Morning sickness” – Caused by increase in estrogen, progesterone, and HCG made by placenta • Gastroesophageal reflux L h l hi t h d d t– Lower esophageal sphincter has decreased tone – Displacement of stomach by uterus • Constipation – Motility in large intestine decreased MTB S2CK  ‐ p. 445 Physiologic hydronephrosis in pregnancy Physiologic Changes in Pregnancy Genitourinary and Renal Changes • Increase in the size of kidney and ureters – Increased risk of pyelonephritis – Increased incidence of Image: Nevit Dilmen, WikiCommons stress urinary incontinence • Increase in GFR – Decrease in BUN/creatinine MTB S2CK  ‐ p. 445 Physiologic Changes in Pregnancy Hematology Changes • Increased... – RBCs – Plasma – Coagulation factors • Anemia – Plasma volume > RBCs MTB S2CK  ‐ p. 445 Physiologic Changes in Pregnancy Hematology Changes • Hypercoagulable state – Fibrinogen (Factor I) increases 50% along with fibrin split products (Factors VII, VIII, IX, X) – Protein C and S (inhibitors of coagulation) decrease – No increase in PT, PTT, or INR, , – Recall: Virchow triad MTB S2CK  ‐ p. 445 Hypercoagulation Endothelial Damage Stasis 4 Prenatal Care First Trimester Second Trimester Third Trimester Other Screening Tests • Visits every 4 to 6 weeks • Between 11 and 14 weeks – Ultrasound confirms gestational age and check for nuchal translucency Prenatal Care/First Trimester A thickened or enlarged nuchal translucency is an indication of Down syndrome. MTB S2CK  ‐ p. 445 Image: Dr. Wolfgang Moroder WikiCommons 17-year-old woman presents for routine prenatal checkup at 12 weeks. Which of the following is the most accurate method to establish gestational age? a. Ultrasound b. Beta-HCG  Levels vary widely c. Pelvic exam d. Fundal height e. LMP MTB S2CK  ‐ p. 445‐446 May change with multiple gestations y y May change with multiple gestations May be unreliable Prenatal Care/Second Trimester Genetic Screening: Risk of chromosomal anomalies • 15-20 weeks gestation • Triple screen – Maternal serum alpha-fetoprotein (MSAFP) – beta-HCG Estriol– Estriol • Quad screen – Inhibin A added to triple screen MTB S2CK  ‐ p. 446 Banana Sign • Increased MSAFP may indicate dating error, neural tube defect, or abdominal wall defect Prenatal Care/Second Trimester Banana Sign Ultrasound at 16 weeks showing banana sign created by compression MTB S2CK  ‐ p. 446 Image: Dr. W. Moroder, WikiCommons created by compression of cerebellum in posterior fossa due to neural tube defect. Prenatal Care/Second Trimester Landmarks in 2nd trimester: • Auscultation of fetal heart rate • 16 to 20 weeks: Quickening – Fetal movement first detected by mother M lti i li– Multiparous may experience earlier • Anatomic ultrasound – 18 to 20 weeks MTB S2CK  ‐ p. 446 5 Prenatal Care/Third Trimester • Visits are every 2 to 3 weeks until 36 weeks • Weekly visits after 36 weeks • Braxton-Hicks Contractions Oft d i 3rd t i t– Often occur during 3rd trimester – Sporadic and don’t cause cervical dilation – If they become regular, the cervix should be checked to rule out preterm labor before 37 weeks MTB S2CK  ‐ p. 446 Third Trimester Testing Week Test Action 27 24‐28 Complete blood  count Glucose challenge If hemoglobin  140 at one  hour perform oral MTB S2CK  ‐ p. 446 36 Cervical cultures for  Chlamydia and gonorrhea Rectovaginal culture for  group B Streptococcus hour, perform oral  glucose challenge test Treat if positive Prophylactic antibiotics  during labor Prenatal Care/Third Trimester • Glucose challenge test: Fasting or nonfasting ingestion of 50 g of glucose and serum glucose check 1 hour later • Glucose challenge test: Fasting serum glucose, ingestion of 100 g of glucose • Serum glucose checks at 1, 2, and 3 hours • Elevated glucose during any two of these tests is abnormal MTB S2CK  ‐ p. 447 Prenatal Care/Other Screening Tests Chorionic Villus Sampling • Done at 10 to 13 weeks • Obtains fetal karyotype • Catheter into intrauterine cavity to aspirate chorionic villi from placenta MTB S2CK  ‐ p. 447 Image: National Human Genome Research Institute, WikiCommons Prenatal Care/Other Screening Tests Amniocentesis • Done after 15-20 weeks • Obtains fetal karyotype • Needle placed transabdominally into i ti d ithd i tiamniotic sac and withdraw amniotic fluid MTB S2CK  ‐ p. 447 Prenatal Care/Other Screening Tests Percutaneous umbilical blood sample • In cases of Rh isoimmunization and when a fetal CBC is needed • Needle placed transabdominally into uterus to get blood from umbilical corduterus to get blood from umbilical cord MTB S2CK  ‐ p. 447 6 Ectopic Pregnancy Risk Factors Presentation Diagnosis Management 29-year-old woman with history of chlamydia and abnormal vaginal bleeding presents with left lower quadrant abdominal pain for the past eight hours. Her LMP was 6 weeks ago. Her temperature is 99°F, heart rate is 100 bpm, blood pressure is 130/80 mmHg, and respiratory rate is 13 breaths/minute. Which of the following is the most likely diagnosis?Which of the following is the most likely diagnosis? a. Ectopic pregnancy b. Menstrual cramps c. Diverticulitis d. Ovarian torsion e. Ovarian cyst MTB S2CK  ‐ p. 447‐448  Altered menstrual pattern present Does not cause vaginal bleeding • Pregnancy implants outside the uterus • Most commonly occurs in ampulla of fallopian tube Ectopic Pregnancy 70-80% Source: Kaplan Lecture Notes MTB S2CK  ‐ p. 448 Risk Factors • Previous ectopic pregnancies (strongest risk factor) • Pelvic inflammatory disease (PID) • Intrauterine devices (IUD) Ectopic Pregnancy/Risk Factors MTB S2CK  ‐ p. 448 Source: Nevit Dilmen, wikimedia commons Source: Gloecknerd, wikimedia commons Ectopic Pregnancy Presentation • Period of amenorrhea • Unilateral lower abdominal or pelvic pain • Vaginal bleeding • If ruptured can be hypotensive with• If ruptured, can be hypotensive with peritoneal irritation MTB S2CK  ‐ p. 448 Ectopic Pregnancy Differential diagnosis • Abortion • Acute appendicitis • Adnexal torsion • Corpus luteum cyst • Diverticulitis • Endometriosis • Gastroenteritis • PIDCorpus luteum cyst rupture PID • UTI 7 Ectopic Pregnancy Diagnostic Tests • Beta-hCG – Confirms pregnancy • Ultrasound – Locates implantation sitep • Laparoscopy: – Invasive test and treatment to visualize and remove the ectopic pregnancy MTB S2CK  ‐ p. 448 Ectopic Pregnancy/Transvaginal Ultrasound Uterus Bladder Ectopic pregnancy Image: Courtesy of Jason Franasiak, MD Ectopic Pregnancy/Treatment Ectopic Confirmed Ruptured Not Ruptured Surgical Treatment Medical Treatment MTB S2CK  ‐ p. 448 Stable Unstable IV fluids, blood products, dopamine Surgery (Laparoscopy) Ectopic Pregnancy/Medical Treatment > 15% drop in β-hCG Methotrexate given, β-hCG checked 4 & 7 days later Baseline labs: • CBC • LFTs • Kidney function • β-hCG < 15% drop in β-hCG MTB S2CK  ‐ p. 449 Observe for side effects, no other Rx necessary 2nd dose of methotrexate, β-hCG checked day 4 & 7 > 15% drop in β-hCG Persistently high β-hCG Surgical treatment Ectopic Pregnancy Exclusion Criteria for Methotrexate • Hemodynamically unstable patients • Signs of impending or ongoing ectopic mass rupture • Clinically important abnormalities in baseline hematologic, renal, or hepatic laboratory values • Immunodeficiency, active pulmonary disease, or peptic ulcer diseasedisease • Hypersensitivity to Methotrexate • Coexistent viable intrauterine pregnancy • Breastfeeding • Unwilling or unable to be compliant with post-therapeutic monitoring • Do not have timely access to a medical institution MTB S2CK  ‐ p. 449 Ectopic Pregnancy/Surgical Treatment SalpingostomySurgical Treatment Salpingectomy ostomy = cut ectomy = remove MTB S2CK  ‐ p. 449‐450 Images: Courtesy of Jason Franasiak, MD 8 Ectopic Pregnancy • Mothers who are Rh negative should receive anti-D Rh immunoglobulin (RhoGAM) to prevent hemolytic disease MTB S2CK  ‐ p. 450 Abortion 20-year-old woman presents to ED for vaginal bleeding and lower abdominal pain for one day. She states that she’s 15 weeks pregnant. T 99.0°F, HR 100 bpm, BP 110/75 mmHg, and RR 12/min. Pelvic exam, blood present in vault. Ultrasound shows intrauterine bleeding, products of conception, and dilated cervix. Which is the most likely diagnosis? a. Complete abortion b. Incomplete abortion c. Inevitable abortion d. Threatened abortion e. Septic abortion MTB S2CK  ‐ p. 450  We are going to review the definitions in this section Abortion • A pregnancy that ends < 20 weeks gestation or fetus weighs ≤ 500g • 80% of spontaneous abortions occur prior to 12 weeks gestation MTB S2CK  ‐ p. 450 Abortion Maternal factors that increase risk of abortion • Maternal age • Anatomic abnormalities MTB S2CK  ‐ p. 450 Source: Ed Uthman, MD., commons.wikimedia.org Abortion Source: RadsWiki, commons.wikimedia.org 9 Abortion 6 3 4 5 Source: Floranerolia, commons.wikimedia.org 1. Dye injector 2. Cervix 3. Uterus 4. Adhesions 5. Right Tube 6. Left Tube 2 1 4 Abortion Maternal factors that increase risk of abortion • Maternal Age • Anatomic abnormalities • Infections • Immunological factors (e.g. Anti-phospholipid syndrome or SLE) • Endocrinological factors • Malnutrition • Trauma MTB S2CK  ‐ p. 450 Abortion/Presentation Signs/Symptoms • Cramping abdominal pain • Vaginal bleeding • Hypotension • Tachycardia MTB S2CK  ‐ p. 450 Abortion/Diagnostic Tests • CBC • Blood type and Rh screen • Pelvic ultrasound MTB S2CK  ‐ p. 451 You cannot answer the “most likely diagnosis” question about abortion without an ultrasound Abortion/Types No products of conception Follow up in office Complete Incomplete Inevitable Threatened Missed Septic Products of conception intact, but intrauterine bleeding present and dilation of cervix D&C/Medical Death of fetus, but all products of conception present in the uterus D&C/M di l MTB S2CK  ‐ p. 451 Some products of conception Dilation & Curettage (D&C) / Medical Products of conception intact, intrauterine bleeding, No dilation of cervix Bed rest, pelvic rest D&C/Medical Infection of uterus and surrounding areas D&C and IV Antibiotics (levofloxacin & metronidazole) Abortion Mothers who’re Rh negative should also receive anti-D Rh immunoglobulin at this time MTB S2CK  ‐ p. 451 10 Multiple Gestations Multiple Gestations/Presentation Signs/Symptoms • Exponential growth of uterus • Rapid weight gain by mother • Elevated beta-HCG and Maternal S Al h F t t i (MSAFP)Serum Alpha-Fetoprotein (MSAFP) MTB S2CK  ‐ p. 451 Fertility drugs increase multiple gestations Multiple Gestations/Diagnostic Tests • Ultrasound visualizes fetus Monozygotic 1 egg and  1 sperm that splits Identical twins • Same gender • Same physical characteristics • Same blood type MTB S2CK  ‐ p. 452 Same blood type • Fingerprints differ Dizygotic 2 eggs and  2 sperm Fraternal twins • Different or same sex  • They resemble each other ‐ As any siblings would Multiple Gestations Source:Trlkly , commons.wikimedia.org Multiple Gestations/Diagnostic Tests Multiple Gestations • For monozygotic twins, amnionicity and chorionicity depend on timing of cleavage 11 Multiple Gestations Source: Kevin Dufendach, commons.wikimedia.org Multiple Gestations Complications • Spontaneous abortion of one fetus • Premature labor and delivery • Placenta previa • Anemia MTB S2CK   ‐ p. 452 Preterm Labor  28-year-old woman 28th week of pregnancy with severe lower back pain. The pain is cyclical and is increasing in intensity. On physical examination she seems to be in pain. T 98.9°F, HR 104 bpm, BP 135/80 mmHg, RR 15/min. Cervix is 3 cm dilated. Which of the following is the most likely diagnosis? a. Premature rupture of membranes b. Preterm labor c. Cervical incompetence d. Preterm contractions MTB S2CK  ‐ p. 452  Membranes intact Presents with contractions Cervical dilation present Preterm Labor • Preterm births occur < 37 weeks gestation – Spontaneous: preterm labor – Indicated: maternal or fetal • Preterm labor – Activation of hypothalamic-pituitary-adrenal yp p y (HPA) axis – Decidual hemorrhage – Inflammation – Uterine distension Preterm Labor/Risk Factors • Premature rupture of membranes • Multiple gestation • Previous history of preterm labor • Placental abruption • Maternal factorsMaternal factors – Uterine anatomical abnormalities – Infections MTB S2CK  ‐ p. 452‐453 12 Preterm Labor/Risk Factors MTB S2CK  ‐ p. 453 Source: RadsWiki, commons.wikimedia.org Preterm Labor/Risk Factors MTB S2CK  ‐ p. 453 Source: Ed Uthman, , commons.wikimedia.org Preterm Labor/Presentation +Contractions Cervical change • Occurring between 20 and 37 weeks gestation MTB S2CK  ‐ p. 453 Preterm Labor/Evaluation Initial evaluation • Gestational age • Fetal weight • Presenting fetal part MTS2CK  ‐ p. 453 Preterm Labor/Evaluation Indications for delivery • Maternal severe HTN • Maternal cardiac disease • Maternal cervical dilation > 4 cm • Maternal hemorrhage (abruptio placenta, DIC) • Fetal death • Chorioamnionitis • Preterm rupture of membranes (34 weeks) • Fetal distress • Intrauterine growth restriction with reverse diastolic flow When any of these is present, answer delivery MTS2CK  ‐ p. 453 Preterm Labor Preterm labor Stop delivery if • EGA 24-33 wks • EFW 600-2 500 g Delivery if • EGA 34-37 wks • EFW > 2 500 g MTS2CK  ‐ p. 453 • EFW 600-2,500 g • EFW > 2,500 g Betamethasone & Tocolytics 13 Preterm Labor/Corticosteroids Corticosteroids • Betamethasone or dexamethasone • Effects of betamethasone begin within 24 hours and peak at 48 hours GoalGoal • Decrease risk of RDS and neonatal mortality MTS2CK  ‐ p. 453 Corticosteriods increase surfactant and thus “mature” fetal lungs Preterm Labor/Tocolytics Goal • Delay preterm labor • Allows time for steroids to work • Transport to specialist unit Agents • Magnesium sulfate MTS2CK  ‐ p. 454 Preterm Labor Magnesium toxicity leads to respiratory depression & cardiac arrest, check deep tendon reflexes often! Toxicity: Give calcium gluconate MTS2CK  ‐ p. 454 Preterm Labor/Tocolytics Goal • Decrease contractions • Given to allow time for steroids to work AgentsAgents • Magnesium sulfate • Calcium-channel blockers • β-adrenergic agents • Prostaglandin synthetase inhibitors MTS2CK  ‐ p. 454 Preterm Labor/Tocolytics Source: commons.wikimedia.org Ductus Arteriosus Premature Rupture of   Membranes 14 Premature Rupture of Membranes (PROM) • The rupture of chorioamniotic membrane before onset of labor Diagnosis • Sterile speculum examination• Sterile speculum examination – Fluid pools in posterior fornix – Fluid turns nitrazine paper blue – When dry, fluid has ferning pattern MTS2CK  ‐ p. 454 Premature Rupture of Membranes MTS2CK  ‐ p. 454 Source: Elizabeth August, MD Premature Rupture of Membranes PROM can lead to • Preterm labor • Cord prolapse • Placental abruption ace a ab up o • Chorioamnionitis MTS2CK  ‐ p. 454‐455 PROM = Do fewer exams! Premature Rupture of Membranes/Treatment Before 32 weeks gestation • Corticosteroids • Antibiotics >37 weeks gestation, unknown GBS, > 18 hours rupture • Penicillin administered for prophylaxis 34-37 weeks gestation, unknown GBS34 37 weeks gestation, unknown GBS • Initiate Penicillin Known GBS negative • NO Antibiotics 15 Third‐Trimester Bleeding/Previa Placenta previa • Abnormal implantation of placenta over internal cevical os Ri k F t• Risk Factors – Previous uterine scar – Multiple gestations – Previous placenta previa MTS2CK  ‐ p. 456 24-year-old woman in her 32nd week of pregnancy presents to ED. She woke up in bed in a pool of blood. Denies contractions or pain. HR 105 bpm, BP 110/70 mmHg. Which is the next step? a. Digital vaginal exam Never do digital exam w/o knowing placental location b. Transabdominal ultrasound c. Immediate vaginal delivery d. Immediate cesarean delivery e. Transvaginal ultrasound MTS2CK  ‐ p. 455  Gather information first Abdominal US is safer knowing placental location Third‐Trimester Bleeding/Previa Source: Jason Franasiak, MD Third‐Trimester Bleeding/Previa Digital vaginal exam contraindicated in third trimester vaginal bleeding Can cause MTS2CK  ‐ p. 455 • Separation between placenta and uterus • Severe hemorrhage Third‐Trimester Bleeding/Previa Presentation • PAINLESS vaginal bleeding • Usually presents > 28 weeks Diagnosis • Transabdominal ultrasound –Placenta location MTS2CK  ‐ p. 456 Third‐Trimester Bleeding/Previa Types Partial covering of the internal cervical os, but th Fetal vessel present over cervical os Complete Partial Marginal Vasa Previa Low- lying Placenta MTS2CK  ‐ p. 456 Complete covering of the internal cervical os covers more than the marginal Marginal covering of the internal cervical os Placenta that’s implanted in lower segments of uterus but not covering internal cervical os 16 Third‐Trimester Bleeding/Previa Types Full moon Half moon Crescent moon MTS2CK  ‐ p. 456 Third‐Trimester Bleeding/Previa Types Umbilical cord Source: Sigrid de Rooij, comons.wikimedia.org MTS2CK  ‐ p. 457 Fetal vessels Internal os Placenta Third‐Trimester Bleeding/Treatment Treatment of placenta previa • Strict pelvic rest • Type and screen, CBC • Fetal considerations • Delivery by C-section – Labor – Severe hemorrhage – Fetal distress MTS2CK  ‐ p. 457 Third‐Trimester Bleeding/Accreta Placental invasion (based on depth) • Accreta • Increta • Percreta MTS2CK  ‐ p. 457‐458 Third‐Trimester Bleeding MTS2CK  ‐ p. 458 Third‐Trimester Bleeding/Accreta Placental invasion (based on depth) • Accreta • Increta • Percreta Risk Factors • Placenta previa • Prior uterine scars MTS2CK  ‐ p. 457 17 Placental Abruption Third‐Trimester Bleeding/Abruption Placental abruption • Abnormal, premature separation of placenta from uterus Effects • Complete – Life-threatening • Partial – Minor bleedg bleeding – Premature delivery – Uterine tetany – DIC And – Hypovolemic shock – No clinical signs/symptoms MTS2CK  ‐ p. 458 Placental Abruption/Etiology Risk factors • Maternal HTN (chronic, preeclampsia, eclampsia) • Prior placental abruption T b d/ i• Tobacco and/or cocaine use • Trauma MTS2CK  ‐ p. 458 Placental Abruption/Presentation Clinical presentation • Vaginal bleeding • Severe abdominal PAIN (uterine tenderness) C t ti• Contractions • Possible fetal distress MTS2CK  ‐ p. 458 Placental Abruption/Presentation Late Decelerations Source: Jason Franasiak, MD Placental Abruption/Diagnostic Tests Diagnosis • Transabdominal ultrasound • Clinical scenario Placenta previa = painLESS vaginal bleeding Placental abruption = painFUL vaginal bleeding MTS2CK  ‐ p. 459 18 Placental Abruption/Diagnostic Tests Source: Nevit Dilman commons.wikimedia.org Placental Abruption Type Description Complications Concealed • Blood within uterine  cavity  • Placenta more likely  to be completely  detached Serious complications:  • DIC • Uterine tetany • Fetal hypoxia  • Fetal death  • Sheehan syndrome MTS2CK  ‐ p. 459 External • Blood drains through  cervix  • Placenta more likely  to be partially  detached   Sheehan syndrome  (postpartum  hypopituitarism) Usually smaller with minimal  complications   Placental Abruption/Treatment Delivery plan • Cesarean delivery – Uncontrollable hemorrhage – Fetal distress • Vaginal delivery – Placental separation is limited – Fetal heart tracing is assuring – Fetal death prior to presentation MTS2CK  ‐ p. 459 Placental Abruption/Treatment Mothers who are Rh negative should also receive anti-D Rh immunoglobulin at this time MTB S2CK  ‐ p. 451 Uterine Rupture Uterine Rupture • Spontaneous complete transection of uterus from endometrium to serosa • Usually occurs during labor Life threatening to mother and baby MTS2CK  ‐ p. 459 Life-threatening to mother and baby Immediate delivery! 19 Uterine Rupture/Risk Factors Risk factors • Previous C-section – Classical: higher risk of uterine rupture – Low transverse • Trauma • Uterine myomectomy• Uterine myomectomy • Uterine overdistention – Polyhydramnios – Multiple gestations • Placenta percreta MTS2CK  ‐ p. 460 Uterine Rupture MTS2CK  ‐ p. 460 Types of cesarean scars. Source: Elizabeth August, MD. Uterine Rupture/Presentation Clinical presentation: • Extreme abdominal pain • Abnormal bump in abdomen • Lack of uterine contractions • Regression of fetus MTS2CK  ‐ p. 460 Uterine Rupture/Treatment Treatment • Emergent laparotomy and delivery • Repair of uterus or hysterectomy Future management Early delivery via C section• Early delivery via C-section MTS2CK  ‐ p. 461 Uterine rupture requires immediate laparotomy and delivery of the fetus Rh Incompatability Rh Incompatibility Rh incompatibility • Mother RhD negative • Baby RhD positive • Leads to isoimmunization Rh isoimmunization • Fetal RBCs cross placenta • Maternal antibodies to RhD antigen are made MTS2CK  ‐ p. 461 20 Rh Incompatibility Clinical significance • 1st pregnancy: mild anemia/hyperbilirubinemia • 2nd pregnancy: maternal antibodies attack the second Rh positive baby MTS2CK  ‐ p. 461 Leads to hemolysis of fetal RBCs  Hemolytic disease of newborn Rh Incompatibility Hemolytic Disease of Newborn • Fetal anemia • Extramedullary production of fetal RBCs • Hemolysis   heme and bilirubin levels MTS2CK  ‐ p. 461 Neurotoxicity from hyperbilirubinemia High output cardiac failure  Hydrops fetalis Rh Incompatibility Rh Antibody Screening Rh PositiveRh Negative No further screening Antibody titer MTS2CK  ‐ p. 461 screening Sensitized Further Monitoring Unsensitized Repeat at 28 weeks and give Rhogam as indicated Rh Incompatibility Antibody screen: if mother is Rh– or Rh+ Antibody titer: how many maternal antibodies to Rh+ blood MTS2CK  ‐ p. 461 Rh Incompatibility Rhogam indications for Rh “unsensitized patients” • 28 weeks gestation • Delivery • Procedures (amniocentesis)( ) • Bleeding (abortion, abruption) MTS2CK  ‐ p. 461‐462 Unsensitized = no anti-Rh antibodies present Rh Incompatibility Antibody Screen Positive • Antibody titer • Titer ≥ 1:4  “Sensitized” • Titer ≥ 1:16  consider treatment l ithalgorithm MTS2CK  ‐ p. 462 21 Rh Incompatibility Antibody titer ≥ 1:16 Determine paternal Rhesus type Homozygote Positive Heterozygote or unsure Homozygote Negative MTS2CK  ‐ p. 462 or unsure paternity Treatment algorithm Fetal genotyping performed on samples of chorionic villi, amniocytes or fetal blood No Treatment g Rh Incompatibility Antibody titer ≥ 1:16 Fetus is Rh Antigen Positive Middle Cerebral Artery Dopplers Peak MCA Velocity is >1 5 MOM MTS2CK  ‐ p. 462.3 >1.5 MOM (Multiples of median) Cordocentesis with transfusion if fetal Hct is 22 29-year-old woman G2P1 in her 30th week of pregnancy presents for routine prenatal visit. Her wedding ring is getting too tight. BP 150/100 mmHg, HR 92 bpm, RR 12, T 99°F. Urine 1+ protein. LFTs: normal. Which is the most likely diagnosis? a. Chronic hypertension b. Gestational hypertension c. HELLP syndrome d. Preeclampsia e. Eclampsia MTS2CK  ‐ p. 463  No laboratory abnormalities No proteinuria Pre-eclampsia + seizures Hypertension/Chronic  Chronic HTN • BP ≥ 140/90 mmHg before 20 weeks gestation • Treatment – Labetalol, nifedipine, or methyldopa MTS2CK  ‐ p. 463 ACE inhibitors and ARBs cause fetal malformations Don’t use during pregnancy Hypertension/Gestational Gestational HTN • BP ≥ 140/90 mmHg after 20 weeks gestation • No proteinuria T t t• Treatment –Labetalol, nifedipine, or methyldopa – Only during pregnancy MTS2CK  ‐ p. 463 Hypertension/Preeclampsia Mild preeclampsia Severe preeclampsia Hypertension  Proteinuria  Edema  l > 140/90 Dipstick 1+ to  2+; 24‐hour  urine > 300 mg Hands, feet, face > 160/110 Dipstick 3+; 24‐hour  urine > 5 g Generalized MTS2CK  ‐ p. 463 Mental status  changes  Vision changes  Impaired liver  function   No No No     Yes Yes Yes  Hypertension/Preeclampsia Preeclampsia Risk Factors • Nulliparity • Multiple gestation • Advanced maternal age • Chronic HTN • Renal disease • History of preeclampsia MTS2CK  ‐ p. 463 Hypertension/Preeclampsia Preeclampsia Mild BP > 140/90 mmHg Proteinuria 1+ to 2 + Severe BP > 160/110 Proteinuria 3+ to 4+ At term Preterm I d 1. Prevent Eclampsia MTS2CK  ‐ p. 464 Induce delivery 1. Betamethasone a. Mature fetus’ lungs 2. Magnesium sulfate a. Seizure prophylaxis p a. Magnesium sulfate 2. Control BP a. Hydralazine 3. Delivery a. Preterm b. Term 23 Hypertension/Preeclampsia The only definitive treatment in preeclampsia is delivery MTS2CK  ‐ p. 464 in preeclampsia is delivery Hypertension/Eclampsia Eclampsia • Tonic-clonic seizures occurring in patient with preeclampsia Treatment St bili th• Stabilize mother – Seizure control: magnesium – BP control: hydralazine and labetalol • Deliver baby MTS2CK  ‐ p. 464 Hypertension ‐ HELLP HELLP Syndrome • Hemolysis, Elevated Liver enzymes, Low Platelets TreatmentTreatment • Stabilize mother – BP control: hydralazine and labetalol • Deliver baby MTS2CK  ‐ p. 464 Gestational Diabetes 28-year-old woman in her 27th week of gestation presents for routine prenatal visit. No complaints. T 99°F, BP 120/80 mmHg, HR 87 bpm. The patient is given 50 mg of glucose. An hour later, blood glucose 145 mg/dL. Which is the best next step? a. Treat with insulin The 1h GTT is a screening test b. Treat with sulfonylurea c. Do a fasting blood glucose level d. Perform oral glucose tolerance test MTS2CK  ‐ p. 464‐465  A 3h GTT is needed Pregestational Diabetes Pregestational diabetes • Diabetes before pregnancy • Either Type 1 or Type 2 DM MTS2CK  ‐ p. 465 24 Pregestational Diabetes Maternal Complications • Preeclampsia • Spontaneous abortion • Increased rate of infection • Increased postpartum hemorrhage MTS2CK  ‐ p. 465 Pregestational Diabetes Fetal Complications • Congenital anomalies • Macrosomia – Shoulder dystocia P t l b• Preterm labor MTS2CK  ‐ p. 465 Pregestational Diabetes/Evaluation Additional prenatal testing • EKG • 24-hour urine for baseline renal function • HbA1C • Ophthalmological exam MTS2CK  ‐ p. 465 Pregestational Diabetes DM type  Route of administration  Insulin type Type 1  Type 2 Insulin pump Subcutaneous insulin  NPH NPH, lispro Oral Medications • Metformin and glyburide MTS2CK  ‐ p. 465 Age (weeks) Pregestational Diabetes/Fetal Testing  Weekly nonstress test (NST) and ultrasound Lecithin/sphingomyelin ratio (L/S ratio) NST: fetal well-being Ultrasound: fetal size L/S ratio: assess fetal lung maturity test (if mat re deli er ) 32-36 >36 37 38-39 MTS2CK  ‐ p. 466 Twice-weekly testing; one NST and one biophysical profile (BPP) Continue testing, IOL at 39 weeksNST: fetal well-being BPP: amount of amniotic fluid and fetal well- being (if mature → delivery) Gestational Diabetes/Complications Gestational diabetes (GDM) • Glucose intolerance identified during pregnancy Complications • Preterm birth F t l i• Fetal macrosomia • Birth injuries from fetal macrosomia • Neonatal hypoglycemia • Development of overt Type 2 DM postpartum MTS2CK  ‐ p. 466 25 Gestational Diabetes/Complications Erb’s Palsy Klumpke’s Palsy Gestational Diabetes/Evaluation Diagnosis • Routine screening between 24 and 28 weeks GA • 1-hour glucose tolerance test Positi e if > 140 mg/dL– Positive if > 140 mg/dL • 3-hour glucose tolerance test MTS2CK  ‐ p. 466 No Gestational Diabetes Glucose load test Non-fasting ingestion of 50g glucose followed by serum measurement one hour later < 140 mg/dL > 140 mg/dL Oral glucose tolerance testNO gestational diabetes MTS2CK  ‐ p. 467 All glucose levels are normal Fasting ingestion of 100 mg of glucose followed by serum glucose measurements at 1, 2, and 3 hours after ingestion Elevation of serum glucose at 1, 2, or 3 hours No further test diabetes Gestational diabetes Diabetes/Treatment Treatment • Diabetic diet and exercise (walking) • Medical management – Insulin – Oral hypoglycemics Don’t tell pregnant patients to lose weight. It’s the most common wrong answer. Once patients are put on insulin they should follow fetal testing schedule starting at 32 weeks. MTS2CK  ‐ p. 467 Diabetes/Treatment Gestational diabetes needs formal 2-hour GTT postpartum to screen Type 2 DM MTS2CK  ‐ p. 467 Fetal Growth Abnormalities Intrauterine Growth Restriction Macrosomia 26 Intrauterine Growth Restriction • Fetuses with intrauterine growth restriction (IUGR) weigh in bottom 10% for gestational age Type Symmetric Characteristic Brain in proportion with rest of body Types of IUGR  MTS2CK  ‐ p. 467‐468 Symmetric  Asymmetric Brain in proportion with rest of body  Occurs  20 weeks   Intrauterine Growth Restriction/Etiology • Chromosomal abnormalities • Neural tube defects • Infections (viral, protozoans) • Multiple gestations • Maternal disease – HTN or renal disease – Malnutrition – Substance abuse – Hemoglobinopathies MTS2CK  ‐ p. 468 Intrauterine Growth Restriction Physical examination Fundal height = gestational age in weeks Example: a patient’s fundal height at 28 weeks should be 28 cm Diagnosis • Ultrasound done to confirm gestational age and fetal weight MTS2CK  ‐ p. 468 Intrauterine Growth Restriction Source: Jason Franasiak, M.D. Intrauterine Growth Restriction Source: Jason Franasiak, M.D. Intrauterine Growth Restriction Source: Jason Franasiak, M.D. 27 Intrauterine Growth Restriction Complications • Premature labor • Stillbirth • Fetal hypoxia • Lower IQ • Seizures • Mental retardation MTS2CK  ‐ p. 468 Intrauterine Growth Restriction Treatment/Prevention • Quit smoking • Prevent maternal infection with immunizations D t i ti l d li ti• Determine optimal delivery time MTS2CK  ‐ p. 468 Macrosomia/Risk Factors Macrosomia • Estimated birth weight > 4500 g Risk factors M t l di b t b it• Maternal diabetes or obesity • Advanced maternal age • Post term pregnancy • Fetal genetic syndromes MTS2CK  ‐ p. 468 Macrosomia/Diagnostic Tests Physical examination Fundal height = gestational age in weeks Example: a patient’s fundal height at 28 weeks should be 28 cm Macrosomia • Fundal height ≥ 3 cm greater than GA MTS2CK  ‐ p. 469 28 weeks should be 28 cm Macrosomia/Diagnostic Tests Physical Examination • Fundal height ≥ 3 cm than GA  Ultrasound Ultrasound confirms the estimated weight by • Femur lengthFemur length • Abdominal circumference • Head circumference and biparietal diameter MTS2CK  ‐ p. 469 Intrauterine Growth Restriction Source: Jason Franasiak, M.D. 28 Intrauterine Growth Restriction Source: Jason Franasiak, M.D. Intrauterine Growth Restriction Source: Jason Franasiak, M.D. Macrosomia Complications • Shoulder dystocia • Birth injuries • Low Apgar scores • Hypoglycemia MTS2CK  ‐ p. 469 Shoulder Dystocia/ Clavicle Fracture Source: Nevit Dilman, commons.wikimedia.org Gestational Diabetes/Complications Erb’s Palsy Klumpke’s Palsy Macrosomia Treatment • Induction of labor – Lungs mature – EFW < 4500 grams Cesarean deli er• Cesarean delivery – EFW > 5000 grams MTS2CK  ‐ p. 469 29 Labor and Delivery Fetal Testing Electronic Fetal Monitoringg Physiologic Changes Before Labor Induction of Labor Nonstress Test • Allows for evaluation of fetal well-being in utero MTS2CK  ‐ p. 469 Source: Jason Franasiak, MD Nonstress Test MTS2CK  ‐ p. 469 Source: Jason Franasiak, MD Biophysical Profile • Biophysical profile (BPP) Test Score NST Fetal Breathing 0 or 2 0 or 2 MTS2CK  ‐ p. 470 g Fetal Movement Tone Amniotic Fluid 0 or 2 0 or 2 0 or 2 Electronic Fetal Monitoring MTS2CK  ‐ p. 470 Source: Jason Franasiak, MD Electronic Fetal Monitoring MTS2CK  ‐ p. 470 Source: Jason Franasiak, MD 30 Electronic Fetal Monitoring Type Description Cause Early  decelerations Variable  decelerations  Decrease in heart rate that  occurs with contractions Decrease in heart rate and  return to baseline with no  relationship to contractions Head  compression Umbilical cord  compression MTS2CK  ‐ p. 470 Late  decelerations  (most serious  and dangerous) relationship to contractions Decrease in heart rate after  contraction started. No  return to baseline until  contraction ends Fetal hypoxia Electronic Fetal Monitoring MTS2CK  ‐ p. 471 Electronic Fetal Monitoring Electronic Fetal Monitoring Physiological Changes Before Labor Early Changes • Lightening • Braxton-Hicks contractions • Bloody show MTS2CK  ‐ p. 471 Stages of Labor Labor & Delivery Onset of labor → full dilation of cervix Full dilation of cervix → delivery of neonate Delivery of neonate → delivery of placenta Primipara: 6–18 h Multipara: 2–10 h Primipara: 2 h Stage 1 Stage 2 Stage 3 MTS2CK  ‐ p. 471 Onset of labor → 4 cm dilation 4 cm dilation → full dilation placentap Primipara: 6–7 h Multipara: 4–5 h Primipara: 1.2 cm/h (minimum) Multipara: 1.5 cm/h (minimum) p Multipara: 1 h 30 minLatent phase Active phase 31 Labor & Delivery Monitoring (Stage 1) • Maternal BP and pulse • Electronic fetal monitor: fetal HR and uterine contractions E i i ( 2 h )• Examine cervix (every 2 hours) – Cervical dilation – Cervical effacement – Fetal station MTS2CK  ‐ p. 471 Labor & Delivery NOT effaced NO dilation Fully effaced 1 cm dilated Source: Fred the Oyster, commons.sikimedia.org 5 cm dilation Fully dilated at 10 cm Labor & Delivery MTS2CK  ‐ p. 472 Stages of fetal head descent. Source: Elizabeth August, MD. Labor & Delivery Stage 2 • Cervix fully dilated to delivery –Internal vs. External Fetal Monitoring Labor & Delivery Internal vs. External Fetal Monitoring Source: Jason Franasiak, MD Labor & Delivery Internal vs. External Fetal Monitoring Source: Jason Franasiak, MD Source: Jason Franasiak, MD 32 Labor & Delivery Stage 2 • Cervix fully dilated to delivery –Internal vs. External Fetal Monitoring –Rupture of amniotic membranes • Spontaneous or artificial –Meconium Labor & Delivery Stage 2: Cervix is fully dilated to delivery • Cardinal Movements of Labor 1. Engagement 2. Descent 3 Flexion3. Flexion 4. Internal Rotation 5. Extension 6. External Rotation 7. Expulsion MTS2CK  ‐ p. 472‐473 Labor & Delivery Stage 3 • From delivery of neonate to placenta Immediately after delivery • Repair lacerations of vagina Signs of placental separation include: • Fresh bleeding from vagina • Umbilical cord lengthening • Uterine fundus rising • Uterus becoming firm MTS2CK  ‐ p. 473 Operative Delivery Operative Vaginal Delivery • Forceps • Vacuum C-section Operative Delivery MTS2CK  ‐ p. 460 Types of cesarean scars. Source: Elizabeth August, MD. Induction of Labor/Medications Induction of labor • Initiating labor via medical means Medications • PGE2 used for cervical ripening • Oxytocin MTS2CK  ‐ p. 473 33 Induction of Labor/Medications Mechanical means • Amniotomy • Foley Balloon MTS2CK  ‐ p. 473 Inspect for a prolapsed umbilical cord after puncturing amniotic sac Complications of Labor  and Delivery Prolonged Latent StageProlonged Latent Stage Protracted Cervical Dilation Arrest Disorders Malpresentation Shoulder Dystocia Postpartum Hemorrhage 22-year-old primipara in 39th week of pregnancy, with intense abdominal pain that’s intermittent. Gush of fluid felt 3 hours ago. Cervix 3 cm dilated, 50% effaced, and fetus’ head is felt at –2 station. The next 3 hours she progresses, her cervix is 5 cm dilated, 60% effaced, and fetal head at –1 station. Six hours after presentation, her cervix is 5 cm dilated and 60% effaced, fetal head at 0cervix is 5 cm dilated and 60% effaced, fetal head at 0 station. Which is the most likely diagnosis? a. Prolonged latent stage b. Protracted cervical dilation c. Arrest of descent d. Arrest of cervical dilation MTS2CK  ‐ p. 474  Cervix has not dilated Cervix has not dilated Fetal head has descended Prolonged Latent Stage Prolonged latent stage • Latent phase ≥ 20 hours for primipara • Latent phase ≥ 14 hours for multipara EtiologyEtiology • Sedation • Unfavorable cervix • Uterine dysfunction with irregular/weak contractions MTS2CK  ‐ p. 474 Prolonged Latent Stage Treatment of Prolonged Latent Phase • Rest • Hydration MTS2CK  ‐ p. 474 Most will convert to spontaneous delivery in 6 to 12 hours Protracted Cervical Dilation Stage 1 of labor • < 1.2 cm/hour in primipara • < 1.5 cm/hour in multipara Etiology: 3 P’s MTS2CK  ‐ p. 474‐475 Power: strength and frequency of contractions Passenger: size and position of fetus Passage: size of pelvis 34 Protracted Cervical Dilation Treatment of protracted cervical dilation • Power –Pitocin –Amniotomy • Passenger/Pelvis –C-section MTS2CK  ‐ p. 475 Arrest Disorders/Types Arrest of Cervical Dilation • No cervical dilation for 2 hours Arrest of Fetal Descent • No fetal descent for 1 hour MTS2CK  ‐ p. 475 Arrest Disorders/Etiology Etiology • Cephalopelvic disproportion – Cesarean delivery • Excessive sedation/anesthesia – Rest or reversal • Malposition – Time – Operative delivery (forceps) – Cesarean delivery MTS2CK  ‐ p. 475 25-year-old woman in 35th week of gestation presents for routine prenatal checkup. T 98°F, BP 130/90, HR 87, and RR 12. Her abdomen is gravid. A hard circular surface is felt in proximal part of the uterus. Which is the next step? a. External cephalic version b. Ultrasound c. CT scan d. X-ray MTS2CK  ‐ p. 475  Perform ultrasound first Ultrasound is used to determine position Malpresentation/Presentation Presenting Part • Part of fetal body that’s closest to vaginal canal and will be engaged when labor starts • Cephalic• Cephalic –Head • Malpresentation –Foot or buttock MTS2CK  ‐ p. 476 Malpresentation/Presentation Diagnosis • Physical Examination – Leopold maneuvers – Vaginal exam Ultraso nd• Ultrasound MTS2CK  ‐ p. 476. Should always confirm suspected diagnosis on physical examination with ultrasound 35 Types of Breech Presentation Type Description Frank breech  Complete  b h Fetus hips are flexed with extended  knees bilaterally Fetus hips and knees are flexed  bil ll MTS2CK  ‐ p. 476 breech Footling  breech bilaterally Fetus feet are first  • one leg (single footling)  or  • both legs (double footling) Malpresentation/Presentation MTS2CK  ‐ p. 476 Source: Elizabeth August, MD. Malpresentation/Presentation MTS2CK  ‐ p. 477 Source: Elizabeth August, MD. Malpresentation/Presentation MTS2CK  ‐ p. 477 Source: Elizabeth August, MD. Malpresentation/Treatment Treatment • External cephalic version • C-section MTS2CK  ‐ p. 477 Shoulder Dystocia Shoulder dystocia • Entrapment of anterior shoulder behind pubic symphisis after delivery of fetal head MTS2CK  ‐ p. 477 36 Shoulder Dystocia MTS2CK  ‐ p. 478 Source: Elizabeth August, MD. Shoulder Dystocia/Risk Factors Risk Factors • Maternal diabetes • Maternal obesity • Post-term pregnancy • History of prior shoulder dystociaHistory of prior shoulder dystocia MTS2CK  ‐ p. 478 Any factor that indicates fetus is too big or the pelvis is too small is a risk factor for shoulder dystocia Shoulder Dystocia/Treatment Treatment 1. McRoberts Maneuver MTS2CK  ‐ p. 478‐479 Shoulder Dystocia/Treatment MTS2CK  ‐ p. 478 McRobert’s maneuver. Source: Elizabeth August, MD. Shoulder Dystocia/Treatment Treatment 1. McRoberts maneuver 2. Rubin maneuver 3. Woods maneuver 4. Delivery of posterior arm 5. Deliberate fracture of fetal clavicle 6. Zavanelli maneuver MTS2CK  ‐ p. 478 Postpartum Hemorrhage/Etiology Postpartum hemorrhage • More than 500 mL after delivery • Early vs. late postpartum bleeding Etiologygy • Uterine atony • Laceration • Retained products of conception • Coagulopathy MTS2CK  ‐ p. 479 “a” = without “tony” = contractions 37 Postpartum Hemorrhage/Risk Factors Risk factors for atony • Anesthesia • Uterine overdistention • Prolonged/rapid labor • Augmented labor • Uterine leiomyoma • Preeclampsia with magnesium therapy MTS2CK  ‐ p. 479 Postpartum Hemorrhage/Treatment Evaluation/Treatment • Examination of perineum, vagina, and cervix • Bimanual examination of uterus (+/- compression/massage) • Administer uterotonics (oxytocin, methylergonovine maleate, 15 methyl-PGF2alpha/Hemabate, misoprostol) • Operative management – Uterine artery embolizationy – D&C – Bakri balloon placement • Collapsed silicone ballon inserted in uterus, later filled with fluid – B-Lynch stitch – Uterine artery ligation – Hysterectomy MTS2CK  ‐ p. 479 Postpartum Hemorrhage/Treatment B-Lynch Suture Uterine Artery Ligation Source: Niels Olson, commons.wikimedia.org Modified: Jason Franasiak, MD Postpartum Hemorrhage/Treatment Evaluation/Treatment • Examination of perineum, vagina, and cervix • Bimanual examination of uterus • Administer uterotonics • Operative managementOperative management • Blood products – PRBCs, FFP, Cryoprecipitate Postpartum Hemorrhage/Treatment Product Contents Effect Packed RBCs FFP RBCs, WBCs, plasma Soluble plasma  proteins ↑ Hct 3% ↑ Hgb 1g/dL ↑ fibrinogen 10  mg/dL Cryoprecipitate Platelets p Factors VIII and XIII,  fibrinogen,  fibronectin, vWF Platelets, RBCs,  WBCs, plasma g/ ↑ fibrinogen 10  mg/dL ↑ 5000 – 10,000/mm3 per  unit The Uterus Premenstrual Syndrome Menopause AUB/DUB Contraception 38 PMS/PMDD Premenstrual syndrome (PMS) • Physical, mood-related, and behavioral changes Premenstrual Dysphoric Disorder (PMDD) • Severe form of PMS MTB S2CK  ‐ p. 481 PMS/PMDD • Over 200 symptoms attributed to PMS • Common symptoms – Headache B t t d ( t d i )– Breast tenderness (mastodynia) – Pelvic pain, bloating – Irritability, lack of energy MTB S2CK  ‐ p. 481 PMS/PMDD Diagnostic criteria • Present for 2 consecutive cycles • Symptom-free in first part of cycle • Symptoms present in second half of cycle • Dysfunction in social or economicDysfunction in social or economic performance MTB S2CK  ‐ p. 481 PMS/PMDD Treatment of PMS/PMDD • Lifestyle – Limit caffeine, alcohol, cigarettes, and chocolate – Aerobic exercise – Increase calcium and magnesium • Pharmacologic – NSAIDs – Severe: SSRIs MTB S2CK  ‐ p. 481 Menopause  Menopause • Permanent cessation of menses • Due to permanent cessation of estrogen production M di f t 51• Median age of onset: 51 MTB S2CK  ‐ p. 482 Menopause  Physiology • Early – The oocytes produce less estrogen and t • Late – Changes in sex hormones • Testosterone progesterone – LH and FSH start to rise – Shortening of menstrual cycles • Androstenedione • Estrone • Estradiol 39 Menopause  Symptoms • Menstrual irregularity • Sweats and hot flashes • Mood changes • Dyspareunia (pain during sexual intercourse)Dyspareunia (pain during sexual intercourse) MTB S2CK  ‐ p. 482 Women are symptomatic for an average of 12 months, but some experience symptoms for years Menopause  Physical Examination • Decrease in breast size • Vaginal/cervical atrophy • Uterovaginal prolapse MTB S2CK  ‐ p. 482 Atrophic vaginitis: vaginal epithelium is estrogen dependent. The absence of estrogen causes thinning, presents as itching, burning, and/or dyspareunia. Menopause/Osteoporosis Vertebral body fractures. Source: Dr Robert CARLIER, CHU Raymond Poincaré, Garches, France, commons.wikimedia.org Menopause  Hormone replacement therapy (HRT) • Estrogen +/- progesterone • Contraindications – Estrogen-dependent carcinoma – History of PE or DVT MTB S2CK  ‐ p. 482 HRT associated with endometrial hyperplasia, can lead to endometrial carcinoma Abnormal Uterine Bleeding   •Heavy, prolonged menstrual bleeding • “Gushing” of blood •Clots may be seen •Endometrial Menorrhagia Hypomenorrhea Intermenstrual bleeding •Endometrial polyps •Endometrial/cervical cancer •Exogenous estrogen d i i t ti Metrorrhagia MTB S2CK  ‐ p. 482‐483 hyperplasia •Uterine fibroids •Dysfunctional uterine bleeding • Intrauterine device • Light menstrual flow • May only have spotting •Obstruction (hymen, cervical stenosis) •OCPs administration Abnormal Uterine Bleeding   Irregular bleeding • Time intervals • Duration Menometrorrhagia Menstrual cycles > 35 days long •Pregnancy •Menopause •Significant weight loss (anorexia) T ti t Oligomenorrhea Postcoital bleeding MTB S2CK  ‐ p. 483 u at o • Amount of bleeding •Endometrial polyps •Endometrial/cervical cancer •Exogenous estrogen administration •Malignant tumors •Tumor secreting estrogen Bleeding after intercourse •Cervical cancer •Cervical polyps •Atrophic vaginitis 40 Abnormal Uterine Bleeding   Uterine fibroid Source: James Heilman, MD, commons.wikimedia.org Abnormal Uterine Bleeding   Postcoital bleeding is cervical cancer until proven otherwise Any patient > 35 with abnormal bleeding should undergo endometrial biopsy to rule out endometrial carcinoma MTB S2CK  ‐ p. 482‐483 Abnormal Uterine Bleeding   Normal squamous cells HPV infects cells causing mild dysplasia Source: Ed Uthman MD, commons.wikimedia.org Abnormal Uterine Bleeding  Anovulatory Uterine Bleeding • Estrogen produced • No progesterone – No ovulation  no corpus luteum  no progesteroneprogesterone – Prevents withdrawal bleeding Abnormal Uterine Bleeding Diagnosis/Evaluation • CBC • Pregnancy test • PT/PTT • Pelvic ultrasoundPelvic ultrasound • Endometrial biopsy • Pap smear • Thyroid studies • Prolactin levels Dysfunctional Uterine Bleeding  • Dysfunctional uterine bleeding (DUB) –Unexplained abnormal bleeding There’s no specific test for DUB Diagnosis by exclusion MTB S2CK  ‐ p. 483 41 Dysfunctional Uterine Bleeding Treatment of DUB • Oral contraceptive pills (OCP) • Cyclic progesterone Long-term • Endometrial ablation • Hysterectomy Acute hemorrhage • D&C • IV estrogen MTB S2CK  ‐ p. 484 Dysfunctional Uterine Bleeding Source: Hic et nunc, commons.wikimedia.org Dysfunctional Uterine Bleeding Source: Hic et nunc, commons.wikimedia.org Contraception/Female Condoms  Advantages • Offer some protection against HIV and STDs • Under female control DisadvantagesDisadvantages • Not as effective as other methods • They are larger and bulkier than male condoms MTB S2CK  ‐ p. 484 Contraception/Female Condoms  MTB S2CK  ‐ p. 484 Source: : ka Grzywacz, commos.wikimedia.org Contraception/Vaginal Diaphragm MTB S2CK  ‐ p. 484 Source: Axefan2, commons.wikimedia.org 42 Contraception/Cervical Cap Source: Ceridwen, commons.wikimedia.org Source: Dake, commons.wikimedia.org Contraception/Vaginal Diaphragm Advantages • Under female control Disadvantages • Need to be fitted properlyNeed to be fitted properly • Requires advance preparation • Improper placement or dislodging reduces efficacy MTB S2CK  ‐ p. 484 Contraception/Oral Contraceptive Pills  MTB S2CK  ‐ p. 484 Source; Matthew Bowden, commons.wikimedia.org Contraception/Oral Contraceptive Pills  Hormones • Combination of both estrogen and progestin • Progestin only UseUse • 21 days of active pill • 7 days placebo • Menses occurs during 7 days of placebo pills MTB S2CK  ‐ p. 484 Contraception/Oral Contraceptive Pills  Advantages • Effective with perfect use • Reduces rates of ovarian and endometrial cancer • Easily reversibley Disadvantages • User dependent • Risk of thromboembolism MTB S2CK  ‐ p. 484 Contraception/Vaginal Ring • A flexible vaginal ring inserted in vagina – Releases both estrogen and progesterone – Remains in place for 3 weeks The aginal ring has similar side effects• The vaginal ring has similar side effects and efficacy to OCPs MTB S2CK  ‐ p. 485 43 Contraception/Transdermal Patch • Transdermal patch – Combination of estrogen and progesterone – Placed on skin for 7 days Patches sho ldn’t be placed on breast• Patches shouldn’t be placed on breast • Side effects and efficacy = OCPs MTB S2CK  ‐ p. 485 Contraception/Transdermal Patch MTB S2CK  ‐ p. 485 Source : Keitei, commons.wikimedia.org Contraception/Injectable • Depo-Medroxyprogesterone Acetate (DMPA) –IM injection –Every 3 months Contraception/Implantable Implant contraceptive system • Releases progestin daily • Inhibits ovulation and thickens cervical mucus Contraception/Intrauterine Device  • Intrauterine device (IUD) – Copper device – Levonorgestrel device • Most commonly used worldwide• Most commonly used worldwide • Most effective aside from sterilization MTB S2CK  ‐ p. 485 Contraception/Intrauterine Device  MTB S2CK  ‐ p. 485 Source: Gloecknerd, commons.wikimedia.org 44 Contraception/Intrauterine Device  Source: Nevit Dilmen ,commons.wikimedia.org Contraception/Sterilization • Tubal Ligation/Occlusion • Vasectomy MTB S2CK  ‐ p. 485 Vulva and Vagina Vulva and Vagina/Labial Fusion Fusion • Occurs when excess androgens are present – Exogenous – Endogenous MCC of labial fusion is 21-B Treatment • Conservative • Reconstructive surgery MTB S2CK  ‐ p. 485 hydroxylase deficiency Vulva and Vagina/Epithelial Abnormalities  Abnormality Age group  affected  Description Treatment Lichen  sclerosus  Squamous  Any age  If postmenopausal,   increased concern  for cancer Any age; patients  White, thin skin  from labia to  perianal area,  “parchment “ Patients with  Topical  steroids Sitz baths or  MTB S2CK  ‐ p. 486 q cell  hyperplasia   Lichen  planus y g p who’ve had chronic  vulvar pruritus 30s–60s    chronic irritation  develop hyper‐ keratosis (raised  white lesion) Pruritic, polygonal,  papular and  Purple lubricants  (relieve  pruritus) Topical  steroids    Vulva and Vagina/Bartholin Gland Cyst Bartholin Glands • Location: lateral sides of vulva • Function: secrete mucus Bartholin Gland Cyst/Abscessy • Presents with pain, tenderness, and dyspareunia • Edema and inflammation with deep fluctuant mass MTB S2CK  ‐ p. 486 45 Vulva and Vagina/Bartholin Gland Cyst Clitoris Labia Minora Urethra Skene’s glandsg Vagina Bartholin’s glands Source: Nicholasolan, commons.wikimedia.org Vulva and Vagina/Bartholin Gland Cyst Bartholin Abscess • Simple incision and drainage (I&D) • Word catheter placement – 4-6 weeks duration – Small rubber catheter, inflatable balloon tip is inserted into cyst incision after the contents ofinserted into cyst incision, after the contents of the cyst have been drained • Recurrence: marsupialization or excision MTB S2CK  ‐ p. 486 During I&D, fluid released should be cultured for STDs (e.g., Neisseria gonorrhea and Chlamydia trachomatis) 19-year-old woman with vaginal pruritus and discharge for one week. Discharge is green and profuse. She’s had multiple sexual partners in past 2 months. LMP 2 weeks ago. Wet mount: motile flagellates. Which is the most likely diagnosis? a. Chlamydia b. Bacterial vaginosis c. Neisseria gonorrhoeae d. Candidiasis e. Trichomonas vaginalis MTB S2CK  ‐ p. 486‐487  Clue cells on wet mount Dx w/ culture or DNA probe Hyphae on wet mount Vaginitis/Risk Factors  Vaginitis: spectrum of conditions Risk factors • Antibiotic use (Lactobacillus normally keeps vaginal pH < 4 5)keeps vaginal pH < 4.5) • Diabetes • Overgrowth of normal flora MTB S2CK  ‐ p. 487 Types of Vaginitis Trichomonas (most common nonviral STD) Bacterial vaginosis Gardnerella •Vaginal discharge with fishy odor; Candidiasis Candida albicans •White, cheesy vaginal discharge •Potassium Trichomonas vaginalis •Profuse, green, frothy vaginal MTB S2CK  ‐ p. 487 gray white •Saline prep: clue cells •Metronidazole or clindamycin hydroxide (KOH): pseudohyphae; vaginal culture is most specific •Miconazole or clotrimazole, econazole, or nystatin discharge •Saline prep: motile flagellates •Treat both patient and partner with metronidazole Vaginitis Trichomonas: partners need to be treated MTB S2CK  ‐ p. 487 46 Vaginitis/Gardnerella Clue cells. Source: Per Grinsted, commos.wikimedia.org Vaginitis/Candida albicans Source: Nephron, commons.wikimedia.org Vaginitis/Trichomonas vaginalis Trichomonas. Source: cdc.gov Trichomonas. Source: Alex Brollo, commons.wikimedia.org Vulva/Malignant Disorders Paget Disease • Intraepithelial neoplasia • Most common in postmenopausal Caucasians PresentationPresentation • Vulvar soreness and pruritus • Appears as a red lesion with superficial white coating MTB S2CK  ‐ p. 487 Vulva/Malignant Disorders Large cells with clear cytoplasm in epidermis Source: Nephron, commons.wikimedia.org Vulva/Malignant Disorders • Biopsy is needed for definitive diagnosis Treatment • Wide local excision or vulvectomy • 2 cm margin is optimal MTB S2CK  ‐ p. 487 47 Vulva/Malignant Disorders Squamous Cell Carcinoma • Most common type of vulvar cancer Presentation • Pruritus, bloody vaginal discharge, and postmenopausal bleedingpostmenopausal bleeding • Exam: ranges from a small ulcerated lesion to large cauliflower-like lesion A biopsy is essential for diagnosis MTB S2CK  ‐ p. 488 Staging of Squamous Cell Carcinoma  Stage Findings 0  I  II  III  Carcinoma in situ Limited to vaginal wall  2 cm Tumor spreading to lower urethra or anus,  il l l h d MTB S2CK  ‐ p. 488 IV  IVa unilateral lymph nodes present Tumor invasion into bladder, rectum, or  bilateral lymph nodes Distant metastasis      Vulva/Malignant Disorders Treatment • Unilateral: modified radical vulvectomy • Bilateral: radical vulvectomy • Lymph nodes that’re involved must undergo lymphadenectomy MTB S2CK  ‐ p. 488 Uterine Abnormalities Uterine Abnormalities/Adenomyosis Adenomyosis • Invasion of endometrial glands into myometrium • Typically between ages of 35 and 50 Risk factors • Endometriosis• Endometriosis • Uterine fibroids Presentation • Dysmenorrhea and menorrhagia MTB S2CK  ‐ p. 488 Uterine Abnormalities/Adenomyosis Diagnosis • Clinical diagnosis • Physical examination – Uterus is large, globular, boggy • MRI Treatment • Hysterectomy - only definitive treatment MTB S2CK  ‐ p. 488 48 Uterine Abnormalities/Adenomyosis Source: Hic et nunc, commons.wikimedia.org Uterine Abnormalities/Adenomyosis Source: Hic et nunc, commons.wikimedia.org Uterine Abnormalities/Endometriosis Endometriosis • Endometrial tissue outside of endometrial cavity • Most common sites are ovary and pelvic peritoneum • Endometriosis occurs in women of reproductiveEndometriosis occurs in women of reproductive age • More common if first-degree relative has endometriosis MTB S2CK  ‐ p. 488 Uterine Abnormalities/Endometriosis Presentation • Cyclical pelvic pain • Abnormal bleeding • Infertility Physical examination • Nodular uterus • Adnexal mass MTB S2CK  ‐ p. 488‐489 Dysmenorrhea and dyspareunia are common in endometriosis Uterine Abnormalities/Endometriosis Source: Julie M. Hastings, Asgerally T. Fazleabas, commons.wikimedia.org MTB S2CK  ‐ p. 489‐490 Uterine Abnormalities/Treatment  Mild disease • NSAIDs • Combined OCPs Severe disease • Danazole • Leuprolide acetate (leupron) • Surgery MTB S2CK  ‐ p. 489 49 Uterine Abnormalities/Treatment  Source: Hic et nunc, commons.wikimedia.org Ovarian Abnormalities Polycystic Ovarian Syndrome/Symptoms  Presentation • Amenorrhea or irregular menses • Hirsutism and obesity • Acne • Insulin resistance MTB S2CK  ‐ p. 489 MCC of androgen excess and hirsutism Polycystic Ovarian Syndrome/Diagnosis   Diagnostic test • Pelvic ultrasound • Elevated free testosterone • LH to FSH ratio > 3:1 MTB S2CK  ‐ p. 489‐490 Polycystic Ovarian Syndrome/Diagnosis   Uterus Source: Schomyny, commons.wikimedia.org Ovary Polycystic Ovarian Syndrome/Diagnosis   50 Polycystic Ovarian Syndrome/Treatment Treatment • Weight loss • OCPs • Spironolactone (hirsutism) • Metformin (insulin resistance) • Clomiphene (infertility) MTB S2CK  ‐ p. 490 1 Oncology Emma Holliday MDEmma Holliday, MD Resident Physician  Radiation Oncology University of Texas MD Anderson Cancer Center Breast Cancer Presentation Diagnosisg Genetic Tests Treatment Breast Cancer/Presentation • Most often found by patient • Found in asymptomatic women - On screening mammography - By palpation of a mass Hard immobile fixed to the chest wallHard, immobile, fixed to the chest wall MTB S2CK  ‐ p. 347 Breast Cancer/Presentation • Painless lump • Skin changes • Nipple retraction • Nipple discharge MTB S2CK  ‐ p. 347 Source:http://www.4woman.gov/faq/cancer- illustrations-with-t.gif Breast Cancer/Diagnostic Tests Biopsy is the best initial test Different methods are: • Fine needle aspiration (FNA) – Best initial biopsy Core needle biopsy• Core needle biopsy – Tells receptor status • Open surgical biopsy – Most accurate test MTB S2CK  ‐ p. 347 Breast Cancer/Diagnostic Tests Mammography • Screen the general population starting at age 50 MTB S2CK  ‐ p. 347 2 A woman finds a hard, nontender breast mass on self-examination. There is no alteration of the mass with menstruation. She is scheduled to undergo a FNA biopsy. Which of the following is most likely to benefit the patient? a. Mammography b. BRCA testing c. Ultrasound d. Bone scan e. PET scan MTB S2CK  ‐ p. 348  Confirms an extra risk of cancer Tells cystic vs solid To exclude bone metastases To look for metastatic disease When Is Ultrasound the Answer? • Clinically indeterminate mass lesions. It tells cysts versus solid lesions Answer ultrasound if the lesion: • Is painful• Is painful • Varies in size or pain with menstruation MTB S2CK  ‐ p. 348 When Is PET Scan the Answer? • Determines content of abnormal lymph nodes that are not easily accessible to biopsy. Cancer increases uptake on PET scan. MTB S2CK  ‐ p. 348 How do you tell the content of an abnormal, inaccessible lesion without biopsy? Try PET scan. When Is PET Scan the Answer? For example: • 80-year-old woman with biopsy-proven breast cancer has no nodes with cancer in the axilla. The primary lesion is small and the woman may not need adjuvant chemotherapy. Chest CT shows an j py abnormal hilar lymph node. MTB S2CK  ‐ p. 348 When Is BRCA Testing the Answer? • BRCA associated with increased risk of breast cancer, particularly within families • BRCA associated with ovarian cancer • What is not clear is what to do when BRCA is positive BRCA not shown to add mortality benefitpositive. BRCA not shown to add mortality benefit MTB S2CK  ‐ p. 348 The precise utility of MRI for breast cancer is not yet clear. When Is Sentinel Lymph Node Biopsy  the Answer? • When you want to know how likely it is that the breast cancer has spread MTB S2CK  ‐ p. 349 Source:http://www.cancer.gov/ncicancerbulletin/022211/page2 3 When Are Estrogen and Progesterone  Receptors Tested? • Estrogen receptor (ER) and progesterone receptor (PR) testing is routine for all patients • Hormone manipulation therapy is done if either test is positive MTB S2CK  ‐ p. 349 Breast Cancer/Treatment Surgery Options • Lumpectomy • Modified Radical Mastectomy • Radical Mastectomy • Radical mastectomy is always the wrong answer • Lumpectomy + Radiation is JUST AS GOOD as modified radical mastectomy MTB S2CK  ‐ p. 349 Hormonal Manipulation • All ER or PR positive patients should receive: – Tamoxifen – Raloxifene – Aromatase inhibitors (anastrazole, letrozole, exemestane) – If all are among the answer choices, aromatase inhibitors are the answer to the “most likely to benefit the patient” question MTB S2CK  ‐ p. 349 Breast Cancer/Treatment • Know the differences in side effects: Tamoxifen rarely gives endometrial cancer and clots (tamoxifen is a selective ER modifier). MTB S2CK  ‐ p. 349 ) Aromatase inhibitors give osteoporosis (aromatase inhibitors inhibit estrogen effect everywhere, even the good effects, like on bone density). When Is Trastuzumab the Answer? • All breast cancers should be tested for HER 2/neu. This is an abnormal estrogen receptor • Those who are positive should receive anti- HER 2/neu antibodies known as trastuzumab • Trastuzumab decreases the risk of recurrent disease MTB S2CK  ‐ p. 350 When Is Chemotherapy  the Answer? • Neoadjuvant means therapy given BEFORE the definitive treatment. Goal is to decrease cancer burden • Adjuvant means an additional therapy to clean up presumed microscopic cancer cells too small in amount to be detected MTB S2CK  ‐ p. 350 4 When Is Adjuvant Chemotherapy  the Answer? Adjuvant chemotherapy is the answer when: • Lesions >1 cm • Positive axillary lymph nodes found Use tamoxifen when MTB S2CK  ‐ p. 350 Use tamoxifen when multiple first-degree relatives have breast cancer. It lowers the risk of breast cancer. We do not know what to do about BRCA when it is positive. Breast Cancer/Treatment All of these definitely lower mortality: • Mammography • ER/PR testing, then tamoxifen/raloxifene • Aromatase inhibitors MTB S2CK  ‐ p. 350 • Adjuvant chemotherapy • Lumpectomy and radiation • Modified radical mastectomy • Trastuzumab (anti-Her 2/neu) • Prophylaxis with tamoxifen Prostate Cancer Presentation Treatment Screening Prostate Cancer/Presentation • Obstructive symptoms • Palpable mass • Elevated or rising PSA MTB S2CK  ‐ p. 350 Source:http://www.cancer.gov/cancertopics/pdq/treatment/prostate/Patient/page2 Prostate Cancer • Biopsy is the best initial test and the most accurate test. MTB S2CK  ‐ p. 350 Half of men above age 80 have prostate cancer on autopsy. Source:http://kidney.niddk.nih.gov/kudiseases/pubs/i magingut/ Prostate Cancer/Treatment • Prostatectomy • Radiation therapy • Brachytherapy • Hormonal therapy Watchful waiting• Watchful waiting MTB S2CK  ‐ p. 350‐351 5 Prostate Cancer/Treatment • Prostatectomy has slight benefit over radiation in terms of survival Most common complications of prostatectomy are:prostatectomy are: – Erectile dysfunction – Urinary incontinence MTB S2CK  ‐ p. 350‐351 Gleason Grading • Gleason Score = Tumor Grade • High Gleason grade suggests greater benefit of surgical g removal of the prostate • Get it out before it metastasizes if the Gleason grade is high MTB S2CK  ‐ p. 351 Source:http://www.training.seer.cancer.gov/prostate/abstract-code- stage/morphology.html Hormonal Manipulation in Prostate Cancer • Flutamide – Competitive inhibitor of testosterone & DHT • Leuprolide, goserelin – GNRH agonists: downregulates LH & FSH K t l• Ketoconazole – Suppresses testosterone • Orchiectomy – Stops endogenous production MTB S2CK  ‐ p. 351 Management That Is Definitely  Not Beneficial in Prostate Cancer These answers are ALWAYS wrong: • “Screening” imaging study like ultrasound • Lumpectomy • Chemotherapy • Hormonal manipulation to prevent recurrencesHormonal manipulation to prevent recurrences MTB S2CK  ‐ p. 351 Prostate Specific Antigen (PSA) PSA is controversial: • No mortality benefit with PSA • PSA is not to be routinely offered • Normal PSA does not exclude prostate cancer • High PSA doesn’t always mean prostate cancer MTB S2CK  ‐ p. 351 The higher the PSA, the greater the risk of cancer. PSA corresponds to the volume of cancer. Prostate Specific Antigen (PSA) • If question specifically says, “The patient is requesting PSA to screen for cancer,” then the answer is do the test MTB S2CK  ‐ p. 351 6 Elevated PSA Algorithm Elevated PSA Palpable mass No palpable mass Biopsy the mass Transrectal ultrasound MTB S2CK  ‐ p. 351 p y Mass seen Biopsy the mass No mass seen Multiple blind biopsies Lung Cancer Lung Cancer Who can get surgery? • Size of the tumor alone does not determine whether or not it can be resected – Large tumors can be resected with… Demonstration of suffficient residual lung• Demonstration of suffficient residual lung volume by PFTs • It is solitary and surrounding tissue is healthy – Small tumors cannot be resected if PFTs indicate poor lung function MTB S2CK  ‐ p. 352 Surgery Source:http://www.cancer.gov/cancertopics/pdq/treatment/non- small-cell-lung/Patient/page4 Source:http://www.cancer.gov/cancertopics/pdq/treatment/non -small-cell-lung/Patient/page4 Source:http://www.cancer.gov/cancertopics/pdq/treatment/n on-small-cell-lung/Patient/page4 Lung Cancer Surgery is not possible in these cases: • Bilateral disease • Malignant pleural effusion • Heart, carina, aorta, or vena cava is involved • Small cell cancer is considered unresectable in 95% of cases because it is metastatic or spread outside one lung MTB S2CK  ‐ p. 352 Ovarian Cancer Screening Diagnosisg Treatment 7 Ovarian Cancer • No screening test for ovarian cancer • Presentation: – Woman >50 years old Increasing abdominal girth– Increasing abdominal girth • No history of liver disease – Weight loss, fatigue MTB S2CK  ‐ p. 352 Ovarian Cancer/Diagnosis • The initial test is an ultrasound or CT scan MTB S2CK  ‐ p. 352 Source: James Heilman, MD, http://en.wikipedia.org/wiki/File:POvarianCA.png Source:http://www.cancer.gov/cancertopics/pdq/treatment/ovaria nepithelial/Patient/page1 Ovarian Cancer/Diagnosis • Most accurate test is biopsy MTB S2CK  ‐ p. 352 Source: http://en.wikipedia.org/wiki/File:Ovarian_carcinoma.JPG Ovarian Cancer/Treatment • The only cancer in which removing large amounts of locally metastatic disease benefits patient • Remove all visible tumor and pelvic organs and give chemotherapy MTB S2CK  ‐ p. 352 Testicular Cancer Presentation Diagnosisg Treatment Testicular Cancer/Presentation • Young men: 20-40 years old • Painless lump in the scrotum – Next best step? • Transillumination • Scrotal Ultrasound – Differential diagnosis?e e a d ag os s • Epididymitis • Hematocele • Varicocele MTB S2CK  ‐ p. 352 8 Testicular Cancer/Diagnosis Diagnostic Testing • Remove the whole testicle with inguinal orchiectomy • Do not cut the scrotum, hi h d thwhich can spread the disease • Needle biopsy of the testicle is always a wrong answer MTB S2CK  ‐ p. 352 Source:Ed Uthman, MD. http://en.wikipedia.org/wiki/File:Seminoma_of_the_Testis.jpg Testicular Cancer/Diagnosis • Seminoma – Has NORMAL AFP – Can have elevated bHCG – LDH correlated with disease burden • Non-seminoma – Yolk sac or Endodermal sinus • AFP – Embryonal • AFP and bHCG – Choriocarcinoma • AFP and bHCG – Teratoma • AFP and bHCG Testicular Cancer/Staging • Staging is performed with: – CT scan of the abdomen, pelvis, and chest – Lymphatic channels in the retroperitoneum spread testicular cancer into the chest MTB S2CK  ‐ p. 353 http://emedicine.medscape.com/article/437966-clinical#a0218 Testicular Cancer/Treatment • 1st- orchiectomy • 2nd- radiation • 3rd- chemotherapy Testicular cancer is one of the only• Testicular cancer is one of the only malignancies in which chemotherapy can cure widely metastatic disease, including spread into the brain MTB S2CK  ‐ p. 353 Cervical Cancer Prevention/early detection Clinical Presentation Treatment Prevention of Invasive Cervical Cancer • Human papillomavirus (HPV) vaccine is given to all women between ages 11 and 26 • Pap smear is performed starting at age 21 – Every 3 years, with Source:http://www.cdc.gov/cancer/dcpc/prevention/vaccination.htm y y , cytology, until 30 years old – After age 30, every 5 years, if HPV testing added – Stop at age 65 with adequate screening history and low risk MTB S2CK  ‐ p. 353 Source: Nephron, http://en.wikipedia.org/wiki/File:Adenocarcinoma_on_pap_test_1.jpg 9 Detection of Cervical Cancer • Atypical squamous cells of undetermined significance (ASCUS) – HPV testing • If positive  colposcopy and biopsy • If negative  repeat Pap in 6 mo • Low-grade and high-grade dysplasia g g g y p – Colposcopy and biopsy MTB S2CK  ‐ p. 353 Detection of Cervical Cancer Pap smear does not lower mortality as much as mammography or colonoscopy. MTB S2CK  ‐ p. 353 Cervical Cancer/Presentation • Asymptomatic – Detected on Pap • Symptomatic – Abnormal vaginal bleeding – Post coital bleeding – Abnormal discharge – Pelvic pain or fullnessp – Dysuria Cervical Cancer • The management of early cervical cancer = hysterectomy Source: Hic et nunc, http://en.wikipedia.org/wiki/File:Scheme_hysterectomy-en.svg 1 Ophthalmology  Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Ophthalmology   Conjunctivitis The Red Eye (Ophthalmologic Emergencies) Cataracts Diabetic Retinopathy Retinal Artery & Vein Occlusion Retinal Detachment Macula Degeneration Comparison of Viral and Bacterial  Conjunctivitis  Viral conjunctivitis Bacterial conjunctivitis Bilateral  Watery discharge  Easily transmissible  Normal vision Unilateral Purulent, thick discharge Poorly transmissible  Normal vision MTB S2CK  ‐ p. 497 Normal vision  Itchy  Preauricular adenopathy No specific therapy Normal vision Not itchy No adenopathy Topical antibiotics Conjunctivitis Viral conjunctivitis Bacterial conjunctivitis © David C Cogan Ophthalmic Pathology Collection Source: phil.cdc.gov Conjunctivitis The “must know” subjects in ophthalmology are: • The red eye (emergencies) • Diabetic retinopathyDiabetic retinopathy • Artery and vein occlusion • Retinal detachment MTB S2CK  ‐ p. 497 Etiologies of The Red Eye Discharge Autoimmune diseases Normal pupils Conjunctivitis Presentation Eye findings Most  Uveitis Photophobia Pain Glaucoma Fixed midpoint pupil Trauma Abrasion Feels like sand in eyes MTB S2CK  ‐ p. 498 Clinical diagnosis Topical antibiotics accurate test Best initial  therapy Slit lamp examination Topical steroids Tonometry •Acetazolamide •Mannitol •Pilocarpine •Laser trabeculoplasty Fluorescein stain •No specific therapy •Patch not clearly beneficial 2 Glaucoma/Chronic Glaucoma • Most often asymptomatic • Diagnosed by screening • Confirmation with tonometry • Elevated intraocular pressure MTB S2CK  ‐ p. 498 Glaucoma/Chronic Glaucoma Treat to decrease production of aqueous humor or  increase drainage • Prostaglandin analogues – Latanaprost – Travoprost – Bimatoprost • Topical beta blockers • Topical carbonic anhydrase inhibitors – Dorzolamide – Brinzolamidep – Timolol – Carteolol – Metipranolol – Betaxolol Or – Levobunolol • Alpha-2 agonists – Apraclonidine • Pilocarpine • Laser MTB S2CK  ‐ p. 498 Glaucoma/Acute Angle‐Closure Glaucoma Look for… • Sudden onset • Extremely painful, red eye hard to palpation • Walking into dark room precipitates pain because of pupillary dilationp p y • Pupil doesn’t react to light because it’s stuck • Cup-to-disc ratio > 0.3 MTB S2CK  ‐ p. 498 Glaucoma/Acute Angle‐Closure Glaucoma Conjunctival vessels dilated at corneal edge Author:Jonathan Trobe, M.D. Source: commons.wikimedia.org Hazy cornea Glaucoma/Acute Angle‐Closure Glaucoma Diagnosis • Confirmed with tonometry Treatment • IV acetazolamideIV acetazolamide • IV mannitol (osmotically draws of fluid out) • Pilocarpine & beta blockers constrict pupil & enhance drainage • Laser iridotomy MTB S2CK  ‐ p. 498 Herpes Keratitis • Infection of cornea • Eye is red, swollen, and painful, but don’t use steroids • Steroids markedly increase production of virusof virus • Fluorescein stain confirms dendritic pattern MTB S2CK  ‐ p. 499 3 Herpes Keratitis Treatment • Oral acyclovir, famciclovir, or valacyclovir • Topical trifluridine or idoxuridine MTB S2CK  ‐ p. 499 • Beware of steroid use for herpes keratitis • Steroids worsen condition Cataracts • No medical therapy for cataracts • Surgically remove lens & replace with new intraocular lens • New lens may automatically have bifocal capabilitycapability • Early cataracts are diagnosed with an ophthalmoscope or slit-lamp exam • Advanced cataracts visible on exam MTB S2CK  ‐ p. 499 Cataracts © nih.gov Diabetic Retinopathy • Annual screening exams INDISPENSIBLE!!!! • Detects retinopathy before visual loss occurs • Nonproliferative or “background” retinopathy is managed by controlling glucose level • Most accurate test is… – Fluorescein angiography– Fluorescein angiography • Proliferative: treated with laser photocoagulation • Vascular endothelial growth factor inhibitors (VEGF) injected in some patients to control neovascularization MTB S2CK  ‐ p. 499 Diabetic Retinopathy • Vitrectomy may be necessary to remove a vitreal hemorrhage obstructing vision MTB S2CK  ‐ p. 499 New blood vessel formation obscures vision. Source: Conrad Fischer, MD. Retinal Artery and Vein Occlusion Both present with… • Sudden onset monocular visual loss • Can’t make diagnosis without retinal examination • No conclusive therapy for either condition MTB S2CK  ‐ p. 500 4 Retinal Artery Occlusion MTB S2CK  ‐ p. 500 Retinal artery occlusion presents with sudden loss of vision and a pale retina and dark macula. Source: Conrad Fischer, MD. Retinal Vein Occlusion MTB S2CK  ‐ p. 500 Retinal vein occlusion leads to extravasation of blood into the retina. Source: Conrad Fischer, MD. Retinal Artery and Vein Occlusion Treatment of artery occlusion attempted with... • 100% oxygen • Acetazolamide to  intraocular pressure • Thrombolytics Mac la is described as MTB S2CK  ‐ p. 500 Macula is described as “cherry red”in artery occlusion because the rest of retina is pale Retinal Detachment Caused by… • Trauma • Extreme myopia (changes shape of eye) • Diabetic retinopathy Anything that pulls on retina can detach it• Anything that pulls on retina can detach it Presents with… • Sudden onset of painless, unilateral loss of vision • Described as “curtain coming down” MTB S2CK  ‐ p. 501 Retinal Detachment Reattachment by mechanical methods • Surgery, laser, cryotherapy • Injection of expansile gas pushes retina back up against globe of eye MTB S2CK  ‐ p. 501 Sudden painless loss of vision “like a courtain coming down.” Source: Conrad Fischer, MD. Macular Degeneration • MCC of blindness in older persons in U.S. • Idiopathic • Atrophic (dry) type and neovascular (wet) type • Far more common in older patients • Bilateral N l t l f• Normal external appearance of eye • Central vision lost MTB S2CK  ‐ p. 501 5 Macular Degeneration Neovascular disease • More rapid • More severe • New vessels grow between retina and underlying Bruch’s membrane • Neovascular or wet type causes 90% of permanent• Neovascular or wet type causes 90% of permanent blindness from macular degeneration MTB S2CK  ‐ p. 501 Atrophic macular degeneration has no proven effective therapy Macular Degeneration MTB S2CK  ‐ p. 502 Macular degeneration can be diagnosed only by visualization of the retina. Source: Conrad Fischer, MD. Macular Degeneration Best initial therapy for neovascular disease • VEGF inhibitors – Ranibizumab or bevacizumab • Injected directly into vitreous chamber every few weeksevery few weeks • Over 90% stop progression • 1/3 improve vision MTB S2CK  ‐ p. 502 1 Pediatrics Ryan Close, MD MPH Resident Physician Internal Medicine‐Pediatrics Hospital of the University of Pennsylvania  Routine Management  of the Newborn  Physical ExamPhysical Exam Apgar Score Eye Care  Routine Screening and Prevention Heart Rate (HR) Respiratory Rate  (RR) Physical Exam • Physical exams start with vital signs... Adults Newborns 60‐100 BPM 12‐24 BrPM 120–160 BPM 40‐60 BrPM Systolic Blood  Pressure (SBP) Diastolic Blood  Pressure (DBP) MTB S2CK – p. 403   120 mmHg 80 mmHg 65 mmHg 50 mmHg Apgar Score • Important part of physical exam • Translates physical exam into a “score” –Used for management decisions –Provides both short- and long-term prognostic indicatorsprognostic indicators MTB S2CK – p. 404   Apgar Score • Scores calculated at 1 minute and 5 minutes • Score at 1 minute – Represents conditions during labor and delivery – Indicates need for resuscitation • Score at 5 minutes – Represents effectiveness of resuscitation efforts – Prognostic of survival MTB S2CK – p. 404   Apgar Score 0 points 1 point 2 points Blue all over  100 bpm S h Appearance • Skin color Pulse  • Rate G i MTB S2CK – p. 404   No response None Absent Grimace/  feeble cry Some flexion Weak, irregular Sneeze, cough,  loud cry Active  movement Strong Grimace • Reflex & irritability Activity  • Muscle tone Respiration • Breathing 2 Apgar Score  • Low Apgar score isn’t predictive of cerebral palsy • Knowing differences in management if Apgar score is low MTB S2CK – p. 404  No signs of respiratory distress / high Apgar score A 28-year-old G1PO woman delivers a 3.9 kg male infant whose Apgar scores are 9 and 10 at 1 and 5 minutes, respectively. The delivery was uncomplicated, and both mother and child are in no acute distress. What’s the most appropriate first step upon delivery of this patient? a. Intubate the child  Patient is stable No need for decompression No evidence of infection or sepsis What we are not told: - Is this child term, or pre-term? - Vital signs ? MTB S2CK – p. 403   b. Send cord blood for arterial blood gas (ABG) c. Suction the mouth and nose d. Nasogastric tube (NGT) placement e. Give prophylactic antibiotics Prevention/Eye Care A 3.9 kg male infant whose Apgar scores were 9 and 10 at 1 and 5 minutes, respectively, presents five days after delivery because of red eyes. The delivery was without any complications. What is the most likely diagnosis at day 5 of life? a. Chemical irritation b. Neisseria gonorrhoeae c. Chlamydia trachomatis d. Group-B Streptococci e. Herpes simplex Prevention/Eye Care Chemical Irritation - Erythromycin ointment - Tetracycline ointment - Silver nitrate drops Due to Neisseria gonorrhea Chlamydia trachomatis Herpes Simplex Gram MTB S2CK – p. 404‐405   Due to silver nitrate Developing countries Not an allergy Gram- negative diplococci Treat with ceftriaxone Prevent with ointments Not effectively prevented by prophylaxis ointments Treat with oral erythromycin Treat with systemic acyclovir and topical vidarabine Prevention/Eye Care A 3.9 kg male infant whose Apgar scores were 9 and 10 at 1 and 5 minutes, respectively, presents five days after delivery because of red eyes. The delivery was without any complications. What is the most likely diagnosis at day 5 of life? a. Chemical irritation b. Neisseria gonorrhoeae c. Chlamydia trachomatis d. Group-B Streptococci e. Herpes simplex Prevention & Screening/Vitamin K Deficiency Vitamin K deficient bleeding = hemorrhagic disease of newborn • Neonate colon lacks normal bacterial flora that produces vitamin K • Vitamin K is responsible for clotting factors II, VII, IX, and X as well as proteins C and S, p • Treatment: one IM injection of vitamin K – Oral doses will not work MTB S2CK – p. 405   Inactive Clotting Factors Vit K Active Clotting Factors 3 Prevention & Screening/Vitamin K Deficiency XI XIa XIIa IX IXa VIII VIIIa X TF VIIa VII Intrinsic Pathway Extrinsic Pathway VIII Xa V Va II IIa Fibrinogen Fibrin“Thrombin” Prevention & Screening/Testing Newborns should be screened for: • Phenylketonuria (PKU) • Congenital adrenal hyperplasia (CAH) • Biotinidase • Beta-thalassemia G l t i MTB S2CK – p. 405 – 406   • Galactosemia • Hypothyroidism • Homocysteinuria • G6PD deficiency • Hearing test Medical Conditions  of the Newborn Transient conditionsTransient conditions • Polycythemia • Tachypnea • Hyperbilirubinemia Delivery‐associated injuries Newborn infections Transient Conditions of the Newborn The Big Transient Three Polycythemia MTB S2CK  ‐ p. 406‐407  Hyperbilirubinemia Tachypnea Transient Polycythemia of the Newborn Source: James Van Rhee Polycythemia • Increased RBCs – Epo! • Primary vs. Secondary – Primary: Normal or low EPO levels MTB S2CK  ‐ p. 406 – Secondary: High EPO levels Polycythemia of the Newborn • Can be very harmful – Hyperviscosity, decreased perfusion, thromboses – LGA, SGA, and IDM Transient Polycythemia of the Newborn Transient Polycythemia • Benign • Most often related to cord clamping Hypoxia EPO! MTB S2CK  ‐ p. 406  4 Transient Tachypnea of the Newborn (TTN) Tachypnea • ≥ 60 BrPM (40 – 60 is normal) TTN or Respiratory Distress Syndrome II (RDS II) • Benign condition – 1% to 2% of newborns – Causes • Excess remaining lung fluid • Pulmonary immaturity • Surfactant deficiency/insufficiency – Management • Oxygen and antibiotics • Work-Up: CBC and chest radiograph MTB S2CK  ‐ p. 406‐407 Transient Tachypnea of the Newborn (TTN) The Takeaway: • Benign condition • Term infants • Delivered via C-section • Oxygen, antibiotics, and watch closely • Watch for  –Sepsis MTB S2CK  ‐ p. 406‐407 Transient Hyperbilirubinemia Hyperbilirubinemia • Production > Elimination  increased TSB – From increased production, decreased elimination, or both • Indirect = Unconjugated bilirubin • Direct = Conjugated bilirubinDirect Conjugated bilirubin – (Total Bili) – (Direct Bili) = Indirect Bili • Transient Hyperbilirubinemia – Benign and very common (~60% newborns) – Peaks at 2-3 days of life – Increased production of unconjugated bilirubin MTB S2CK  ‐ p. 407  Transient Hyperbilirubinemia • Any hyperbilirubinemia < 24 hr of life  –Evaluation • Any conjugated hyperbilirubinemia  –Evaluation MTB S2CK  ‐ p. 407  Transient Conditions of the Newborn The Big Transient Three Polycythemia MTB S2CK  ‐ p. 406‐407  Hyperbilirubinemia Tachypnea Types of injuries • Subconjunctival hemorrhage • Skull fracture • Scalp injuries • Brachial palsies Cl i l f t Delivery‐Associated Injuries • Microhemorrhages • Benign • Caput succedaneum • Cephalohematoma • Clavicular fracture • Facial nerve palsy MTB S2CK  ‐ p. 407  • Brief paralysis of facial nerve 5 Brachial Plexus Injuries General • Macrosomic infants (e.g., IDM) • Shoulder dystocia Duchenne-Erb Paralysis • 90% of brachial palsies C5 C6• C5 – C6 • “Waiter’s tip” • Cannot abduct or externally rotate Klumpke Paralysis • C7 – T1 • “Claw hand” +/- Horner syndrome MTB S2CK  ‐ p. 407‐408  Brachial Plexus Injuries    Clavicular Fracture • Most common newborn fracture • Usually result of: – Shoulder dystocia • Best diagnostic tool: – Radiograph MTB S2CK  ‐ p. 408  g p • Most appropriate management: – Immobilize Physical Exam • Physical exams start with vital signs... Age Group Heart Rate (HR) Respiration Rate (RR) Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP) Adult 60-100 BPM 16-24 BrPM 120 mmHg 80 mmHg Age Group Heart Rate (HR) Respiration Rate (RR) Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP) Adult 60-100 BPM 16-24 BrPM 120 mmHg 80 mmHg Age Group Heart Rate (HR) Respiration Rate (RR) Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP) Adult 60-100 BPM 16-24 BrPM 120 mmHg 80 mmHg Newborns 120-160 BPM 40-60 BrPM 65 mmHg 50 mmHgNewborns 120-160 BPM 40-60 BrPM 65 mmHg 50 mmHgNewborns 120-160 BPM 40-60 BrPM 65 mmHg 50 mmHg Neonatal Sepsis Early Late GBS E. Coli Listeria Staphylococci E. Coli GBS MTB S2CK  ‐ p. 433 Ampicillin Gentamicin Cefotaxime* Ampicillin Gentamicin Cefotaxime* IVF Cultures Antibiotics ToRCH Infections Type Presentation Diagnostic tests Treatment Toxo‐ plasmosis Chorioretinitis, hydrocephalus,  ring‐enhancing lesion Initial: IgM Most accurate: PCR Pyrimethamine and sulfadiazine Syphilis Rash on palms/soles, snuffles,  frontal bossing, Hutchinson 8th n. palsy, saddle nose Initial: VDRL / RPR Most accurate: FTA  ABS / Dark Field Penicillin ‐ IV PDA, cataracts, deafness,  hepatosplenomegaly, low plts, Elevated maternal  rubella IgM with SupportiveRubella MTB S2CK  ‐ p. 434 hepatosplenomegaly, low plts,  elevated bilirubins rubella IgM with clinical picture Periventricular calcifications,  microcephaly, chorioretinitis,  hearing loss Initial: Urine/saliva  viral titers Most accurate: PCR GanciclovirCMV Week 1: Shock and DIC Week 2: Vesicular skin lesions Week 3: Encephalitis Initial: Tzanck smear Most accurate: PCR Acyclovir and  supportive care Herpes 6 Common Abnormalities  of the Newborn Amniotic Fluid AbnormalitiesAmniotic Fluid Abnormalities Abdominal Abnormalities Genitourinary Abnormalities Amniotic Fluid Abnormalities Amniotic Fluid • 80% from mother • 20% from infant • Problems MTB S2CK  ‐ p. 408 –Polyhydramnios (too much) –Oligohydramnios (too little) Amniotic Fluid Abnormalities Polyhydramnios • Too much fluid • Overproduction / Decreased resorption • CNS malformations MTB S2CK  ‐ p. 408  Amniotic Fluid Abnormalities Polyhydramnios • GI malformations – Esophageal atresia MTB S2CK  ‐ p. 408  Amniotic Fluid Abnormalities Oligohydramnios • Too little fluid (Low AFI) • Under production • Causes – Post-term pregnancies Renal agenesis and renal failure MTB S2CK  ‐ p. 408 • ACE-inhibitors • Potter’s syndrome – Renal agenesis and renal failure • Cord Compression Abdominal Abnormalities A premature infant born at 28 weeks in respiratory distress with grunting, nasal flaring, and use of accessory muscles. Bowel sounds heard upon auscultation of the back and chest X-ray shows air fluid levels in the chest. Which of the following is the most likely diagnosis? a. Hydrocele b. Gastroschisis c. Diaphragmatic Hernia d. Hiatal Hernia e. Omphalocele MTB S2CK  ‐ p. 409  7 Abdominal Abnormalities MTB S2CK  ‐ p. 409  Source: Niket Sonpal, MD Abdominal Abnormalities Which of the following is the most likely diagnosis? a. Hydrocele b. Gastroschisis c. Diaphragmatic Hernia d Hi t l H i  M i GERD i d lt Abdominal wall defect Urological issue – not respiratory issue d. Hiatal Hernia e. Omphalocele MTB S2CK  ‐ p. 409  Abdominal wall defect More common in GERD – seen in adults Abdominal Abnormalities Diaphragmatic Hernia • Congenital defect in diaphragm • Two types: Bochdalek and Morgagni – LEFT side most common • Key findings: Respiratory distress MTB S2CK  ‐ p. 409 – Respiratory distress – Scaphoid abdomen – Bowel sounds in chest – Abnormal chest radiograph • First step in management… – Intubation Abdominal Abnormalities Omphalocele • Midline wall defect • With sac covering • Associations • Imperforate anus • Congenital heart defects (50%) Gastroschisis • Lateral wall defect • No sac covering • Atresias • Surgery is necessary • Conjoined twins  • Trisomy 18 (Edward’s  syndrome) • Beckwith‐Wiedemann syndrome • Surgery is necessary MTB S2CK  ‐ p. 410  Abdominal Abnormalities • An elevated AFP in abdominal wall defects • The MCC of elevated AFP is incorrect dating MTB S2CK  ‐ p. 410  • Umbilical hernias: Similar to omphaloceles Abdominal Abnormalities/Tumors Wilm’s Tumor • Most common primary renal malignancy in peds • Presents with… – Asymptomatic flank mass – Hematuria Hypertension and aniridia MTB S2CK  ‐ p. 410  – Hypertension and aniridia • First step in evaluation: Abdominal ultrasound • MC diagnostic test: Computed tomography • Relationships with syndromes – WAGR, Denys-Drash, Beckwith-Wiedemann • Treatment: Surgery + chemotherapy + radiation 8 Abdominal Abnormalities/Tumors Neuroblastoma • Very common among children • Often involves adrenal gland • Presents with… – Painful abdominal mass Neurological findings Neuroblastoma • Very common among children • Often involves adrenal gland • Presents with… – Painful abdominal mass Neurological findings MTB S2CK  ‐ p. 411 – Neurological findings • Opso(myo)clonus – Diarrhea • Diagnostic keys – Urine catecholamines and their metabolites • Vanillyl Mandelic Acid (VMA) – Neurological findings • Opso(myo)clonus – Diarrhea • Diagnostic keys – Urine catecholamines and their metabolites • Vanillyl Mandelic Acid (VMA) • Homovanillic acid (HVA) Genitourinary Abnormalities Hydrocele • Painless, benign, fluid-filled Cryptorchidism • Undescended testis, increased cancer risk • Surgical correction after 6 monthsSurgical correction after 6 months Hypospadias • Ventral surface opening, surgery Epispadias • Dorsal surface opening, surgery MTB S2CK  ‐ p. 411  Cyanotic Heart Defects Cyanotic Heart Defects • Tetralogy of Fallot • Transposition of the Great Vessels • Hypoplastic Left Heart Syndrome • Truncus Arteriosus • Total Anomalous Pulmonary Venous Return Tetralogy of Fallot The most common cyanotic heart defect in children • Four aspects p – Pulmonary stenosis – VSD – Overriding aorta – Right ventricular hypertrophy MTB S2CK  ‐ p. 412  Tetralogy of Fallot 9 Tetralogy of Fallot/Signs & Symptoms Cyanosis • Lips and extremities Squatting • Increases systemic pressure • Shunts blood to pulmonary circulation H l t li MTB S2CK  ‐ p. 412‐413  • Holosystolic murmur • VSD There are 3 holosystolic murmurs • Mitral regurgitation (MR) • Tricuspid regurgitation (TR) • Ventricular septal defect (VSD) Tetralogy of Fallot Tetralogy of Fallot Transposition of the Great Vessels Two separate circulations • Right heart/systemic circulation • Left heart/pulmonary circulation Defect dependent • Patent ductus arteriosus (PDA) MTB S2CK  ‐ p. 413  Patent ductus arteriosus (PDA) • VSD • Atrial septal defect (ASD) Most common cyanotic lesion of neonates Transposition of the Great Vessels Transposition of the Great Vessels Treatment • Prostaglandin E1 • Surgery MTB S2CK  ‐ p. 413  10 Hypoplastic Left Heart Syndrome Syndrome • Absent pulses • Right ventricular heave • Mild cyanosis/gray MTB S2CK  ‐ p. 414  Hypoplastic Left Heart Syndrome Truncus Arteriosus • One Great Vessel • The less common heart defect (2%) • NOT dependent on PDA • Mild cyanosis • Big problem: Pulmonary hypertension • Treat with… –Surgery! MTB S2CK  ‐ p. 414  Truncus Arteriosus Total Anomalous Pulmonary Venous Return • Abnormal pulmonary venous return –Pulmonary veins  Right atrium • PFO dependent • Right heart overload • Two types: –With obstruction –Without obstruction MTB S2CK  ‐ p. 414‐415 TAPVR ‐ 2 Sign/Symptoms Tests Treatment TAPVR with obstruction Early in life with  respiratory  distress and  severe cyanosis CXR shows  pulmonary  edema Echo is test of  choice Surgery S MTB S2CK  ‐ p. 415  TAPVR without obstruction Presents later Age 1‐2 years  with heart  failure CXR shows  “snowman” sign Echo is test of  choice Surgery 11 Cyanotic Heart Defects R  L Shunt T G V T O F Hypoplastic LH PDA dep VSD   Surgery       TAPVR Truncus Art   Acyanotic Heart Defects Acyanotic Heart Defects • VSD • ASD PDA• PDA • Coarctation of the aorta 3-year old female brought in because her parents say she won’t eat anymore. Upon physical examination, a loud pansystolic murmur is appreciated. The child appears small for her age, but her records don’t show any maternal or delivery complications. Which of the following is the most likely finding on EKG? Heart murmur in a child MTB S2CK  ‐ p. 415 a. Right ventricular hypertrophy b. RBBB c. ST-segment elevation d. QT-prolongation e. P-wave inversion Ventricular Septal Defect There are 3 holosystolic murmurs... • MR • TR • VSD VSD is the most common congenital heart defect MTB S2CK  ‐ p. 415 VSD, Murmurs, and Auscultation VSD 12 Ventricular Septal Defect • Pathophysiology – Left-to-Right shunt (opposite of cyanotic defects) – Pulmonary hypertension • Presentation – Dyspnea with distress – Loud pulmonic S2 MTB S2CK  ‐ p. 416 – High-pitched holosystolic murmur • Tests – CXR: Findings are not diagnostically helpful – Best initial test is an echocardiogram – Most diagnostic (definitive) test is a cardiac catheterization Ventricular Septal Defect 3-year old female brought in because her parents say she won’t eat anymore. Upon physical examination, a loud pansystolic murmur is appreciated. The child appears small for her age, but her records don’t show any maternal or delivery complications. Which of the following is the most likely finding on EKG? Heart murmur in a child MTB S2CK  ‐ p. 415 a. Right ventricular hypertrophy b. RBBB c. ST-segment elevation d. QT-prolongation e. P-wave inversion VSD VSD & Eisenmenger Syndrome  3-year old female brought in because her parents say she won’t eat anymore. Upon physical examination, a loud pansystolic murmur is appreciated. The child appears small for her age, but her records don’t show any maternal or delivery complications. Which of the following is the most likely finding on EKG? MTB S2CK  ‐ p. 415  ASD or ischemic disease Myocardial infarction Electrolyte disturbances Atrial arrhythmias a. Right ventricular hypertrophy b. RBBB c. ST-segment elevation d. QT-prolongation e. P-wave inversion 13 Atrial Septal Defect vs. Physiologic splitting • Types of ASDs – Primum, secundum, and sinus venosus – 2xs common in men • Usually asymptomatic • Fixed wide-splitting S2 • Tests MTB S2CK  ‐ p. 416‐417 • Tests – Best initial test is an echocardiogram (bubble study) – Most diagnostic test is a cardiac catheterization • Prognosis – Most close without intervention Atrial Septal Defect • Without closure… – Atrial enlargement – Dysrhythmias – Embolic Risk • Treatment – Surgical Atrial Septal Defect Surgical Patent Ductus Arteriosus • Failure of closure after 12 hours • Left-to-Right shunt • Presentation – Machinery-like murmur – Wide pulse pressures Bounding pulses– Bounding pulses • Tests – Best initial test is an echocardiogram – Most diagnostic test is a cardiac catheterization • Treatment – NSAIDS (indomethacin) MTB S2CK  ‐ p. 417 Patent Ductus Arteriosus Patent Ductus Arteriosus 14 Coarctation of the Aorta • Congenital narrowing of aorta – Usually after cephalic branches • Turner’s Syndrome • Presentation – Differential blood pressure • Between upper and lower body MTB S2CK  ‐ p. 418‐419 • Between upper and lower body • “Hypertension” – CHF and respiratory distress • Tests – Best initial tests are an echo or CXR – Most diagnostic test is a cardiac catheterization Coarctation of the Aorta Gastroenterology – Part 2 Volvulus & Intussusception Meckel’s Diverticulum Diarrhea & Gastroenteritis Volvulus • What is it? – Malrotation of gut • What causes it? – Non-rotation during development • How does it present? • How is it managed? – Decompression of gut + IVF – Surgery • If decompensating... – Proceed immediately How does it present? – 90% within first year of life – Bilious vomiting – “Colicky” abdominal pain y to OR – Get antibiotics on board MTB S2CK  ‐ p. 424‐425 Intussusception • “Telescoping bowel” • Presentation – Colicky abdominal pain – Bilious vomiting – “Currant-jelly” stool – “Sausage-like” mass This triad is commonly used on S2! Sausage-like mass • First steps in management: – IVF and correction of electrolytes – NG tube for decompression MTB S2CK  ‐ p. 425‐426 • Testing and Treatment – Best initial test: Ultrasound – Air contrast/barium enema • Diagnostic and therapeutic – Signs of peritonitis/perforation  Surgery Intussusception Source: Brad L. KocherSu ge y – Recurrence ~10% MTB S2CK  ‐ p. 426 Source: Boma O. Afiesimama 15 Bilious Vomiting Bilious Vomiting Duodenal Atresia Volvulus Intussusception • Within 1st year • Initial test: • Within 1st day • Initial test: • Within 1st year • Initial test: MTB S2CK  ‐ p. 424 ‐ 426 • AXR • First Step • IVF! • Treament • Surgery • AXR • “Double bubble” • First Step • IVF! • Treament • Surgery • US • “Doughnut” • First Step: • IVF! • Treatment • Air Enema Meckel’s Diverticulum • Rule of 2’s • 2% prevalence • ≤ 2 years old • 2 ft proximal to ileocecal valve • 2 inches long • 2 types of ectopic tissue MTB S2CK  ‐ p. 426‐427 • 2 types of ectopic tissue • Males 2x more affected • 2% symptomatic Painless rectal bleeding © Katsumi M. Miyai, M.D., Ph.D., Regents of the University of California. Used with permission. Diarrhea and Gastroenteritis The most important questions to ask: • Is this chronic or acute? • Infectious or not? • Bloody or not? • How sick is the child? MTB S2CK  ‐ p. 427 Diarrhea and Gastroenteritis Infectious Diarrhea Viral BacterialParasites Fungal • Salmonella • Shigella • C difficile • Candida spp • Histoplasma • Giardia • Cryptosporidia • C. difficile • E. Coli • Campylobacter • Yersinia Diarrhea and Gastroenteritis Infectious Diarrhea Viral Rotavirus M t Adenovirus Small, round E d i N lk• Most common • Winter • Symptoms: • Fever, emesis • NO blood •  7 days • Viral prodrome • Norwalk • EPI‐demic • Symptoms: • Explosive • Cramping, pain • Short‐lived • 1‐2 days Diarrhea and Gastroenteritis Management • Hydration is key –Almost always the answer • Antibiotics for suspected bacterial i f tiinfection –WBC or blood in stool –NEVER use antidiarrheal meds in these patients MTB S2CK  ‐ p. 428 16 Endocrinology Infants of Diabetic Mothers Congenital Adrenal Hyperplasia (CAH)g yp p ( ) Vitamin D Deficiencies Large for Gestational Age/Macrosomia A 10.5-pound infant is born to a mother with Type I diabetes. Upon examination of newborn, he is shaking, and a holosystolic murmur is heard over precordium. The baby’s right arm is adducted and internally rotated. His lab findings show an elevated bilirubin. Which of the following is the most appropriate next step in management? a. IV insulin MTB S2CK  ‐ p. 429 a. IV insulin b. Blood sugar level c. Serum calcium levels d. Serum TSH e. CT head and neck Infants of Diabetic Mothers (IDM) Maternal Hyperglycemia Fetal / Infant Hyperglycemia Infant Hyperinsulinemia MTB S2CK  ‐ p. 430 Infants of Diabetic Mothers (IDM) • Four primary issues... – Macrosomia – Hypoglycemia – Electrolyte abnormalities – JaundiceJaundice MTB S2CK  ‐ p. 430 IDM/Macrosomia • “Macrosomia” = weight ≥ 4500 g • “Large for gestational age” (LGA) = top 90th percentile • Causes in IDM – Oversupply of AA’s, glucose, etc. – Insulin is a growth factor C• Consequences – Trauma – Risk of C-section • Treatment – None… Prevention! MTB S2CK  ‐ p. 430 IDM/Hypoglycemia Maternal Hyperglycemia Infant Hyperglycemia Infant Hyperinsulinemia MTB S2CK  ‐ p. 430 Birth 17 IDM/Hypoglycemia • Direct consequence of maternal hyperglycemia • Hypertrophied pancreatic beta-cells – Insulin overproduction – Hyperresponsive • After birth: N h i i li d ti / ti it MTB S2CK  ‐ p. 430 – No changes in insulin production/activity • Consequences – Severe hypoglycemia – Seizures • Treatment – Monitoring + Glucose IDM/Electroyte abnormalities • Hypocalcemia – Hypomagnesemia / Hyperphosphotemia • Twitching and Tremulousness • Cardiac arrhythmias • Calcium and Magnesium levels linked Al h k b th– Always check both – Correct together MTB S2CK  ‐ p. 430 IDM/Jaundice • One-third of IDM’s will develop jaundice • Unconjugated/Indirect hyperbilirubinemia • Overproduction of bilirubin – Resolving hematomas – Polycythemia T t t• Treatment – Phototherapy MTB S2CK  ‐ p. 430 IDMs have hyperinsulinemia A 10.5-pound infant is born to a mother with Type I diabetes. Upon examination of newborn, he is shaking, and a holosystolic murmur is heard over precordium. The baby’s right arm is adducted and internally rotated. His lab findings show an elevated bilirubin. Which of the following is the most appropriate next step in management? a. IV insulin MTB S2CK  ‐ p. 429  Check, but not most immed. Good test, but not relevant No concern trauma or bleed a. IV insulin b. Blood sugar level c. Serum calcium levels d. Serum TSH e. CT head and neck IDM/Other • Other abnormalities – Small left colon syndrome – Respiratory distress syndrome (RDS) – Cardiac abnormalities MTB S2CK  ‐ p. 430 Congenital Adrenal Hyperplasia (CAH) Cholesterol 17-OH- Pregnenolone Pregnenolone 17-OH- Progesterone Deoxycortisol Cortisol g DHEA Androstenediol Androstenedione Testosterone Estradiol Estrone 17α-hydroxylase deficiency 21-hydroxylase deficiency 11β-hydroxylase deficiency 18 CAH: 17α‐Hydroxylase Deficiency Cholesterol Cortisol Aldosterone MTB S2CK  ‐ p. 430 Testosterone Estradiol 17α-hydroxylase deficiency Congenital Adrenal Hyperplasia 17α‐hydroxylase def 21‐hyroxylase def 11β‐hydroxylase def Classic S2CK: teenage girl presents with delayed puberty and incidentally found to have • Aldosterone • Cortisol • Sex hormones • HYPERtensive • Sex Development MTB S2CK  ‐ p. 430 elevated BP p • Girls: nml at birth • Boys: pseudo‐ hermaphroditism • Electrolytes • Hypokalemia 21‐Hydroxylase Deficiency Cholesterol Cortisol Aldosterone MTB S2CK  ‐ p. 430 Testosterone Estradiol 21-hydroxylase deficiency Congenital Adrenal Hyperplasia 17α‐hydroxylase def 21‐hyroxylase def • Aldosterone • Cortisol • Sex hormones • HYPOtensive • Salt‐wasting Shock 11β‐hydroxylase def • Aldosterone • Cortisol • Sex hormones • HYPERtensive • Sex Development MTB S2CK  ‐ p. 430 • Sex Development • Girls: virilized • Boys: nml at birth • Electrolytes • Hyponatremia • Hypochloremia • Hyperkalemia p • Girls: nml at birth • Boys: pseudo‐ hermaphroditism • Electrolytes • Hypokalemia 11β‐Hydroxylase Deficiency Cholesterol Cortisol Aldosterone 11-DOC MTB S2CK  ‐ p. 430 Testosterone Estradiol 11β-hydroxylase deficiency Congenital Adrenal Hyperplasia 17α‐hydroxylase def 21‐hyroxylase def • Aldosterone • Cortisol • Sex hormones • HYPOtensive • Salt‐wasting Shock 11β‐hydroxylase def • Aldosterone • Cortisol • Sex hormones • 11‐DOC • HYPERtensive • Aldosterone • Cortisol • Sex hormones • HYPERtensive • Sex Development MTB S2CK  ‐ p. 430 • Sex Development • Girls: virilized • Boys: nml at birth • Electrolytes • Hyponatremia • Hypochloremia • Hyperkalemia • Sex Development • Girls: virilized • Boys: nml at birth • Few electrolytes abnormalities p • Girls: nml at birth • Boys: pseudo‐ hermaphroditism • Electrolytes • Hypokalemia 19 Congenital Adrenal Hyperplasia Cholesterol 17-OH- Pregnenolone Pregnenolone 17-OH- Progesterone Deoxycortisol Cortisol g DHEA Androstenediol Androstenedione Testosterone Estradiol Estrone 17α-hydroxylase deficiency 21-hydroxylase deficiency 11β-hydroxylase deficiency Rickets • Disorder of children – Soft and weak bones  fractures • Vitamin D, calcium, and phosphate • Children are particularly susceptible – Rapidly growing bones B t ilk d fi i i it i D– Breast milk deficiency in vitamin D • Prophylaxis with vitamin D supplements Rickets Bone Metabolism/Simplified Vitamin D PTH Calcium Phosphate Bone Metabolism/Simplified Vitamin D PTH Calcium Phosphate Rickets MTB S2CK  ‐ p. 432 Source: Paul M Michaud 20 Rickets • Disorder of children – Soft and weak bones  fractures • Vitamin D, calcium, and phosphate • Children are particularly susceptible – Rapidly growing bones B t ilk d fi i i it i D– Breast milk deficiency in vitamin D • Prophylaxis with vitamin D supplements • Treat with vitamin D and calcium supplements MTB S2CK  ‐ p. 431 Pulmonary Croup Epiglottitisp g Whooping Cough Asthma  Croup 2-year-old brought in by daycare provider for severe cough, fever, and runny nose. The child’s cough sounds like a bark and she’s in obvious respiratory distress. Upon physical examination, the child refuses to lie flat. A chest X-ray shows a positive steeple sign. What is the most appropriate next step in management? MTB S2CK  ‐ p.435 Not necessary in croup Not first step in improving airway Not first step in improving airway Not first step in improving airway a. Intubate b. Racemic epinephrine c. Empiric antibiotics d. Acetaminophen e. CT-scan of neck Anatomy of upper airway disease commons.wikimedia.org. Used with permission Croup Croup • Laryngotracheitis or Laryngotracheobronchitis • Infection of upper airway – Subglottic space • Viral – Parainfluenza or RSV • Treatment – Moderate severity: Steroids – Severe: Racemic epinephrine and steroids Parainfluenza or RSV • Presentation – Triad: barking cough, coryza, and stridor – Respiratory distress: accessory muscle use – CXR: Steeple sign MTB S2CK  ‐ p. 435 Think bacterial causes: (1) older kids or (2) those unresponsive to racemic epinephrine The MOST common cause of stridor in children  4-year-old child brought in by daycare provider because he’s extremely irritable and refuses to eat. He refuses to lean back, speaks in muffled words, looks extremely ill, and is drooling. Chest radiograph shows a positive thumb-print sign. What is the most appropriate next step in management? a. Intubate Epiglottitis MTB S2CK  ‐ p. 436 Only for croup Good – not most immeidate Fever is not a concern Further imaging not warranted b. Racemic epinephrine c. Empiric antibiotics d. Acetaminophen e. CT-scan of the neck 21 Anatomy of upper airway disease commons.wikimedia.org. Used with permission Croup Epiglottitis Epiglottitis • Upper-airway infection and emergency • MCC: Bacterial – Non-vaccinated: H. influenzae type-B – Vaccinated: Streptococcus species and nontypeable H. influenzae • Presentation F d li i t di t– Fever, drooling, respiratory distress – NO coryza, NO prodrome, NO cough • Management – Transfer to O.R.  INTUBATE – Start empiric antibiotics: ceftriaxone or cefuroxime – No imaging required MTB S2CK  ‐ p. 436 Epiglottitis Source: MS-4 USU • Bordetella pertussis  “Whooping Cough” – Gram-negative, non-invasive – Causes ciliary paralysis • Three Stages: Pertussis MTB S2CK  ‐ p. 437 Pertussis/Stages Catarrhal Paroxysmal Convalescent ~ 14 days 14 – 30 days ~ 14 days •Rhinorrhea, congestion, “cold sx’s” •Severe coughing •Post-tussive emesis •Prolonged resolution of symptoms MTB S2CK  ‐ p. 437 cold sx s •Most contagious time period •Only time abx helpful to patient •Usually no fever •Low requirement for admission •Abx prescribed to reduce transmissibility symptoms •Coughing fits remain – less respiratory distress Pertussis • Bordetella pertussis  “Whooping Cough” – Gram-negative, noninvasive – Causes ciliary paralysis • Three Stages: – Catarrhal Stage: 14 days R ti “URI S t ” MTB S2CK  ‐ p. 437 • Runny nose, congestion, “URI Symptoms” • Most contagious time period – Paroxysmal Stage: 14-30 days • Severe coughing, posttussive emesis – Convalescent Stage: 14 days • Resolution of symptoms 22 Pertussis • Diagnosis – This is a clinical diagnosis – CXR is helpful – PCR useful where available • Management P ti t P i il ti– Patient: Primarily supportive • Catarrhal stage – azithromycin/erythromycin • Everybody gets treated – Close contacts: Macrolides – The community: Vaccination campaigns MTB S2CK  ‐ p. 437 Viral Infections of Childhood Virus Presentation Diagnostic tests Treatment Varicella Multiple highly pruritic  vesicular rash; starts on face;  fever/malaise Initial: Tzanck smear Most accurate:  culture Supportive Rubeola (Measles) Cough, Coryza, and  Conjunctivitis; Koplik spots Initial: Clinical Most accurate: IgM Supportive Fever and URI symptoms;  “ l d h k ” h Clinical diagnosis SupportiveFifth’s  d MTB S2CK  ‐ p. 434 “slapped cheeks” rashdisease Fever and URI progressing  to diffuse rash Clinical diagnosis SupportiveRoseola Fever precedes classic  parotid gland swelling with  possible orchitis Clinical diagnosis SupportiveMumps Asthma • The most common chronic disease in children • Pathophysiology – Reversible obstruction – Hyperresponsiveness – Inflammation • Remodeling • Diagnosis – No single available test – Clinical – Pulmonary Function Tests (PFTs) – Bronchoprovocation – CXR MTB S2CK  ‐ p. 129‐130 Decreased FEV1 and FEV1/FVC ratio! Asthma • Treatment – Avoidance of triggers – Short-acting ß2-agonists (SABA) – Inhaled corticosteroids (ICS) – Long-acting ß2-agonists (LABA) L k t i t i t ( difi ) (LTRA)– Leukotriene antagonists (modifiers) (LTRA) MTB S2CK  ‐ p. 131‐132 Asthma/Treatment ADD LABA, LTRA or High-dose ICS and LABA High-dose ICS and LABA and Oral MTB S2CK  ‐ p. 131‐132 Severity of Symptoms SABA as needed ADD Low-dose ICS LTRA, or move to medium- dose ICS LABA Oral steroids 1 Psychiatry Sam Asgarian, MD/MBA Class of 2012 Tulane University Childhood Disorders Mental Retardation Pervasive Developmental Disorders  Attention Deficit Hyperactivity Disorder  Tourette Disorder  Mental Retardation  To determine the level of retardation patients must exhibit deficits in both • Intellectual functioning – Cognitive abilities • Social adaptive functioning – Perform daily activitiesPerform daily activities More frequent in boys • Highest incidence being in school-age children MTB S2CK  ‐ p. 503 Types of Mental Retardation Mild  • IQ range – 50–55 to 70 • Level of functioning – 6th grade level – Can work and live Moderate  • IQ range – 30–40 to 50–55 • Level of functioning – 2nd grade level – May work with independently – Needs help in difficult or stressful situations supervision and support – Needs help in mildly stressful situations MTB S2CK  ‐ p. 503 Types of Mental Retardation Severe  • IQ range – 20–25 to 35–40 • Level of functioning – Little or no speech, very limited abilities to Profound  • IQ range – < 20 • Level of functioning – Needs continuous care and supervision y manage self care p MTB S2CK  ‐ p. 503 Mental Retardation/Treatment  Treatment • Genetic counseling, prenatal care, and safe environments for expectant mothers • If due to medical condition (e.g., PKU) treat disorder • Special education to improve level of functioningSpecial education to improve level of functioning • Behavioral therapy to reduce negative behaviors MTB S2CK  ‐ p. 503‐504 2 Pervasive Developmental Disorders/Definition  Characterized by • Social, behavioral, and language problems – Occurs before age 3 Childhood Developmental Disorders Autistic disorder• Autistic disorder • Rett disorder • Childhood disintegrative disorder • Asperger disorder MTB S2CK  ‐ p. 504 Autistic Disorder • Incidence: boys > girls • Lacks peer relationships, poor eye contact, and social smile • Absent or bizarre speech • Repetitive behaviors – Stacking – Injurious behavior to self or others MTB S2CK  ‐ p. 504 ~18 mo boy with autism, obsessively stacking cans Source: Andwhatsnext , commons.wikimedia.org Autistic Treatment • Improve ability to develop relationships, attend school, and achieve independent living • May benefit from behavioral modification programs • If aggressive, use antipsychotic medications MTB S2CK  ‐ p. 504 Rett disorder  • Greater incidence in girls • Progressive encephalopathy • Microcephaly • Hand-wringing • Loss of speech At i• Ataxia • Psychomotor retardation Treatment • Symptomatic • Behavior therapy for self-injurious behavior • Physiotherapy for muscular dysfunction MTB S2CK  ‐ p. 504 Childhood Disintegrative Disorder • Greater incidence in boys • Normal development for 2 years, followed by marked functional regression in – Loss of language – Social interactionSocial interaction – Motor function – Bladder function • Repetitive/stereotyped behaviors MTB S2CK  ‐ p. 504 Childhood Disintegrative Disorder/Treatment • Improve ability to develop relationships, attend school, and achieve independent living • May benefit from behavioral modification programsmodification programs • If aggressive, use antipsychotic medications MTB S2CK  ‐ p. 504 3 Asperger Disorder  • Greater incidence in boys • Social and behavioral problems • No language or intellectual deficits • Preoccupied with rules MTB S2CK  ‐ p. 504 Often display intense interests. Source: Poindexter Propellerhead at the English language, commons.wikimedia.org Treatment • Improve relationships with others Gabriel is a healthy 2-year-old boy whose parents have taken him to the pediatrician. His problems started at 18 months of age, when he did not speak much. He does not have much attachment to his parents and seems aggressive toward other children. What is the most likely diagnosis? MTB S2CK  ‐ p. 504‐505  Ruled out Impaired judgment, behavior, and reality Progressive encephalopathy, loss of speech, ataxia, and psychomotor retardation No evidence of learning deficit a. Deafness b. Schizophrenia, childhood onset c. Rett disorder d. Autism e. Learning deficit Attention‐Deficit Hyperactivity Disorder Characterized by • Inattention • Short attention span Or • Hyperactivity that interferes with dailyinterferes with daily functioning in school, home, or work • Must be present for > 6 months and usually appears before age 7 • The symptoms may persist into adulthood MTB S2CK  ‐ p. 505 Source: cdc.gov ADHD Symptoms must be present in at least 2 areas, such as: • Home – Interrupt others – Fidget in chairs – Run or climb excessively • School – Unable to pay attention – Make careless mistakes in y – Unable to engage in leisure activities – Talk excessively schoolwork – Do not follow through with instructions – Difficulties organizing tasks – Easily distracted MTB S2CK  ‐ p. 505 Treatment • First-line: methylphenidate and dextroamphetamine – Side effects: insomnia, decreased appetite, and headache • Second-line: atomoxetine (norepinephrine reuptake inhibitor) • On the USMLE Step 2 CK, atomoxetine is usually chosen over the first-line treatment, given the side effect profiles of those treatments MTB S2CK  ‐ p. 505 Disruptive Behavioral Disorders Oppositional Defiant Disorder Epidemiology • Usually noted by age 8 • Boys > girls before puberty –But equal incidence after puberty MTB S2CK  ‐ p. 506 4 Disruptive Behavioral Disorders/ Oppositional Defiant Disorder Features • Argues often • Loses temper • Easily annoyed • Blames others for • Justifies behavior as response to others’ actions • Blames others for their mistakes • Tends to have problems with authority figures MTB S2CK  ‐ p. 506 Source: Chris Willia, commons.wikimedia.org Disruptive Behavioral Disorders/ Oppositional Defiant Disorder Treatment • Teach parents appropriate child management skills and how to lessen iti l b h ioppositional behavior MTB S2CK  ‐ p. 506 Disruptive Behavioral Disorders Conduct Disorder Epidemiology • Seen more frequently in –Boys whose parents have antisocial personality disorder and alcoholpersonality disorder and alcohol dependence MTB S2CK  ‐ p. 506 Disruptive Behavioral Disorders/ Conduct Disorder Features • Persistent behavior where rules are broken • Behaviors include aggression toward others: – Bullying Cruelty to animals– Cruelty to animals – Fighting Or – Using weapons • Vandalize and destroy property; set fires • Steal items from others or lie to obtain goods from others • Violate rules (truancy, running away from home, breaking curfew) MTB S2CK  ‐ p. 506 Source: Diego Grez, commons.wikimedia.org Disruptive Behavioral Disorders/ Conduct Disorder Treatment • Behavioral intervention using rewards for prosocial and nonaggressive behavior • If aggressive –Antipsychotic medications have been used MTB S2CK  ‐ p. 506 A 10-year-old boy is seen by the school counselor after teachers complained of his behavior. He frequently becomes angry toward others and loses his temper. His parents report that he refuses to comply with house rules, stays up past his bedtime, and frequently talks back to them. What is the most likely diagnosis? a. Conduct disorder Breaks rules of society or commits crimes b. Tourette disorder c. Adjustment disorder d. Oppositional Defiant Disorder e. Learning disorder, not otherwise specified MTB S2CK  ‐ p. 506  crimes Multiple tics Maladaptive reaction to identifiable stressor Needs evidence of a learning problem 5 Tourette Disorder • Characterized by onset of multiple tics – Lasting > 1 yr – Occurs before age 18 • Motor tics most commonly involve – Facial and neck muscles (e.g., head shaking and blinking) • The vocal tics include – Grunting, coughing, and throat clearing MTB S2CK  ‐ p. 506 Tourette Disorder/Treatment  • Seen more frequently in – Boys – Begins at age 7 • Dopamine antagonistsp g – Antipsychotic medications (e.g., risperidone) MTB S2CK  ‐ p. 507 Psychiatry Sam Asgarian, MD/MBA Class of 2012 Tulane University Mood Disorders  Major Depression  Bipolar Disorder DysthymiaDysthymia  Cyclothymia Atypical Depression Seasonal Affective Disorder  Bereavement (Grief)  Major Depression • Mood disorders present with at least a 2-week course of symptoms that’s a change from the previous level of functioning Vincent van Gogh's 1890 painting Sorrowing old man ('At Eternity's Gate') Source: The Yorck Project, commons.wikimedia.org MTB S2CK  ‐ p. 507 Major Depression Symptoms • Depressed mood or anhedonia (absence of pleasure) And • 4 others including Depressed mood most Fatigue– Depressed mood most of day – Weight changes – Sleep changes – Psychomotor disturbances MTB S2CK  ‐ p. 507 – Fatigue – Poor concentration – Thoughts of death and worthlessness 6 Major Depression/Diagnosis and Treatment  Diagnosis • Rule out medical causes – Most common (hypothyroidism) • Most common neurological associations are – Parkinson disease and dementia First-line treatment: SSRIs • Fluoxetine • Paroxetine • Sertraline • Citalopram • Escitalopram MTB S2CK  ‐ p. 507 Major Depression/Treatment  • SSRIs – Effective and relatively mild side effects – Less toxic in overdose than other antidepressants • If some improvement, but not full response – Increase dose of SSRI • Psychotherapy (e.g., cognitive therapy) proven to bePsychotherapy (e.g., cognitive therapy) proven to be effective • Goal of cognitive therapy is – Reduce depression by teaching patients to identify negative cognitions and develop positive ways of thinking MTB S2CK  ‐ p. 507 Major Depression  SSRIs should NOT be taken with MAO inhibitors as they will cause a dramatic increase in serotonin. • USMLE Step 2 CK won’t give you 2 SSRIs from which to choose MTB S2CK  ‐ p. 507‐508 Exceptions to SSRI Use Variety of depression  Specific alternative to SSRIs Patient with depression and  neuropathic pain  Patient with depression who  i f f l f i h i Use desvenlafaxine Approved for both  depression & neuropathy Bupropion has fewer  l id ff d l MTB S2CK  ‐ p. 507 is fearful of weight gain or  sexual side effects sexual side effects and less  weight gain than SSRIs Also used as adjunct  treatment for SSRI‐ induced sexual side effects 45-year-old woman was seen by her PCP due to complaints of depressed mood, lack of pleasure, sleep problems, decreased appetite and weight, decreased energy, and problems with concentration. She states that these symptoms started when she was fired from her job about 4 weeks ago, and that since then, she has been unable to function. What is the most indicated treatment at this time? a. Alprazolam b. Paroxetine c. Bupropion d. Venlafaxine e. Trazodone f. Electroconvulsive therapy MTB S2CK  ‐ p. 508  Anxiolytic Not 1st line When initial therapy doesn’t work, or depression more severe and associated with psychotic features Major Depression  Choices on USMLE may include an SSRI and another antidepressant medication Pick the cleanest: SSRI MTB S2CK  ‐ p. 508 7 Bipolar Disorder  • Mood disorder • Patient experiences – Manic symptoms that last at least 1 week – Cause significant distress in level of functioning MTB S2CK  ‐ p. 508 Source: commons.wikimedia.org Bipolar Disorder  Manic symptoms • Elevated mood • Increased self-esteem • Distractibility • Pressured speech • Decreased need for • Increase in goal- directed activity • Racing thoughts • Excessive involvement in pleasurable • Decreased need for sleep p activities MTB S2CK  ‐ p. 508Source: commons.wikimedia.org Source: commons.wikimedia.org Bipolar Disorder • Typically starts with depression Diagnosis • Exclude drug use – Cocaine/amphetamineCocaine/amphetamine • Obtain history and urine drug screen MTB S2CK  ‐ p. 508 Bipolar Disorder  M i H i The difference between mania and hypomania • Severity of symptoms • Level of functioning • Duration • Mania – > 1 week – Affect functioning – Warrant hospitalization • Hypomania – < 1week – Don’t severely affect functioning – Don’t warrant hospitalization MTB S2CK  ‐ p. 508 Types of Bipolar Disorders Bipolar disorder type I Mania and depression Bipolar disorder type II Hypomania and depression MTB S2CK  ‐ p. 509 21-year-old college student was taken to the university clinic after she was noted to be acting bizarrely in class. She is talking fast and reported that she has not slept for over 4 days. She appears to be giggling and not paying attention in class. Her roommate reported that she has been drinking alcohol excessively over the last few days and has had many sexual contacts with unknown men. Wh t i th t lik l di i ?What is the most likely diagnosis? a. Alcohol-induced mood disorder b. Bipolar disorder type I c. Bipolar disorder type II d. Major depression with psychosis e. Cyclothymia MTB S2CK  ‐ p. 509  Hypomania No history of alcoholism Thoughts of death, preoccupation with worthlessness, psychomotor retardation, psychosis Hypomanic episodes and mild depression 8 Bipolar Disorder/Treatment Bipolar depression You must distinguish whether Acute mania 1st line • LithiumSevere MTB S2CK  ‐ p. 509 • Lithium • Valproic acid • Atypical antipsychotics • Lamotrigine symptoms, consider Atypical antipsychotics • Shorter onset of action Bipolar Disorder  • If kidneys are compromised, don’t use lithium Lithi i th t t t• Lithium is the correct answer to most bipolar questions MTB S2CK  ‐ p. 509 33-year-old man was taken to emergency room by police after neighbors complained about his behavior. His family informed the doctor he’s been diagnosed with bipolar disorder and was recently started on lithium. While in the emergency room, he became combative and punched a nurse on the mouth. What is the next step in the management of this patient? a. Obtain lithium level Symptoms are acute b. Admit to psychiatric unit c. Refer to psychiatry d. Add valproic acid e. Olanzapine MTB S2CK  ‐ p. 509‐510  Never refer > important to treat 1st line is an antipsychotic Dysthymia  Characterized by • Depressed mood that lasts most of the day and is present almost continuously • Symptoms must be present for: > 2 years • Treatment –Antidepressant medications and psychotherapy MTB S2CK  ‐ p. 510 Cyclothymia Characterized by • Hypomanic episodes and mild depression • Symptoms must be present for: > 2 years • Treatment – Lithium, valproic acid, or carbamazepine – Psychotherapy MTB S2CK  ‐ p. 510 Atypical Depression  Characterized by • Reverse vegetative changes –Increased sleep –Increased weight Increased appetite–Increased appetite • Mood tends to be worse in evenings and patients may complain of extremities feeling “heavy” MTB S2CK  ‐ p. 510 9 Atypical Depression/Treatment  • SSRIs or MAOIs • SSRIs have better side-effect profile • If MAOIs and SSRIs are in the same question, choose SSRIs because of side- effect profile Usually MAOIs are answer on Step 2 for atypical depression MTB S2CK  ‐ p. 510 Seasonal Affective Disorder  Characterized by • Seasonal changes in mood during fall and winter • Symptoms – Weight gain Increased sleep– Increased sleep – Lethargy • Treat with – Phototherapy and bupropion MTB S2CK  ‐ p. 510 Postpartum Disorders Disorder  Postpartum blues or “baby blues” Onset Symptoms Mother’s feelings toward baby Treatment Immediately after birth up to 2 weeks Sadness, labile mood, tearfulness No negative feelings Supportive, usually self‐limited  MTB S2CK  ‐ p. 511 Source: commons.wikimedia.org Postpartum Disorders Disorder  Postpartum depression Onset Symptoms Mother’s feelings  toward baby Treatment Within 1–3 months after birth Depressed mood, weight changes, sleep  disturbances, and excessive anxiety May have negative feelings toward baby Antidepressant medications  MTB S2CK  ‐ p. 511 Source: commons.wikimedia.org Postpartum Disorders Disorder  Postpartum psychosis Onset Symptoms Mother’s feelings toward baby Treatment Within 2–3 weeks after birth Depression, delusions, and thoughts  of harm May have thoughts of harming baby Antipsychotic medication, lithium,  and possibly antidepressants  MTB S2CK  ‐ p. 511 Source: commons.wikimedia.org Bereavement (Grief) Bereavement Major depression  (greater severity than bereavement)  Begins after death of  loved one  Feelings of •Sadness  •Worrying  Thoughts of death Morbid preoccupation with  worthlessness Marked psychomotor  retardation  MTB S2CK  ‐ p. 511 y g •Irritability  •Sleep difficulties  •Poor concentration  •Tearfulness   2 months and adversely  affect functioning  10 Bereavement (Grief) • Treatment – Supportive psychotherapy • Medical therapy is wrong answer Source: Bundesarchiv, Bild 146-1996-036-01 / Unknown / CC-BY-SA, commons.wikimedia.org MTB S2CK  ‐ p. 511 A 65-year-old man brought to office by daughter. He has been hopeless and helpless since his wife died 3 months ago. Daughter is worried about his isolative behavior and lack of appetite. He lost over 30 pounds. He doesn’t seem interested in getting better and believes he should have died with his wife. What is the most likely diagnosis? a. Bereavement b. Dysthymia c. Major depression d. Adjustment disorder e. Bipolar disorder MTB S2CK  ‐ p. 511  Severe symptoms just to be bereavement Depressed mood, lasts most of the day and continuously Anxiety, depression or disturbances of conduct Mood disorder with manic symptoms, at least 1 week Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Tricyclic  antidepressants – Amitriptyline – Nortriptyline Imipramine • Hypotension • Dry mouth • Constipation • Confusion MTB S2CK  ‐ p. 512 – Imipramine • Arrhythmias • Sexual side effects • Weight gain  • GI disturbances Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Monoamine  oxidase inhibitors - Phenelzine - Isocarboxazid Tranylcypromine • Monitor diet, given that  food rich in tyramine will  produce hypertension  - Safe foods include white wine and processed cheese MTB S2CK  ‐ p. 512 - Tranylcypromine and processed cheese - Unsafe foods include red wine, aged cheese, and chocolate Source: Vincent van Gogh, Still life with bottle, two glasses, cheese and bread. commons.wikimedia.org Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Serotonin selective  reuptake inhibitors  - Fluoxetine - Paroxetine Sertraline • Headaches • Weight changes • Sexual side effects  • GI disturbances MTB S2CK  ‐ p. 512 - Sertraline - Citalopram - Escitalopram - Fluvoxamine Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Serotonin norepinephrine  reuptake inhibitors  - Venlafaxine - Duloxetine Desvenlafaxine • Hypertension  • Blurry vision • Weight changes • Sexual side effects MTB S2CK  ‐ p. 512 - Desvenlafaxine • GI disturbances  11 Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Others - Bupropion - Trazodone - Mirtazapine • Bupropion: seizures  • Trazodone: priapism • Mirtazapine: weight gain  and sedation MTB S2CK  ‐ p. 512 Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Lithium • Tremors, weight gain, GI  disturbance, nephrotoxic,  teratogenic, leukocytosis,  diabetes insipidus  MTB S2CK  ‐ p. 512 • Severe toxicity gives  confusion, ataxia, lethargy,  and abnormal reflexes Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Valproic acid • Tremors, weight gain, GI  disturbances, alopecia,  teratogenic, hepatotoxic MTB S2CK  ‐ p. 512 • Must monitor levels; toxicity  causes - Hyponatremia - Coma - Death Antidepressants, Mood Stabilizers,  Electroconvulsive Therapy Type of medication  Adverse effects • Lamotrigine • Electroconvulsive  therapy  • Stevens‐Johnson syndrome • Headaches, transient memory loss  MTB S2CK  ‐ p. 512 Source: commons.wikimedia.org What is the single most effective treatment for depression? a. Electroconvulsive therapy b. Fluoxetine c. Venlafaxine d. Imipramine e. Phenelzine  Equally efficacious, but the SSRIs are used more frequently due to side-effect profiles MTB S2CK  ‐ p. 513 Serotonin Syndrome Potentially life-threatening • From use of SSRIs, often with interactions between drugs, overdose, or recreational use of drugs that are serotonergic in origin SymptomsSymptoms • Cognitive effects – Agitation, confusion, hallucinations, hypomania MTB S2CK  ‐ p. 513 12 Serotonin Syndrome • Autonomic effects – Sweating, hyperthermia, tachycardia, nausea, diarrhea, shivering • Somatic effects – Tremors, myoclonus Treatment • Stop SSRI medication • Symptomatic treatment of fever, diarrhea, hypertension • Cyproheptadine (serotonin antagonist) MTB S2CK  ‐ p. 513 Psychotic Disorders Schizophrenia  Delusional Disorder    Classification of Psychotic Disorders Brief Psychotic Disorder Duration of symptoms • > 1 day, but < 1 month Symptoms • Delusions • Hallucinations Treatment • Antipsychotic medication • Hallucinations • Disorganized speech • Grossly disorganized • Catatonic behavior MTB S2CK – p. 513 Classification of Psychotic Disorders Schizophreniform Disorders Duration of symptoms • > 1 month, but < 6 months Symptoms • Delusions • Negative symptoms – Flat affect – Poor grooming – Social withdrawal Delusions • Hallucinations • Disorganized speech • Grossly disorganized • Catatonic behavior Treatment • Antipsychotic medication MTB S2CK – p. 513 Classification of Psychotic Disorders Schizophrenia Duration of symptoms • > 6 months Symptoms • Delusions • Hallucinations • Severely affects level of functioning Treatment • Antipsychotic• Hallucinations • Disorganized speech • Grossly disorganized • Catatonic behavior • Negative symptoms Antipsychotic medication MTB S2CK – p. 513 Psychotic Disorders • Duration of symptoms distinguishes brief psychosis, schizophreniform, and schizophrenia • If no time is mentioned, always choose schizophrenia as the correct answer to the “What is the most likely diagnosis?” question y g q MTB S2CK – p. 514 13 Schizophrenia/Definition • Thought disorder: impairs judgment, behavior, and ability to interpret reality • At least 6 months and must affect functioning • Incidence: men = women – Affects men at young age • Urine drug screen – Cocaine – Amphetamine MTB S2CK – p. 514 Schizophrenia/Definition A schizophrenic patient at the Glore Psychiatric Museum made this piece of cloth and it gives us a peek into her mind. Source: Cometstarmoon, commons.wikimedia.org Types of Schizophrenia/Diagnostic criteria Paranoid • Delusions or hallucinations, mostly persecutory or grandiose type • Most common type of schizophrenia • Later age of onset CatatonicCatatonic • Psychomotor disturbances from retardation to excitation – Stupor, rigidity, excitement, or posturing • Mutism is common MTB S2CK – p. 514 Types of Schizophrenia/Diagnostic criteria Disorganized • Marked regression to disinhibited behavior with little contact with reality • Typically appear disheveled and have bizarre emotional responsesbizarre emotional responses • Worst prognosis and earliest age of onset MTB S2CK – p. 514 Types of Schizophrenia/Diagnostic criteria Residual • Lack of positive symptoms – Hallucinations – Delusion • Presence of negative symptoms Flat affect– Flat affect – Poor grooming – Social withdrawal Undifferentiated • Characterized by not meeting criteria for other types MTB S2CK – p. 514 Schizophrenia/Treatment • Hospitalize: acutely psychotic • Ensure patient safety, administer atypical antipsychotic such as – Risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, or paliperidone • In emergency situation where intramuscular medication is needed consider – Olanzapine or ziprazidone – Haloperidol may be used, but has more side effects MTB S2CK – p. 514‐515 14 Schizophrenia/Treatment • If noncompliant with medication – Long-acting antipsychotic • Risperidone: first-line – Haloperidol may be used, more side effects • Clozapine – Use when NO response to a trial of typical or atypical antipsychotics – Never used as first-line MTB S2CK – p. 515 Schizophrenia/Treatment • Know the differences in the side effect profiles of the atypical antipsychotics • It’s common to have 2 appear on the test; you need to pick the best based ontest; you need to pick the best based on side effects MTB S2CK – p. 515 Adverse Effects of  Atypical Antipsychotic Medications Less incidence of movement disorders Olanzapine Risperidone Quetiapine Greater incidence of diabetes and weight gain; avoid in diabetic & obese Greater incidence of movement disorders MTB S2CK – p. 515 Ziprasidone Clozapine Increased risk of prolongation of QT interval; avoid in conduction defects High risk of agranulocytosis; monitor CBC on regular basis; never used as first- line treatment given side- effect profile 22-year-old woman with schizophrenia. She’s 30 pounds overweight and suffers from type 2 DM. She is concerned about her medications and asks for advice. Which of the following would be most indicated in this patient? a. Aripiprazole b. Olanzapine c. Quetiapine d. Clozapine e. Risperidone MTB S2CK – p. 515  Highest risk of metabolic abnormalities Have medium risk Management of Adverse Effects of Atypical Antipsychotic Medications Hours to days Acute dystonia Muscle spasms • Torticollis • Laryngeal spasms • Occulogyric crisis • Benztropine • Trihexyphenidyl • Diphenhydramine Onset of symptoms Symptoms Treatment MTB S2CK – p. 516 WeeksAkathisia • Occulogyric crisis • Generalized restlessness • Pacing • Rocking • Inability to relax • Reduce dose • Beta blockers • Switch to atypical Acute dystonia Muscle spasms Source: James Heilman, MD, commons.wikimedia.org 15 Management of Adverse Effects of Atypical Antipsychotic Medications Tardive dyskinesia Rare before 6 months Abnormal involuntary movements of • Head • Limb • Trunk • Switch to atypical antipsychotic • Clozapine Onset of symptoms Symptoms Treatment MTB S2CK – p. 516 Neuroleptic malignant syndrome months • Trunk • Perioral, most common has least risk Not time limited • Muscular rigidity • Fever • Autonomic changes • Agitation • Obtundation Dantrolene or bromocriptine 23-year-old man recently diagnosed with schizophrenia is started on haloperidol. Within a few hours he develops muscle stiffness. His eyes roll upward and he cannot move them down. What is the most likely diagnosis? a Tardive dyskinesia 6 mo. involuntary, perioral movementsa. Tardive dyskinesia b. Neuroleptic malignant syndrome c. Akathisia d. Serotonin syndrome e. Acute dystonic reaction MTB S2CK – p. 516  6 mo. involuntary, perioral movements No time, muscular rigidity, fever Weeks. Generalized restlessness, pacing, rocking, inability to relax SSRIs Delusional Disorder  Characterized by • Non-bizarre delusions for > 1 month and NO impairment in level of functioning • The patient may believe p y the country is about to be invaded, but he or she still obeys the law, goes to work, and pays bills MTB S2CK – p. 516 Source: commons.wikimedia.org Delusional Disorder  • Hallucinations aren’t present Treatment • Atypical antipsychotic: first-line therapy • Psychotherapy to help promote reality testing MTB S2CK – p. 516 Anxiety Disorders Panic Disorder Phobias  Panic Disorder/Definition • Is the experience of intense anxiety along with feelings of dread and doom MTB S2CK – p. 517 Source: commons.wikimedia.org 16 Panic Disorder/Definition This is accompanied by at least 4 symptoms  of autonomic hyperactivity such as • Diaphoresis • Trembling • Chest pain • SOB • Nausea • Dizziness• Chest pain • Fear of dying • Chills • Palpitations • Dizziness • Dissociative symptoms • Paresthesias MTB S2CK – p. 517 Panic Disorder/Definition • Last < 30 minutes and may be accompanied by agoraphobia – Fear of places where escape is felt to be difficult • Typically in women, can occur at any time, and usually has no specific stressor • R/O thyroid disease, hypoglycemia, and cardiac disease MTB S2CK – p. 517 Panic Disorder/Treatment   • SSRIs, typically – Fluoxetine, paroxetine, and sertraline are indicated for this disorder • Along with SSRIs, patients may benefit from benzodiazepines (e.g., alprazolam) – Begin with both g – Then taper the benzodiazepine (potential abuse) • Behavioral and individual therapy – Helpful But – Not sufficient as only treatment MTB S2CK – p. 517 Which is the first-line treatment for panic disorder? a. Alprazolam b. Buspirone c Sertraline Generalized anxiety Panic attack c. Sertraline d. Imipramine e. Fluvoxamine MTB S2CK – p. 517  Major depression, enuresis Not 1st-line Phobias Definition • Fear of an object or situation and the need to avoid it Specific phobia • Fear of an object (e.g., animals, heights, or cars) • May be learned, involves 2 main types MTB S2CK – p. 517‐518 Source: Kilarin, commons.wikimedia.org Types of Phobias Social phobia • Fear of a situation – Public restrooms – Eating in public – Public speaking • Situations where something potentially embarrassing may happen MTB S2CK – p. 518 Source: Alex.Ramek, commons.wikimedia.org 17 Phobias/Diagnosis and Treatment Diagnosis • History of – Anxiety symptoms in specific situations Or – When in contact with feared objects Treatment • Behavioral modification techniques such as – Systematic desensitization: • Expose individuals to their feared objects moving from least  most anxiety-provoking MTB S2CK – p. 518 Phobias/Treatment  • Relaxation techniques such as – Breathing Or – Guided imagery Beta blockers (e g atenolol or propanolol) are MTB S2CK – p. 518 Beta blockers (e.g., atenolol or propanolol) are used for performance anxiety such as stage fright. They are given 30 minutes to 1 hour before performance. 40-year-old man referred to psychiatrist because he is “too shy.” He has problems going to parties, feels anxious about getting close to others, and stays at home in fear that others would laugh at him. When confronted by others, he develops severe anxiety as well as hyperventilation and increased sweating. Which is the most likely diagnosis?Which is the most likely diagnosis? a. Panic disorder b. Social anxiety c. Generalized anxiety disorder d. Specific phobia e. Acute stress disorder MTB S2CK – p. 518  Intense anxiety, dread and doom, 4 autonomic hyperactivity symptoms Fear of an object Stressor, 2 days to 1 month, relive the event Chronic worrying about things that don’t merit concern Obsessive Compulsive  Disorder  Obsessive Compulsive Disorder (OCD)/ Definition  • Obsessions alone Or, most commonly • Combination of obsessions and l icompulsions • Typically affect the individual’s level of functioning MTB S2CK – p. 518 Source: Lars Klintwall Malmqvist, commons.wikimedia.org Difference between Obsessions and  Compulsions Obsessions • Thoughts that are intrusive, senseless, and distressing, thus increasing anxiety • Includes fear of Compulsions • Rituals such as counting and checking done to neutralize thoughts • Time consuming and tends to lower anxietyIncludes fear of contamination tends to lower anxiety MTB S2CK – p. 519 Source: commons.wikimedia.org 18 OCD/Diagnosis and Treatment   Diagnosis • More frequent in young patients • Incidence: men = women • OCD can coexist with Tourette disorder Treatment • SSRIs: treatment of choiceSSRIs: treatment of choice – Most common, first-line: fluoxetine, paroxetine, sertraline, citalopram, or fluvoxamine • Main behavioral therapy used – Exposure and response prevention MTB S2CK – p. 519 Posttraumatic Stress Disorder  and Acute Stress Disorder  Posttraumatic Stress Disorder (PTSD) and  Acute Stress Disorder/Definition  • In both, individuals have been exposed to a stressor to which they react with fear and helplessness • Patients continually li h d • Usually overwhelming (e.g., war, rape, hurricanes, or earthquakes) relive the event and avoid anything that reminds them of event MTB S2CK – p. 519 Source: Department of Defense visual information (DVIC) Author: US Army, Office of War Information (OWI) PTSD and Acute Stress Disorder/Definition • Affect the patient’s level of functioning Other symptoms • Increased startle response • Hypervigilance • Sleep disturbances • Anger outbursts • Concentration difficulties MTB S2CK – p. 519 Difference between PTSD and  Acute Stress Disorder PTSD • Symptoms last for > 1 month Acute stress disorder • Symptoms last for > 2 days and a maximum of 1 thmonth • They occur within 1 month of traumatic event MTB S2CK – p. 519 PTSD and Acute Stress Disorder/Diagnosis  • Main feature – Determine the time period when traumatic events occurred in relationship to symptoms • Rule out – Depression and substance abuse • Both worsen diagnosis MTB S2CK – p. 519‐520 19 PTSD and Acute Stress Disorder/Treatment • First-line treatment – Paroxetine and sertraline • Relaxation techniques and hypnosis, proven helpful • Psychotherapy after traumatic events• Psychotherapy after traumatic events will allow – Development of coping techniques and acceptance of event MTB S2CK – p. 520 35-year-old woman with palpitations, dizziness, and increased sweating for 8 months. Has visited numerous physicians, none have been helpful. Her husband is concerned because she cannot relax and worries about everything. She worries about her parents’ health even though they are healthy. She worries about her finances, although her husband assures her they’re financially secure. Wh t i th t lik l di i ?What is the most likely diagnosis? a. Generalized anxiety disorder b. Phobias c. Panic disorder d. Adjustment disorder e. Social anxiety MTB S2CK – p. 520  Fear of an object or a situation Maladaptive reaction to a stressor Anxiety to social interactions, situations Intense anxiety, dread and doom, 4 autonomic hyperactivity symptoms Generalized Anxiety Disorder  Generalized Anxiety Disorder/Definition  • Excessive anxiety and worry about most things, lasting > 6 months • Typically, anxiety is out of proportion to event • Accompanied by – Fatigue – Concentration difficultiesConcentration difficulties – Sleep problems – Muscle tension – Restlessness • Usually women, who complain of feeling anxious as long as they can remember MTB S2CK – p. 520 Generalized Anxiety Disorder/Treatment  • SSRIs – Fluoxetine, paroxetine, sertraline, or citalopram • Venlafaxine and buspirone have also been usedbeen used • Psychotherapy and behavioral therapy – Beneficial – Not considered first-line MTB S2CK – p. 520 Antianxiety Medications and  Their Adverse Effects  Antianxiety medication  • Benzodiazepines – Diazepam – Lorazepam – Clonazepam – Alprazolam Adverse effects  • Sedation • Confusion • Memory deficits • Respiratory depression And – Oxazepam – Chlordiazepoxide – Temazepam – Flurazepam • Buspirone • Addiction potential • Headaches • Nausea • Dizziness MTB S2CK – p. 521 20 Antianxiety Medications and  Their Specific Indications  Lorazepam • Used frequently in emergency situations because it can be given intramuscularly Clonazepam • May be used if addiction is a concern longer• May be used if addiction is a concern, longer half-life Chlordiazepoxide, oxazepam • Used frequently in treatment of alcohol withdrawal MTB S2CK – p. 521 Antianxiety Medications and  Their Specific Indications  Alprazolam • Used frequently in panic disorder Flurazepam temazepam triazolamFlurazepam, temazepam, triazolam • Approved as hypnotics (rarely used) MTB S2CK – p. 521 Generalized Anxiety Disorder  Flumazenil is a benzodiazepine antagonist used only when • The overdose is acute And: • You’re certain that there’s no chronic dependence MTB S2CK – p. 521 Flumazenil can cause seizures in benzodiazepine- dependent patients. It causes acute withdrawal: tremor or seizures similar to delirium tremens (alcohol withdrawal). Substance‐Related Disorders Specific Substance Abuse/Definition  Intoxication • Reversible experience - substance leads to either psychological or physiological changes Withdrawal • Cessation or reduction of a substance leading to either psychological or physiological changeseither psychological or physiological changes MTB S2CK  ‐ p. 521 Source: commons.wikimedia.org Substance‐Related Disorders/Definition Abuse • Maladaptive pattern - substances that leads to – Engaging in hazardous situations – Legal problems – Inability to fulfill obligations – Continued use despite adverse consequences MTB S2CK  ‐ p. 521 21 Substance‐Related Disorders/Definition Dependence • Maladaptive pattern, substances leads to – Tolerance • Withdrawal when trying to cut down • Patients spend a great• Patients spend a great deal of time engaging in drug use • Continued use despite adverse consequences MTB S2CK  ‐ p. 521 Source: Carlos t . commons.wikimedia.org Intoxication and Withdrawal/Alcohol Source: GeographBot, commons.wikimedia.org Alcohol Intoxication Withdrawal • Talkative • Sullen • Gregarious Signs & Symptoms • Tremors • Hallucinations • Seizures MTB S2CK  ‐ p. 522 Gregarious • Moody • Disinhibited Mechanical ventilation, if severe Seizures • Delirium tremens • Benzodiazepines • Thiamine • Multivitamins • Folic acid Treatment Intoxication and Withdrawal/ Amphetamines & Cocaine Amphetamines & CocaineIntoxication Withdrawal • Euphoria • Hypervigilance • Autonomic hyperactivity • Weight loss Signs & Symptoms • Anxiety • Tremulousness • Headache • Increased Appetite Signs & Symptoms MTB S2CK  ‐ p. 522 • Weight loss • Pupillary dilatation • Perceptual disturbances Antipsychotics and/or benzodiazepines and/or antihypertensives • Increased Appetite • Depression • Risk of suicide Bupropion and/or bromocriptine Treatment Treatment Intoxication and Withdrawal/Cannabis Source: JonRichfield, commons.wikimedia.org Cannabis Intoxication Withdrawal • Impaired motor coordination • Slowed sense of Signs & Symptoms None Signs & Symptoms Treatment MTB S2CK  ‐ p. 522 time • Social withdrawal • Increased appetite • Conjunctival injection None None Treatment Intoxication and Withdrawal/Hallucinogens  Source: Ksd5 commons wikimedia org Hallucinogens Intoxication Withdrawal • Ideas of reference • Perceptual disturbances Signs & Symptoms None Signs & Symptoms Treatment MTB S2CK  ‐ p. 522 Source: Ksd5, commons.wikimedia.org• Impaired judgment • Tremors • Incoordination • Dissociative symptoms Antipsychotics and/or benzodiazepines and/or talking down None Treatment Intoxication and Withdrawal/Inhalants Hallucinogens Intoxication Withdrawal • Belligerence • Apathy • Aggression Signs & Symptoms None Signs & Symptoms Treatment MTB S2CK  ‐ p. 522 • Aggression • Impaired judgment • Stupor • Coma Antipsychotics None Treatment 22 Intoxication and Withdrawal/Opiates Source: Eleassar, commons.wikimedia.org Opiates Intoxication Withdrawal • Apathy • Dysphoria • Pupillary constriction Signs & Symptoms • Fever • Chills • Lacrimation Abdominal cramps Signs & Symptoms MTB S2CK  ‐ p. 522 • Drowsiness • Slurred speech • Coma • Death Naloxone • Abdominal cramps • Muscle spasms • Diarrhea • Clonidine • Methadone Or • Buprenorphine Treatment Treatment Intoxication and Withdrawal/ Phencyclidine (PCP)  PCPIntoxication Withdrawal • Belligerence • Psychomotor agitation • Violence Signs & Symptoms MTB S2CK  ‐ p. 522 Source: Jara172, commons.wikimedia.org • Nystagmus • HTN • Seizures • Antipsychotics and/or benzodiazepines and/ or talking down None None Treatment Signs & Symptoms Treatment Intoxication and Withdrawal/Anabolic Steroids  Source: Cristian navas roman Anabolic Steroids Intoxication Withdrawal • Irritability • Aggression Signs & Symptoms • Depression • Headaches Signs & Symptoms MTB S2CK  ‐ p. 522 Source: Cristian navas roman, commons.wikimedia.org• Mania • Psychosis Antipsychotics • Anxiety • Increased concern over body’s physical state SSRIs Treatment Treatment Substance‐Related Disorders/Treatment If you suspect someone is an alcoholic, do CAGE test. Two positive responses to four questions are considered a positive test and indicate that further assessment is warranted. C - Have you ever felt you should cut down on your drinking? A - Have people annoyed you by criticizing your drinking? G - Have you ever felt bad or guilty about your drinking? E - Eye opener: Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangover? MTB S2CK  ‐ p. 523 Substance‐Related Disorders/Treatment • Detoxification – Usually 5-10 days – Mostly in hospital settings to assure safe detoxification • Rehabilitation – Usually 28 days or more with a focus on relapse prevention techniques • Alcoholics Anonymous • Narcotics Anonymous • Pharmacologic treatments often include: – Disulfram (acetaldehyde dehydrogenase inhibitor) – Naltrexone (opioid receptor antagonist) – Acamprosate MTB S2CK  ‐ p. 523 65-year-old engineer suffered femur fracture and some cuts and bruises after being involved in an MVA. He’s admitted to the medicine floor and started on oxycodone. The day after admission, he appears confused with observable tremors in both extremities. He becomes concerned about “bugs on the walls” in his room and asks for your help.  Typically after injury Constipation, miosis >1 day but 6 months, delusions, hallucinations, disorganized speech & behavior What is the most likely explanation for his symptoms? a. Brain concussion b. Alcohol withdrawal c. Oxycodone intoxication d. Brief psychotic disorder e. Schizophrenia 23 Somatoform Disorder,  Factitious Disorder, and  MalingeringMalingering Somatoform Disorders • Characterized by – Physical symptoms with no medical explanation • Symptoms severe enough to adversely affect level of functioning • More frequent in young women • Usually has psychological component which the• Usually has psychological component, which the patient is unaware • Treatment of choice: psychotherapy – Source of symptoms is psychological MTB S2CK  ‐ p. 523 Types of Somatoform Disorders/ Diagnostic criteria  Somatization disorder • Patients must have at least – 4 Pain – 2 GI 1 Se al Hypochondriasis • Patients believe that they have some specific disease despite constant reassurance– 1 Sexual And – 1 Pseudoneurological symptom reassurance MTB S2CK  ‐ p. 524 Types of Somatoform Disorders/ Diagnostic criteria  Conversion • Affects voluntary motor or sensory functions, indicative of a medical condition • Usually caused by psychological factors • Associated with “la belle indifference” – Unconcerned about impairment MTB S2CK  ‐ p. 524 Types of Somatoform Disorders/ Diagnostic criteria  Body Dysmorphic Disorder • Patients believe that some part of the body is abnormal, defective, or misshapen Pain Disorder • Main complaint: presence of pain And must have • Psychological f t i t dfactors associated with pain MTB S2CK  ‐ p. 524 Source: elovedfreak, commons.wikimedia.org 35-year-old married mother of 3 has frequent complaints of dizziness, nausea, diarrhea, vomiting, pain during intercourse, paresthesias, leg pain, stomach pain, food intolerance, and headaches. She has tried numerous medications, but none have been beneficial. Neurological examination: normal. What is the next step in the management of this patient? a. Lorazepam b. Sertraline c. Individual psychotherapy d. Lithium e. Risperidone  Anxiety disorder Fibromyalgia & depression Bipolar disorder Psychosis MTB S2CK  ‐ p. 524 24 Factitious Disorder  • Individual fakes an illness to get attention and emotional support in patient role • Either psychological or physical illness • Psychological symptoms – Hallucinations, delusions, depression, and bizarre behavior • Physical symptoms – Abdominal pain, fever, nausea, vomiting, or hematomas MTB S2CK  ‐ p. 524 Factitious Disorder • Inflict life-threatening injuries on themselves • Behavior may be compulsive at times • Formerly known as Münchausen syndrome • Factitious disorder by proxy, caretaker fakes signs and symptoms in another person – Usually a child in order to assume the sick role by– Usually a child, in order to assume the sick role by proxy as the caregiver MTB S2CK  ‐ p. 525 Factitious Disorder • Typically, women with a history of being employed in healthcare • Men more often have physical symptoms • Patient’s ultimate goal: admission to hospital • Always exclude any medical disorder with similar symptoms MTB S2CK  ‐ p. 525 Factitious disorder cannot be diagnosed without first ruling out medical illness Factitious Disorder/Treatment  • No specific therapy has been proven to be effective • When a child is involved in factitious disorder by proxy –Contact child protective services to ensure child’s safety MTB S2CK  ‐ p. 525 Malingering Characterized by • Conscious production of signs and symptoms for an obvious gain, such as – Avoiding work – Evading criminal prosecution OrOr – Achieving financial gain • Not a mental illness MTB S2CK  ‐ p. 525 Malingering/Diagnosis Diagnosis • More frequently in prisoners and military personnel • Typically diagnosed when there’s a discrepancy betweendiscrepancy between – Patient’s complaints And – Actual physical or laboratory findings MTB S2CK  ‐ p. 525 25 Malingering If medical evaluation reveals malingering • Confront patient with the outcome A lack of cooperation from MTB S2CK  ‐ p. 525 A lack of cooperation from patients is characteristic of malingering Adjustment Disorder Adjustment Disorder  Characterized by • Maladaptive reaction to an identifiable stressor – Loss of job – Divorce Or • Symptoms – Anxiety – Depression – Disturbances of conduct • Severe enough to cause impairment in functioning – Failure in school • Usually occur within 3 months of stressor and must remit within 6 months of removal of stressor MTB S2CK  ‐ p. 525 Adjustment Disorder/Treatment  Treatment of choice • Psychotherapy • Both individual and group therapy have been used effectively MTB S2CK  ‐ p. 525 Personality Disorders Personality Disorders  Characterized by • Personality patterns that are: – Pervasive – Inflexible – Maladaptive Cl t A Cl t B Cl t C MTB S2CK  ‐ p. 525‐526 • Paranoid • Schizoid • Schizotypal • Histrionic • Antisocial • Borderline • Narcissistic Cluster A Cluster B • Avoidant • Dependent • Obsessive compulsive Cluster C 26 Types of Personality Disorders Paranoid Schizoid • Suspicious • Mistrustful • Secretive • Isolated A d • Choice of solitary activities • Lack of close friends E i l Schizotypal • Ideas of reference • Magical thinking Odd thi ki MTB S2CK  ‐ p. 526 And • Questioning loyalty of family & friends • Emotional coldness • No desire for or enjoyment of close relationships • Odd thinking • Eccentric behavior • Increased social anxiety • Brief psychotic episodes Types of Personality Disorders • Must be center of attention • Inappropriate sexual behavior Histrionic MTB S2CK  ‐ p. 526 • Self-dramatization • Use physical appearance to draw attention to self Types of Personality Disorders • Failure to conform to social rules • Deceitful • Lack of remorse I l i Antisocial • Unstable relationships • Impulsive • Recurrent suicidal behaviors Ch i f li Borderline • Grandiose sense of self • Belief that they are special • Lack empathy S f Narcissistic MTB S2CK  ‐ p. 526 • Impulsive • Aggressive towards others • Irresponsible • Must be 18+ • Chronic feelings of emptiness • Inappropriate anger • Dissociative symptoms when severely stressed  Brief psychotic episodes • Sense of entitlement • Require excessive admiration Types of Personality Disorders • Unwilling to get involved with people Avoidant • Difficulty making day-to-day decisions • Unable to Dependent • Preoccupied with details • Rigid • Orderly Obsessive compulsive MTB S2CK  ‐ p. 526 with people • Views self as socially inept • Reluctant to take risks • Feelings of inadequacy assume responsibility • Unable to express disagreement • Fear of being alone • Seeks relationship as source of care y • Perfectionists • Excessively devoted to work • Inflexible Personality Disorders/Treatment • Individual psychotherapy • Medications if mood or anxiety symptoms are present MTB S2CK  ‐ p. 526 Which of the following personality disorders has been associated with positive psychotic symptoms? a. Borderline b Histrionic  & Schizotypal b. Histrionic c. Schizoid d. Paranoid e. Antisocial MTB S2CK  ‐ p. 527 Not associated 27 Eating Disorders Anorexia Nervosa Bulimia Nervosa Eating Disorder Not  Otherwise Specified 15-year-old girl brought to clinic by her mother, who found her vomiting in the bathroom. She vomits daily after each meal and exercises excessively. She has numerous calluses on her hands as well as cavities. She is 5’5’’ and weighs 90 pounds. What is her most likely diagnosis? a. Bulimia nervosa b. Anorexia nervosa c. Eating disorder not otherwise specified d. Obesity e. Atypical depression MTB S2CK  ‐ p. 527  Frequent binge eating, normal weight, obesity history Neither anorexia nor bulimiaIncreased weight Increased apetite & weight Anorexia Nervosa • Characterized by – Failure to maintain a normal body weight – Fear and preoccupation of gaining weight – Body imageBody image disturbance • Unrealistic self-evaluation as overweight • Amenorrhea is common from low body weight • Deny their emaciated condition • Great concern with appearance and frequently examine and weigh themselves MTB S2CK  ‐ p. 527 Source: http://www.womenshealth.gov/body- image/eating-disorders/ Anorexia Nervosa/Diagnosis • Lose weight by – Strict caloric control – Excessive exercise – Purging • Laxative & diuretic And F ti • Bradycardia • Lanugo hair And • Edema • EKG changes – Potassium deficiency – Fasting • More frequently, teenage girls 14 -18 years of age • Severe weight loss • Hypotension y • Arrhythmia MCC of death MTB S2CK  ‐ p. 527 Anorexia Nervosa/Treatment • Hospitalization to prevent – Dehydration – Starvation – Electrolyte imbalances – Death • Psychotherapy • Behavioral therapy • SSRIs – To promote weight gain MTB S2CK  ‐ p. 528 Bulimia Nervosa Characterized by • Frequent binge eating in a discrete amount of time • Lack of control of overeating episodes • Accompanied by compensatory behavior to prevent weight gain – Purging • Laxatives & diureticsdiuretics – Fasting And – Excessive exercise • Self-evaluation influenced by body shape and weight MTB S2CK  ‐ p. 528 Source: girlshealth.gov 28 Bulimia Nervosa Diagnosis • More frequently women and later in adolescence than anorexia nervosa • Most normal weight, but history of obesity TreatmentTreatment • Doesn’t require hospitalization, unless – Severe electrolyte abnormality • Psychotherapy • SSRIs MTB S2CK  ‐ p. 528 Eating Disorder Not Otherwise Specified  • Doesn’t meet criteria for either anorexia nervosa or bulimia nervosa • Examples – Criteria for anorexia present in girls, but menstruation is normalmenstruation is normal – Anorexic patient with normal weight – Use of compensatory behavior after eating normal amounts of food MTB S2CK  ‐ p. 528 Sleep Disorders Narcolepsy Insomnia Narcolepsy • Characterized by – Excessive daytime sleepiness And – Abnormalities of REM sleep • Most frequently begins in young adulthood • Sleep studies are usually indicated in diagnosis MTB S2CK  ‐ p. 528 Source:http://www.cdc.gov/sleep/ Narcolepsy • No curative therapy • Forced daytime naps • Modafinil – To maintain alertness MTB S2CK  ‐ p. 528‐529 Psychiatric & Physical Symptoms  of Narcolepsy (Sleep Disorder) Sleep attacks • Episodic irresistible Specific feature of narcolepsy Cataplexy • Sudden Hypnogogic and hypnopompic hallucinations Sleep paralysis • Awake but unable MTB S2CK  ‐ p. 529 sleepiness And • Feeling refreshed upon awakening muscle tone loss: pathognomonic And • May be precipitated by loud noise or emotions hallucinations Hallucinations occur as patient is going to sleep and waking up to move • Typically upon awakening 29 Insomnia • Characterized by – Inability to initiate or maintain sleep • May be due to anxiety and depression • Severe enough to affect g level of functioning • Typically women who complain of feeling tired or have increased appetite and yawning MTB S2CK  ‐ p. 529 Source: nih.gov Insomnia • Sleep hygiene techniques – Going to bed and waking up at the same time – Avoiding caffeinated beverages And – Avoiding daytime naps • Behavioral modification techniques includeBehavioral modification techniques include – Using the bed only for sleeping (not for reading, watching TV, or eating) • Medical therapy – Zolpidem, eszopiclone, or zaleplon MTB S2CK  ‐ p. 529 Human Sexuality Terminology of Human Sexuality Sexual identity • Based on a person’s secondary sexual characteristics Gender role • Based on external patterns of behavior that reflect inner sense of gender identity Sexual orientationGender identity • Based on a person’s sense of maleness or femaleness, established by age 3 Sexual orientation • Based on person’s choice of love object; may be heterosexual, homosexual, bisexual, or asexual MTB S2CK  ‐ p. 529 Human Sexuality Masturbation • Normal precursor of object-related sexual behavior • All men and women masturbate • Problematic if it interferes with daily functioning H litHomosexuality • Not considered a mental illness unless it is ego- dystonic (person not happy with sexual orientation) • May be considered normal experimentation in teenagers MTB S2CK  ‐ p. 530 Types of Sexual Dysfunction Persistent or recurrent inability to attain or maintain an erection until completion of sexual act Impotence Ejaculation before penetration or just after penetration, usually due to anxiety Premature ejaculation Treatment Treatment MTB S2CK  ‐ p. 530 se ua act R/O medical causes or medication Psychotherapy, couples sexual therapy Psychotherapy, behavioral modification techniques (stop and go, squeeze), SSRI medication 30 Types of Sexual Dysfunction Prolonged and painful contraction or spasm of the vagina Usually severe enough to prevent intercourse Dyspareunia Pain associated with sexual intercourse, not diagnosed if due to medical condition Vaginismus Treatment MTB S2CK  ‐ p. 530 Treatment to prevent intercourse Psychotherapy • Psychotherapy • Dilator therapy Paraphilias • Group of disorders that are recurrent, sexually arousing, and seen more frequently in men • Usually focus on humiliation, nonconsenting partners, or use of nonliving objects • Must occur – > 6 months and cause distress – Affect level of functioning • Don’t diagnose if experimentation MTB S2CK  ‐ p. 530 Types of Paraphilias Exhibitionism • Recurrent urge to expose oneself to strangers Pedophilia • Recurrent urges or arousal toward prepubescent children Fetishism • Recurrent use of nonliving objects to achieve sexual pleasure Masochism • Recurrent urge or behavior involving the act of humiliation MTB S2CK  ‐ p. 531 Types of Paraphilias Sadism • Recurrent urge or behavior involving acts in which physical or psychological suffering of victim is exciting Transvestic fetishism • Recurrent urge or behavior involving cross dressing for sexual gratification; usually in heterosexual males MTB S2CK  ‐ p. 531 Types of Paraphilias Frotteurism • Rubbing one’s pelvis or erect penis against a nonconsenting person for sexual gratification MTB S2CK  ‐ p. 531 Source: Dschwen, commons.wikimedia.org Paraphilias/Treatment • Individual psychotherapy • Behavioral modification techniques – Aversive conditioning • Antiandrogens or SSRIs to reduce sexual drive MTB S2CK  ‐ p. 531 31 Gender Identity Disorder • Characterized by – Persistent discomfort and sense of inappropriateness regarding the patient’s assigned sex Diagnosis • Wearing opposite gender’s clothesg pp g • Using toys assigned to opposite sex • Play with opposite-sex children when young And • Feeling unhappy about one’s own sexual assignment MTB S2CK  ‐ p. 531 Gender Identity Disorder  • Patients will take hormones when older to deepen voice, if female, or soften voice, if male • Women may bind their breasts and men may hide their penis and testicles • It’s seen more frequently in young men Treatment • Sexual reassignment surgery if approved • Individual psychotherapy MTB S2CK  ‐ p. 531 Suicide Suicide • Recent suicide attempt • Complaints of suicidal thoughts • Admission of suicidal thoughts • Demonstration ofDemonstration of suicidal behaviors – Buying weapons – Giving away possessions – Writing a will MTB S2CK  ‐ p. 532 Source: samhsa.gov Source: samhsa.gov Suicide Risk Factors • Men • Older adults • Social isolation • Presence of psychiatric illness/drug abuse Treatment • Hospitalize patient • Take all threats seriously illness/drug abuse • Perceived hopelessness • Previous attempts MTB S2CK  ‐ p. 532 1 Asthma Stephen Bagley, MD Resident Physician Internal Medicine Hospital of the University of Pennsylvania Asthma/Definition Asthma or reactive airway disease • Abnormal bronchoconstriction of airways Characterized by • Reversible airway obstruction secondary to bronchial smooth muscle hyperactivitybronchial smooth muscle hyperactivity • Airway inflammation, mucus plugging, and smooth muscle hypertrophy – Can lead to chronic, irreversible airway obstruction MTB S2CK  ‐ p. 129 Asthma/Etiology • Extremely common • Etiology unknown • Associated with atopic disorders and obesity MTB S2CK  ‐ p. 129 Asthma prevalence, incidence, and hospitalization rates are increasing Asthma/Etiology Causes acute exacerbations of symptoms • Allergens such as pollen, dust mites, cockroaches, and cat dander • Infection • Changes in weather (especially cold air) • Exercise• Exercise • Catamenial (related to menstrual cycle) • Aspirin, NSAIDs, beta blockers, tobacco smoke • Gastroesophageal reflux disease (GERD) MTB S2CK  ‐ p. 129 Asthma/Presentation • Most often presents with – Wheezing – Acute onset of SOB – Cough And – Chest tightness • Increased sputum production common • Fever is often not present MTB S2CK  ‐ p. 129 Remember – all that wheezes is not asthma! Asthma/Presentation “Which of the following is most likely to be found  in an asthmatic patient?” • Symptoms worse at night • Nasal polyps • Eczema or atopic dermatitis on physical • Increased use of accessory respiratory muscles (e.g., intercostals)p y examination • Increased length of expiratory phase of respiration – I/E ratio decreases (normal is 1:2) • Hyperresonance to percussion, pulsus paradoxus MTB S2CK  ‐ p. 129‐130 2 Asthma/Presentation The answer to the “best initial test” question in asthma is based on the severity of presentation MTB S2CK  ‐ p. 130 Asthma/Diagnostic Tests The best initial test in an acute exacerbation • Arterial blood gas (ABG) or peak expiratory flow (PEF) ABG if mild earl e acerbation mild– ABG if mild, early exacerbation: mild hypoxia, respiratory alkalosis – ABG if severe, late exacerbation: severe hypoxia, respiratory acidosis MTB S2CK  ‐ p. 130 Asthma/Diagnostic Tests • Chest X-ray – Most often normal in asthma, but may show hyperinflation – Useful for excluding other disease processes • Pneumonia, CHF, pneumothorax MTB S2CK  ‐ p. 130 Asthma/Diagnostic Tests • Most accurate diagnostic test is pulmonary function testing (PFTs) • You must understand lung volumes! MTB S2CK  ‐ p. 130 Asthma/Diagnostic Tests Asthma/Diagnostic Tests PFTs in asthma show • OBSTRUCTION:  FEV1 and  FVC with a  FEV1/FVC ratio • HYPERINFLATION:  total lung capacity (TLC) • AIR TRAPPING:  in residual volume • REVERSIBILITY: in FEV1 > 12% with use of• REVERSIBILITY:  in FEV1 > 12% with use of albuterol • BRONCHIAL HYPERRESONIVENESS:  FEV1 > 20% with use of methacholine MTB S2CK  ‐ p. 131 3 15-year-old boy with occasional SOB every few weeks. Currently feels well. No medications and denies any other medical problems. Pulse is 70 and RR is 12. Chest examination is normal. Which is the single most accurate diagnostic test at this time? a. Peak expiratory flow b. Increase in FEV1 with albuterol Acute exacerbation Less likely in asymptomatic c. Diffusion capacity of carbon monoxide d. > 20% decrease in FEV1 with use of methacholine e. Increased alveolar-arterial oxygen difference (A-a gradient) f. Increase in FVC with albuterol g. Flow-volume loop on spirometry h. Chest CT scan i. Increased pCO2 on ABG MTB S2CK  ‐ p. 130  Asymptomatic Less likely in asymptomatic Best for fixed obstructions Shows nothing or hyperinflation Acute exacerbation Asymptomatic Asthma/Diagnostic Tests • Acetylcholine and histamine provoke bronchoconstriction and increase in bronchial secretions • Methacholine is artificial form of• Methacholine is artificial form of acetylcholine used in diagnostic testing MTB S2CK  ‐ p. 131 Asthma/Diagnostic Tests Additional testing options include • CBC may show an increased eosinophil count • Skin testing to identify specific allergens that provoke bronchoconstriction • Increased IgE levels suggest allergic etiology – Also seen in allergic bronchopulmonary aspergillosis MTB S2CK  ‐ p. 131 Asthma/Treatment Chronic management • Stepwise fashion of progressively adding more types of treatment if no response MTB S2CK  ‐ p. 131 Asthma/Chronic Management Mild intermittent: < 2 days/week < 2 nights/ month Inhaled short- ti b t Step 1 Mild persistent: > 2 days/week > 2 nights/month Add a long-term control agent: Step 2 Moderate persistent: daily, or > 1 night/week • Add a long- acting beta Step 3 Severe persistent: continual, frequent Increase d f Step 4 MTB S2CK  ‐ p. 131‐132 acting beta agonist SABA • Albuterol • Levalbuterol control agent: Low-dose inhaled corticosteroids (ICS) for daily use • Beclomethasone • Budesonide • Flunisolide • Fluticasone • Mometasone • Triamcinolone g agonist (LABA) to a SABA & ICS Or • Increase dose of ICS • LABA –Salmeterol Or –Formoterol dose of ICS to maximum in addition to LABA & SABA Asthma/Treatment • Alternate long-term control agents include C l d d il i hibit t ll di t Adverse effects of inhaled steroids are dysphonia and oral candidiasis – Cromolyn and nedocromil: inhibit mast cell mediator release – useful for exercise – Theophylline: phosphodiesterase inhibitor – increasing cAMP levels (cardio- and neurotoxicity) – Leukotriene modifiers: montelukast, zafirlukast, or zileuton – best with atopic patients MTB S2CK  ‐ p. 131 4 Asthma/Treatment Zafirlukast is hepatotoxic and has been associated with Churg-Strauss syndrome MTB S2CK  ‐ p. 131 Asthma/Diagnostic Tests Management of Acute Exacerbation • Step#1: determine severity of asthma exacerbation, quantified by –Decreased peak expiratory flow (PEF) –ABG with evidence of increased A-aABG with evidence of increased A a gradient or CO2 retention MTB S2CK  ‐ p. 133 Asthma/Diagnostic Tests • PEF is an approximation of FVC – No precise “normal” value – Based predominantly on height and age, not weight • PEF is used in acute assessment by seeing y g how much difference there’s from patient’s usual PEF when stable MTB S2CK  ‐ p. 133 Asthma/Treatment Management of Acute Exacerbation • Oxygen • Albuterol (often nebulized to ensure adequate delivery to lungs) +/- inhaled anticholinergic (e.g., ipratropium) • Corticosteroids: need 4-6 hours to begin to work soCorticosteroids: need 4 6 hours to begin to work, so give right away • Epinephrine injections are no more effective than albuterol and have more adverse systemic effects MTB S2CK  ‐ p. 133 Asthma/Treatment Anticholinergics • Role of ipratropium and tiotropium in asthma management unclear • In general, ipratropium should be used, but doesn’t work as rapidly as albuterolwork as rapidly as albuterol Epinephrine • Rarely used and only as a drug of last resort MTB S2CK  ‐ p. 132‐133 Asthma/Treatment Magnesium • Some modest effect in bronchodilation • Not as effective as albuterol, ipratropium, or steroids, but it does help Magnesium helps bronchospasm. MTB S2CK  ‐ p. 133 g p p Magnesium is used only in acute, severe asthma exacerbation not responsive to several rounds of albuterol while waiting for steroids to take effect. 5 Asthma/Treatment Adverse Effects of Chronic Systemic Corticosteroids • Should be a last resort because of very harsh adverse effects such as – Osteoporosis – CataractsCataracts – Adrenal suppression and fat redistribution – Hyperlipidemia, hyperglycemia, acne, and hirsutism (particularly in women) – Thinning of skin, striae, and easy bruising MTB S2CK  ‐ p. 132 Asthma/Treatment High-dose inhaled steroids rarely lead to adverse effects associated with prednisone MTB S2CK  ‐ p. 132 47-year-old man with history of asthma comes to ED with several days of increasing SOB, cough, and sputum production. RR is 34. He has diffuse expiratory wheezing and prolonged expiratory phase. Which would you use as the best indication of the severity of his asthma?a. Respiratory rate b. Use of accessory muscles c. Pulse oximetry d. Pulmonary function testing e. Pulse rate MTB S2CK  ‐ p. 132.4  Hypoxia, until imminent respiratory failure Adds nothing Subjective Short of breath Asthma/Treatment The following are not effective in acute exacerbations • Theophylline • Cromolyn and nedocromil (best ith t i i ll i lik h MTB S2CK  ‐ p. 133 with extrinsic allergies like hay fever) • Leukotriene modifiers • Omalizumab • Salmeterol Asthma/Treatment • If no response to oxygen, albuterol, and steroids or develops respiratory acidosis (increased pCO2) – Consider endotracheal intubation and mechanical ventilation MTB S2CK  ‐ p. 133 Chronic Obstructive  Pulmonary Disease 6 COPD/Definition Characterized by airflow obstruction secondary to emphysema and/or chronic bronchitis • Emphysema –Terminal airway destruction resulting in decreased elastic recoil of lungs • Normally, elastin fibers allow passive exhalation MTB S2CK  ‐ p. 134 COPD/Definition • Chronic bronchitis –Productive cough for > 3 months/year for 2 consecutive years • Both Part of COPD spectrum–Part of COPD spectrum –Results in decrease in FEV1 and FVC with increase in TLC MTB S2CK  ‐ p. 134 COPD/Etiology Tobacco smoking • Leads to almost all COPD • Destroys elastin fibers Y d k MTB S2CK  ‐ p. 134 Young and a nonsmoker, answer alpha-1 antitrypsin deficiency as most likely cause COPD/Presentation • SOB worsened by exertion • Intermittent exacerbations with  cough, sputum, and SOB often brought on by infection • “Barrel chest” from  air trapping • Muscle wasting and cachexia – COPD now thought to have a component of systemic inflammation MTB S2CK  ‐ p. 134 COPD/Diagnostic Tests “Best initial test”: chest X-ray • Increased anterior- posterior (AP) di tdiameter • Air trapping and flattened diaphragms MTB S2CK  ‐ p. 134 Source: James Heilman, MD, commons.wikimedia.org COPD/Diagnostic Tests “Most accurate diagnostic test”: PFT • Decreased FEV1, FVC, and FEV1/FVC ratio (< 70%) • Increased TLC due to  RV • Decreased DLCO in emphysema p y (destruction of alveolar septae where capillaries are found) • Incomplete improvement with albuterol • Little or no worsening with methacholine MTB S2CK  ‐ p. 134 7 COPD/Diagnostic Tests Reversibility with Inhaled Bronchodilators • COPD generally associated with IRREVERSIBLE airway obstruction But • COPD has a broad response to inhaled bronchodilators (e g albuterol)bronchodilators (e.g., albuterol) • Ranges from no reversibility to complete reversibility MTB S2CK  ‐ p. 134 Reversibility in response to bronchodilators is: > 12% increase and 200 mL increase in FEV1 COPD/Diagnostic Tests Arterial blood gas (ABG) • Acute exacerbations of COPD are associated with  pCO2 and hypoxia – Respiratory acidosis may be present if there’s insufficient metabolic compensationthere s insufficient metabolic compensation and bicarbonate level will be elevated to compensate – In between exacerbations, not all those with COPD will retain CO2 MTB S2CK  ‐ p. 134 COPD/Diagnostic Tests EKG • Right atrial hypertrophy and right ventricular hypertrophy • A-fib or multifocal atrial tachycardia (MAT) Echocardiography • Right atrial and right ventricular hypertrophy • Pulmonary hypertension MTB S2CK  ‐ p. 135 COPD/Treatment Improves Mortality and Delays Progression of Disease: only 2 interventions! • Smoking cessation • Oxygen therapy for hypoxia – PaO2 8 COPD/Treatment Possibly Improves Symptoms • Theophylline • Lung volume reduction surgery No Benefit C l• Cromolyn • Leukotriene modifiers (e.g., montelukast) MTB S2CK  ‐ p. 135 When all medical therapy is insufficient, the answer is “refer for transplantation” COPD Acute Exacerbations/Treatment • Combination of bronchodilators and corticosteroid therapy COPD exacerbation treatment MTB S2CK  ‐ p. 136 COPD exacerbation treatment is identical to asthma exacerbation treatment, but with less proven benefit COPD Acute Exacerbations/Treatment Antibiotics • For exacerbation of moderate to severe COPD – Defined as requiring hospitalization or having at least two of the three cardinal symptoms of a COPD flareCOPD flare • Dyspnea  • Sputum production  • Sputum purulence MTB S2CK  ‐ p. 136 Chronic Bronchitis Acute Exacerbations/ Treatment Antibiotics • Although viruses cause 20-50% of episodes, coverage should be provided against Streptococcus pneumoniae, H. influenzae, and Moraxella catarrhalis – Macrolides: azithromycin, clarithromycinMacrolides: azithromycin, clarithromycin – Cephalosporins: cefuroxime, cefixime – Amoxicillin/clavulanic acid – Quinolones: levofloxacin, moxifloxacin Second-line Agents • Doxycycline, TMP/SMX MTB S2CK  ‐ p. 136 COPD Acute Exacerbations/Treatment Criteria for Oxygen Use in COPD • Although the “hypoxic drive elimination” concept is incorrect • Avoid reflexively placing a patient with COPD on very high-flow 100% nonrebreather mask • Use only as much oxygen necessary to raise pO2Use only as much oxygen necessary to raise pO2 above 90% saturation MTB S2CK  ‐ p. 136 The idea of “eliminating hypoxic drive” is not accurate. Dyspneic, hypoxic patients with COPD must get oxygen Bronchiectasis &  Associated Conditions 9 Bronchiectasis/Definition • Uncommon disease from chronic destruction, remodeling, and dilation of the large bronchi • Permanent anatomic abnormality that cannot be reversed or cured MTB S2CK  ‐ p. 136 Source: Yale Rosen, commons.wikimedia.org Bronchiectasis/Etiology Single MCC • Cystic fibrosis: 50% of cases Other causes are • Infections – TB (and non-tuberculous mycobacterium) ( y ) – Pneumonia (staph or repeated aspiration) • Panhypogammaglobulinemia and immune deficiency MTB S2CK  ‐ p. 137 Bronchiectasis/Etiology • Foreign body or tumors • Allergic bronchopulmonary aspergillosis (ABPA) • Collagen vascular such as RA • Immotile cilia syndrome (Kartagenery ( g syndrome) These conditions result in repeated and persistent lung infections MTB S2CK  ‐ p. 137 Bronchiectasis/Diagnostic Tests  “Best initial test” • Chest X-ray shows – Dilated, thickened bronchi, sometimes with “tram-tracks,” which is thickening of bronchi “Most accurate test” • High-resolution CT, general rule of thumb – Sizable airways are larger in diameter than corresponding adjacent bronchial arteries MTB S2CK  ‐ p. 137 Bronchiectasis/Diagnostic Tests  MTB S2CK  ‐ p. 137 Source: Thomas P. Eberle Bronchiectasis/Diagnostic Tests  • Sputum culture Impossible to diagnose bronchiectasis without imaging study such as CT Sputum culture – Only way to determine specific bacterial etiology MTB S2CK  ‐ p. 137 10 Bronchiectasis/Treatment  1. Chest physiotherapy (“cupping and clapping”) and postural drainage – Essential for dislodging plugged-up bronchi 2. Treat each episode of infection as it arises – Same antibiotics as for COPD exacerbations – Only difference is inhaled antibiotics seem to have some efficacy 3. Surgical resection – Focal lesions MTB S2CK  ‐ p. 138 Allergic Bronchopulmonary Aspergillosis  (ABPA) • Hypersensitivity to fungal antigens that colonize bronchial tree • Almost exclusively with asthma and atopic disorders • Look for• Look for – Asthmatic with recurrent episodes of brown-flecked sputum and transient infiltrates on X-ray • Cough, wheezing, hemoptysis, bronchiectasis MTB S2CK  ‐ p. 138 Allergic Bronchopulmonary Aspergillosis  (ABPA)/Diagnostic Tests • Peripheral eosinophilia • Skin test reactivity to aspergillus antigens • Precipitating antibodies to aspergillusp g p g on blood test • Elevated serum IgE levels • Pulmonary infiltrates on chest X-ray or CT MTB S2CK  ‐ p. 138 Allergic Bronchopulmonary Aspergillosis  (ABPA)/Treatment 1. Oral steroids (prednisone) for severe cases – Inhaled steroids aren’t effective for ABPA 2. Itraconazole or voriconazole orally for i drecurrent episodes MTB S2CK  ‐ p. 138 Inhaler can’t deliver high enough dose steroids to be effective in ABPA Cystic Fibrosis (CF)/Etiology • Autosomal recessive from mutation that codes for chloride transport – Known as CF transmembrane conductance regulator (CFTR) • Mutations in CFTR gene damage chloride g g and water transport across apical surface of epithelial cells in exocrine glands throughout the body MTB S2CK  ‐ p. 138‐139 Source: Mucoviscidose.PNG: Mirmillon, commons.wikimedia.org Lungs • Bronchiectasis • Bronchitis • Broncholitis • Pneumonia • Atelectasis • Hemoptysis • Pneumothorax • Reactive airway • Cor pulmonale • Respiratory failure • Mucoid impaction of the bronchi • Allergic bronchopulmonary aspergillosis • Leads to abnormally thick mucus in Cystic Fibrosis/Etiology Nose & Sinuses • Nasal polyps • Sinusitis Liver General • Growth failure (malabsorption) • Vitamin deficiency states •Vitamins A,D,E,K Source: Maen K Abu Househ, commons .wikimedia.org Reactive airway disease MTB S2CK  ‐ p. 139 Liver • Hepatic steatosis • Portal hypertension Gallbladder • Biliary cirrhosis • Neonatal obstructive jaundice • Cholelithiasis Heart • Right ventricular hypertrophy • Pulmonary artery dilation 11 Cystic Fibrosis/Etiology Intestines • Meconium ileus Spleen • Hypersplenism Stomach • GERD Pancreas • Pancreatitis I li d fi i Bone • Hypertrophic osteoarthropathy • Clubbing • Arthritis • Osteoporosis Source: Maen K Abu Househ, commons .wikimedia.orgMTB S2CK  ‐ p. 139 • Meconium ileus • Meconium peritonitis • Rectal prolapse • Intussusception • Volvulus • Fibrosing colonopathy (strictures) • Appendicitis • Intestinal atresia • Distal intestinal obstruction syndrome • Inguinal hernia • Insulin deficiency • Symptomatic hyperglycemia • Diabetes Reproductive • Infertility • Aspermia, absence of vas deferens • Amenorrhea • Delayed puberty Cystic Fibrosis/Etiology • Damaged mucus clearance decreases ability to get rid of inhaled bacteria Neutrophils in CF dump tons of DNA into airway secretions MTB S2CK  ‐ p. 139 clogging them up Cystic Fibrosis/Etiology Source: nih.gov Cystic Fibrosis/Presentation • Over 1/3 CF patients are adults Look for – Young adult with chronic lung disease • Cough • Sputum • Hemoptysisp y • Bronchiectasis • Wheezing • Dyspnea And – Recurrent episodes of infection • Sinus pain and polyps are common MTB S2CK  ‐ p. 139 • Meconium ileus: infants with abdominal distention • Pancreatic insufficiency (in 90%) Cystic Fibrosis/Presentation Gastrointestinal Involvement • Recurrent pancreatitis • Distal intestinal obstruction • Biliary cirrhosis with steatorrhea and vitamin A, D, E, and K malabsorption y MTB S2CK  ‐ p. 139 Islets spared, beta cell function is normal until much later in life Cystic Fibrosis/Presentation Genitourinary Involvement • Men are often infertile – 95% have azoospermia, vas deferens missing in 20% • Women are infertile because• Women are infertile because – Chronic lung disease alters menstrual cycle And – Thick cervical mucus blocks sperm entry MTB S2CK  ‐ p. 139 12 Cystic Fibrosis/Diagnostic Tests “Most accurate test”: increased sweat chloride test • Pilocarpine increases acetylcholine levels  increases sweat production – Chloride levels in sweat > 60 mEq/L in CF on repeated testing establishes diagnosis • Genotyping, not as accurate as increased sweat chloride level – Because there are so many different types of mutations leading to CF MTB S2CK  ‐ p. 139 Cystic Fibrosis/Diagnostic Tests • Sputum Culture – Nontypable Haemophilus influenzae – Pseudomonas aeruginosa – Staphylococcus aureus – Burkholderia cepacia– Burkholderia cepacia MTB S2CK  ‐ p. 140 Cystic Fibrosis/Treatment 1. Antibiotics are routine – Eliminating colonization: difficult – Sputum culture: essential to guide therapy – Inhaled aminoglycosides: almost exclusively limited to CF 2. Inhaled recombinant human deoxyribonuclease ( hDN )(rhDNase) – Breaks down massive amounts of DNA in respiratory mucus that clogs up airways 3. Inhaled bronchodilators – Albuterol 4. Lung transplantation MTB S2CK  ‐ p. 140 Cystic Fibrosis/Treatment Gross hemoptysis Unsuccessful Rigid bronchoscopy • Place patient “bad lung-side down” – Helps prevent bleeding into “healthier” lung, which is providing most of oxygen exchange Embolization • Interventional radiology Pneumonia – Part 1  Community‐Acquired Pneumonia/Definition • Community-acquired pneumonia (CAP) – Pneumonia occurring before hospitalization Or – Within 48 hours of hospital admission MTB S2CK  ‐ p. 140 13 CAP/Definition • Most common infectious cause of death in U.S. • MCC: Streptococcus pneumoniae MTB S2CK  ‐ p. 140 CAP/Etiology Haemophilus influenzae COPD Klebsiella pneumoniae • Alcoholism • Diabetes Mycoplasma pneumoniae • Young • Healthy patients Common Pathogens in CAP & Their Associations Legionella Coxiella burnetii • Animals at time of giving birth • Veterina- • Contamin- ated water sources • Air conditioning MTB S2CK  ‐ p. 141 Staphylococcus aureus Recent viral infection (influenza) Anaerobes • Poor dentition • Aspiration Chlamydophila pneumoniae Hoarseness Chlamydia psittaci Birds rians • Farmers conditioning • Ventilation systems CAP/Presentation All forms of pneumonia present with • Fever and cough Severe infection • Associated with dyspnea • Distinguished by abnormalities of – Vital signs (tachycardia, hypotension, tachypnea) Or – Mental status MTB S2CK  ‐ p. 141 Dyspnea, high fever, and abnormal chest X-ray are main ways to distinguish pneumonia from bronchitis CAP/Presentation • Abdominal pain or diarrhea can occur with infection in lower lobes irritating intestines through diaphragm – Legionella is particularly known for causing diarrhea • Chills or “rigors” are sometimes a sign of bacteremiabacteremia – S. pneumo would be most common • Chest pain (often pleuritic) occurs from inflammation of pleura • Hypothermia is as bad as fever in terms of pathologic significance MTB S2CK  ‐ p. 141 CAP/Presentation USMLE S2 may play abnormal breath sounds as part of multimedia and ask you to recognize them • Dullness to percussion if there’s effusion • “Bronchial” breath sounds and egophony consolidation of air spaces MTB S2CK  ‐ p. 141 CAP/Presentation Klebsiella pneumoniae Hemoptysis from necrotizing disease Mycoplasma pneumoniae Dry cough, rarely severe bullous Pneumocystis AIDS with 14 CAP/Presentation “Dry” or non-productive cough • Mycoplasma • Viruses • Coxiella • Pneumocystis • Chlamydia MTB S2CK  ‐ p. 142 CAP/Presentation • Preferentially involve interstitial space • Air spaces of alveoli empty –That’s why there’s less sputum production! MTB S2CK  ‐ p. 142 Specific sputum colors are useless in determining etiology CAP/Diagnostic Tests • “Best initial test” for all respiratory infections – Chest X-ray: but can’t determine specific etiology • Sputum Gram stain and sputumSputum Gram stain and sputum culture – Best ways to first determine specific etiology – Many organisms won’t be detected MTB S2CK  ‐ p. 142 CAP/Diagnostic Tests Atypical pneumonia • Organism not visible on Gram stain and not culturable on standard blood agar – Mycoplasma Chlamydophila– Chlamydophila – Legionella – Coxiella And – Viruses MTB S2CK  ‐ p. 142 30-50% of cases of CAP CAP/Diagnostic Tests MTB S2CK  ‐ p. 142 Right middle lobe infiltrate characteristic of bacterial pneumonia. Source: Nirav Thakar, MD CAP/Diagnostic Tests Chest X-ray • Bilateral interstitial infiltrates with – Mycoplasma Viruses • Nonproductive cough • X-rays lag behind clinical findings– Viruses – Coxiella – Pneumocystis – Chlamydia clinical findings MTB S2CK  ‐ p. 143 1st chest X-ray can be falsely negative in 10-20% 15 CAP/Diagnostic Tests MTB S2CK  ‐ p. 143 Interstitial infiltrates leave the air space empty. This chest x-ray can be consistent with PCP, Mycoplasma, viruses, and Chlamydia. Source: Craig Thurm, MD CAP/Diagnostic Tests Blood Cultures are positive • 5-15% of CAP • Particularly with S. pneumoniae! MTB S2CK  ‐ p. 143 Sputum Gram stain is “adequate” if: > 25 WBCs and < 10 epithelial cells CAP/Diagnostic Tests Chest CT and MRI show • Greater definition of abnormalities found on chest X-ray But W ’t d t i ifi i bi l i• Won’t determine specific microbiologic etiology In infectious diseases radiologic test is never the most accurate test MTB S2CK  ‐ p. 143 CAP/Diagnostic Tests Tests Done in Severe Disease with an Unclear Etiology, or Those Not Responding to Treatment • Thoracentesis – Any new large effusion should be analyzed Source: nih.gov – Empyema • Infected pleural effusion • Acts like abscess • Only improves if drained with chest tube MTB S2CK  ‐ p. 143 CAP/Diagnostic Tests Transudative Exudative Etiology of pleural effusions Secondary to Secondar toSecondary to • Increased PCWP Or • Decreased intravascular oncotic pressure Secondary to • Increased vascular permeability CAP/Diagnostic Tests • Empyema – LDH > 60% of serum OR – Protein > 50% of serum – pH < 7 2 +gram stain +culture or frank– pH < 7.2, +gram stain, +culture, or frank pus MTB S2CK  ‐ p. 143 New, large effusions secondary to pneumonia should be tapped 16 CAP/Diagnostic Tests • Bronchoscopy – Only needed if sputum stain and culture and blood cultures don’t yield an organism and patient’s condition is worsening despite empiric therapy – Exception is pneumocystis pneumonia MTB S2CK  ‐ p. 143‐144 CAP/Diagnostic Tests • S. pneumo can be tested via urine antigen Mycoplasma pneumoniae Chlamydophila pneumoniae, Chlamydia Specific Diagnostic Tests by Organism Pneumocystis jiroveci (PCP) MTB S2CK  ‐ p. 144 Chlamydia psittaci & Coxiella burnetii • PCR • Cold agglutinins • Serology • Special culture media Rising serologic titers Legionella • Urine antigen, • Culture on charcoal- yeast extract Bronchoalveolar lavage (BAL) CAP/Treatment • Rare to have specific organism identified at time treatment is initiated • If case describes organism on Gram stain treatment is directed towards that organismorganism • Most important step is determining severity of disease. –Determines location in which to place patient MTB S2CK  ‐ p. 144 CAP/Treatment Severity of disease, not the etiology drives initial therapy MTB S2CK  ‐ p. 144 Mycoplasma & Chlamydophila, rarely confirmed because they are simply treated empirically CAP/Treatment Previously healthy or no antibiotics in past 3 months and mild symptoms Comorbidities or antibiotics in past 3 months Outpatient Treatment MTB S2CK  ‐ p. 144 • Macrolide - Azithromycin or clarithromycin Or • Doxycycline Respiratory fluoroquinolone • Levofloxacin Or • Moxifloxacin CAP/Treatment Inpatient Treatment • Respiratory fluoroquinolone: levofloxacin or moxifloxacin Or • Ceftriaxone and azithromycin Almost all infectious diseases are initially treated empirically—that is, without a specific etiology MTB S2CK  ‐ p. 144 17 CAP/Treatment Reasons to Hospitalize • 80% safely treated outpatient with oral antibiotics • Severe disease is defined as a combination of – Hypotension (systolic < 90 mmHg) – Respiratory rate > – Glucose >250 mg/dL – Pulse > 125/min Confusion MTB S2CK  ‐ p. 145 Respiratory rate 30/min – pO2 < 60 mmHg, pH < 7.35 – Elevated BUN > 30 mg/dL, – Sodium 104°F – ≥ 65 or comorbidities such as cancer, COPD, CHF, renal failure, or liver disease CAP/Treatment Hypoxia and hypotension as single factors are a reason to hospitalize a patient MTB S2CK  ‐ p. 145 Chest X-ray does not guide admission cannot tell severity of hypoxia CAP CURB 65 Confusion Uremia Respiratory DistressRespiratory Distress BP low 65-year-old woman is hospitalized with CAP. Sputum Gram stain: Gram-positive diplococci. Sputum culture doesn’t grow a specific organism. Chest X-ray: lobar infiltrate and large effusion. She’s placed on ceftriaxone and azithromycin. Thoracentesis: marked elevated LDH and protein level with 17,000 WBC/μL. Blood cultures grow Streptococcus pneumoniae with minimal inhibitory concentration (MIC) to i illi < 0 1 / L O t ti 96% i BPpenicillin < 0.1 μg/mL. Oxygen saturation 96% on room air. BP 110/70, T 102°F, Pulse 112. What is the next step in management? a. Repeated thoracentesis b. Placement of chest tube for suction c. Add ampicillin to treatment d. Place patient in ICU e. Consult pulmonary MTB S2CK  ‐ p. 145 No need for chest tube Will add nothing Will add nothing No benefit CAP/Treatment MTB S2CK  ‐ p. 146 Pleural effusion with a large meniscus sign. Only a fluid sample from thoracentesis can determine the specific cause. Source: Craig Thurm, MD CAP/Treatment MTB S2CK  ‐ p. 146 Effusion should be freely mobile and from a layer when the patient lies on her side. Source: Nishith Patel. 18 CAP/Treatment MTB S2CK  ‐ p. 146 Hydropneumothorax is both abnormal air and fluid (effusion) in the pleural space. Chest tube drainage is the most effective way to remove this condition. Source: Albert Takem, MD. CAP/Treatment Pneumococcal Vaccination • Everyone > 65 should receive vaccination with 23 polyvalent vaccine • Chronic heart • Liver • Kidney Vaccinated as soon as their underlying disease• Kidney Or • Lung disease – Including asthma MTB S2CK  ‐ p. 146 their underlying disease is apparent, regardless of age CAP/Treatment Pneumococcal Vaccination • Other reasons to vaccinate – Functional or anatomic asplenia (e.g., sickle cell disease) – Hematologic malignancy (leukemia, lymphoma) – Immunosuppression: diabetes mellitus, alcoholics, corticosteroid users, AIDS or HIV positive – CSF leak and cochlear implantation recipients MTB S2CK  ‐ p. 146‐147 CAP/Treatment Pneumococcal Vaccination • Generally healthy: single dose at 65 • If first vaccination was given before 65 or with other conditions previously described a second dose should alsodescribed, a second dose should also be given 5 years after first dose MTB S2CK  ‐ p. 147 Healthcare workers do not need pneumococcal vaccine Pneumonia – Part 2 Healthcare‐Associated Pneumonia or  Hospital‐Acquired Pneumonia (HAP)/Definition • Pneumonia developing > 48 hours after admission • Much higher incidence of Gram-g negative bacilli such as E. coli or Pseudomonas MTB S2CK  ‐ p. 147 19 HAP/Treatment • Main difference in management is – Macrolides (azithromycin or clarithromycin) are unacceptable as empiric therapy • Centered around therapy for Gram-negative bacilli – Antipseudomonal cephalosporins: cefepime or ceftazidime Or – Antipseudomonal penicillin: piperacillin/tazobactam Or – Carbapenems: imipenem, meropenem, or doripenem MTB S2CK  ‐ p. 147 HAP/Treatment Piperacillin and ticarcillin always used in combination with beta-lactamase inhibitor (e.g., tazobactam or MTB S2CK  ‐ p. 147 ( g clavulanic acid) Ventilator‐Associated Pneumonia/Definition • Mechanical ventilation interferes with normal mucociliary clearance of respiratory tract (e.g., ability to cough) • Positive pressure is tremendously damaging to normal ability to clear colonization • Ventilator-associated pneumonia (VAP) has an incidence as high as 5% per day in first few days on ventilator MTB S2CK  ‐ p. 147 VAP/Diagnosis • Because of multiple countercurrent illnesses (e.g., CHF) even a diagnosis of VAP can be hard to establish • Look for – Fever and/or rising WBC count– Fever and/or rising WBC count – New infiltrate on chest X-ray – Purulent secretions coming from endotracheal tube MTB S2CK  ‐ p. 147 VAP/Diagnostic Tests • Sputum culture: nearly worthless – Due to colonization of endotracheal tube (ET) • Diagnosis of specific etiology is extremely difficult on ventilatorextremely difficult on ventilator MTB S2CK  ‐ p. 148 VAP/Diagnostic Tests Tracheal aspirate Suction catheter l d i t ET d Bronchoalveolar lavage (BAL) • Bronchoscope placed deeper in lungs Protected brush specimen • Tip of bronchoscope Least accurate but easiest to do Most accurate but dangerous MTB S2CK  ‐ p. 148 placed into ET and aspirates contents below trachea when catheter is past end of tube deeper in lungs where there aren’t supposed to be organisms • Can be contaminated when passed through the nasopharynx p covered when passed through nasopharynx, then uncovered only inside lungs • Much more specific, decreased contamination 20 VAP/Diagnostic Tests MTB S2CK  ‐ p. 148 Subcutaneous emphysema is air abnormally leaking into soft tissue of the chest wall. Chest tube placement may cause air to leak into soft tissues of the chest wall. Source: Birju Shah, MD. VAP/Treatment 1. Antipseudomonal beta-lactam • Cephalosporin (ceftazidime or cefepime) Or • Penicillin (piperacillin/tazobactam) Or • Carbapenem (imipenem, d i ) Combine 3 different drugs PLUS MTB S2CK  ‐ p. 148‐149 meropenem, or doripenem) 2. Second anti- pseudomonal agent • Aminoglycoside (gentamicin or tobramycin or amikacin) 3. Methicillin-resistant antistaphylococcal agent • Vancomycin Or • Linezolid PLUS VAP/Treatment Change initial therapy for VAP if specific etiology is identified MTB S2CK  ‐ p. 149 Patient hospitalized for head trauma and subdural hematoma is intubated for hyperventilation and subsequent craniotomy. Several days after admission hematemesis ensues and stomach stress ulcers are found. Lansoprazole is started. VAP develops, placed on imipenem, linezolid, and gentamicin. Phenytoin, started prophylactically. Three days later creatinine rises followed by seizures . Repeat head CT shows no hchanges. What is the most appropriate next step in management? a. Switch phenytoin to carbamazepine b. Stop lansoprazole c. Stop imipenem d. Stop linezolid e. Perform an electroencephalogram MTB S2CK  ‐ p. 149  Less likely to cause renal failure (RF)Not likely to cause RF Not likely to cause RF Will add nothing Lung Abscess/Etiology • Rare because of prompt treatment of aspiration pneumonia • Occurs only with Large ol me aspiration of oral/phar ngeal– Large-volume aspiration of oral/pharyngeal contents, usually with poor dentition, who isn’t adequately treated MTB S2CK  ‐ p. 149 Lung Abscess/Etiology • Large-volume aspiration occurs from – Stroke with loss of gag reflex – Seizures – Intoxication – Endotracheal intubation– Endotracheal intubation MTB S2CK  ‐ p. 149 Aspiration pneumonia happens in the right upper lobe when lying flat 21 Lung Abscess/Presentation • Look for – Person with one of these risk factors presenting a chronic infection developing over several weeks with large-volume sputum that is foul smelling because of anaerobes • Weight loss is common MTB S2CK  ‐ p. 150 Lung Abscess/Diagnostic Tests • “Best initial test”: chest X-ray – Cavity, possibly with air-fluid level • Chest CT is more accurate • Only lung biopsy can establish specific microbiologic etiology MTB S2CK  ‐ p. 150 Sputum culture is the wrong answer for diagnosing a lung abscess. Everyone’s sputum has anaerobes from mouth flora. Lung Abscess/Diagnostic Tests MTB S2CK  ‐ p. 150 Cavity consistent with an abscess with a thick wall and an air-fluid level. Source: Alejandro de la Cruz, MD. Lung Abscess/Treatment • Clindamycin is best to cover lung abscess MTB S2CK  ‐ p. 150 Pneumocystis Pneumonia (PCP)/Etiology • Agent causing PCP has been renamed P. jiroveci instead of P. carinii • Almost exclusively in patients with AIDS whose CD4 cell count is < 200/μL and who aren’t on prophylactic therapywho aren t on prophylactic therapy – Also occurs in chronically immunosuppressed patients, especially those on long term high dose steroids MTB S2CK  ‐ p. 150 PCP/Presentation • Look for – Patient with AIDS presenting with dyspnea on exertion, dry cough, and fever • Question will often suggest or directly• Question will often suggest or directly state that CD4 count is low (< 200/μL) and that patient isn’t on prophylaxis MTB S2CK  ‐ p. 150 22 PCP/Diagnostic Tests • “Best initial test” – Chest X-ray showing bilateral interstitial infiltrates Or – ABG looking for hypoxia or an increasedABG looking for hypoxia or an increased A-a gradient • LDH levels are always elevated • “Most accurate test” – Bronchoalveolar lavage MTB S2CK  ‐ p. 150 PCP/Diagnostic Tests • Sputum stain: quite specific if it’s positive – If positive, there is no need to do further testing – If negative, bronchoscopy as “the best diagnostic test” Normal LDH means DON’T answer PCP as “the most likely diagnosis” MTB S2CK  ‐ p. 150‐151 PCP/Diagnostic Tests S2CK asks what is “the most likely diagnosis,” not what is “the for sure diagnosis” MTB S2CK  ‐ p. 151 Cannot distinguish PCP from Mycoplasma, Chlamydophila, or viruses by X-ray alone. However, in HIV, PCP is “most likely” with interstitial infiltrates PCP/Treatment • “Best initial therapy” for both treatment and prophylaxis – Trimethoprim/sulfamethoxazole (TMP/SMX) • Add steroids to decrease mortality if PCP is severe • Severe PCP: pO2 < 70 or A-a gradient > 35 • Atovoquone – Alternative to TMP/SMX if mild PCP, meaning there is g only mild hypoxia • If toxicity from TMP/SMX switch to either – Clindamycin and primaquine Or – Pentamidine MTB S2CK  ‐ p. 151 HIV-positive African American man is admitted with dyspnea, dry cough, high LDH, and pO2 of 63 mmHg. He is started on TMP/SMX and prednisone. On 3rd hospital day he develops severe neutropenia and rash. He has anemia and smear shows bite cells. What is the most appropriate next step in management? a. Stop TMP/SMX b. Begin antiretroviral medications c. Switch TMP/SMX to intravenous pentamidine d. Switch TMP/SMX to aerosol pentamidine e. Switch TMP/SMX to clindamycin and primaquine MTB S2CK  ‐ p. 151  Will not help acute opportunistic infection Need to treat IV for active disease Contraindicated due to G6PD PCP/Treatment Often students will see 2 correct treatments and think there’s a mistake in the question If there are 2 correctthe question. If there are 2 correct treatments, look for a contraindication to one of them. MTB S2CK  ‐ p. 152 23 PCP/Prophylaxis 1. TMP/SMX • Rash Or • Neutropenia AIDS with CD4 count < 200/μL 2. Atovoquone or Dapsone • Aerosol pentamidine: not used as second-line therapy for prophylaxis – Due to less efficacy than either atovoquone or dapsone MTB S2CK  ‐ p. 152 PCP/Treatment • Always choose therapy based first on efficacy, not adverse effects MTB S2CK  ‐ p. 152 Dapsone is contraindicated in those with G6PD deficiency HIV-positive woman with 22 CD4 cells/μL is admitted with PCP and is treated successfully with TMP/SMX. Prophylactic TMP/SMX and azithromycin are started. She is then started on antiretroviral medication and her CD4 rises to 420 cells for last 6 months. What is the most appropriate next step in management? a. Stop TMP/SMX And azithromycin because ↑CD4pb. Stop both TMP/SMX and azithromycin c. Stop all medications and observe d. Stop all medications if the PCR-RNA viral load is undetectable e. Continue all the medications f. Stop the azithromycin MTB S2CK  ‐ p. 152  y ↑Cannot stop antiretrovirals; CD4 will ↓ CD4 will ↓; antiretrovirals maintain CD4 No prophylaxis needed And TMP/SMX because ↑CD4 Tuberculosis Tuberculosis (TB)/Etiology • Due to Mycobacterium tuberculosis • Initial infection most commonly leads to latent TB • Most symptomatic cases due to R ti ti f l t t i f ti th–Reactivation of latent infection rather than primary exposure • Pulmonary TB most common, but can affect any organ system MTB S2CK  ‐ p. 152 Tuberculosis/Etiology • Almost all patients with TB have 1+ established risk factors – Recent immigrants (in past 5 years) – Prisoners – HIV positive – Healthcare workers – Close contact of someone with TB – Steroid use – Hematologic malignancy – Alcoholics – Diabetes mellitus MTB S2CK  ‐ p. 153 24 Tuberculosis/Presentation • Look for – Previously listed risk factors presenting with fever, cough, sputum, weight loss, hemoptysis, and night sweats • Symptoms are almost always > 3 weeks in duration MTB S2CK  ‐ p. 153 You cannot answer TB as diagnosis without a clear risk factor, a cavity on chest X-ray or a positive smear Tuberculosis/Diagnostic Tests • “Best initial test”: chest X-ray as with all respiratory infections • Sputum stain and culture specifically for acid-fast bacilli (mycobacteria) must be done 3 times to fully exclude TB • If 3 negative acid-fast stains, but clinical suspicion g , p high – Bronchoscopy with BAL or pleural biopsy PPD skin testing is never best test for TB in symptomatic patient MTB S2CK  ‐ p. 153‐154 Tuberculosis/Diagnostic Tests • Most common finding: cavitary upper lobe infiltrate MTB S2CK  ‐ p. 153 Chest x-ray with upper lobe disease consistent with TB. Source: Craig Thurm, MD. Tuberculosis/Treatment • Smear positive: begin therapy with 4 drugs – Rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) • Ethambutol not needed if known from start of therapy that organism is sensitive to all TB medications – Ethambutol: given as part of 4-drug empiric therapy prior to knowing sensitivity of organism • After using RIPE for first 2 months – Stop ethambutol and pyrazinamide And – Continue rifampin and isoniazid for next 4 months MTB S2CK  ‐ p. 154 Tuberculosis/Treatment • Standard of care: 6 months total of therapy • Treatment is extended to 9 months for – Osteomyelitis Miliary tuberculosis– Miliary tuberculosis – Meningitis – Pregnancy or any other time pyrazinamide isn’t used MTB S2CK  ‐ p. 154 Tuberculosis/Treatment Toxicity of Therapy • All TB medications cause hepatoxicity • Don’t stop them unless transaminases i 3 5 ti li it f lrise 3-5 times upper limit of normal MTB S2CK  ‐ p. 154 25 Adverse Effects of Antituberculosis Therapy Red color to body secretions Rifampin Peripheral neuropathy Isoniazid Hyperuricemia Pyrazinamide Optic neuritis/ color i i Ethambutol Toxicity MTB S2CK  ‐ p. 154 None, benign finding Use pyridoxine to prevent No treatment unless symptomatic vision Decrease dose in renal failure Treatment Tuberculosis/Treatment Use of Steroids • Glucocorticoids decrease risk of constrictive pericarditis in those with pericardial involvement • Decrease neurologic complication in TB meningitis MTB S2CK  ‐ p. 154 Pregnant patients shouldn’t receive pyrazinamide Latent Tuberculosis/PPD Testing Indications for PPD Testing • Not a general screening test for whole population • Only those in risk groups previously described should be screeneddescribed should be screened • PPD testing isn’t useful in those who are symptomatic or those with abnormal chest X-rays MTB S2CK  ‐ p. 154 Latent Tuberculosis/PPD Testing What Is Considered a Positive Test? • Only induration is counted towards a positive test • Erythema is irrelevant • Induration > 5 mm – HIV-positive patients Glucocorticoid users– Glucocorticoid users – Close contact with active TB patients – Abnormal calcifications on chest X-ray – Organ transplant recipients MTB S2CK  ‐ p. 155 Latent Tuberculosis/PPD Testing • Induration > 10 mm – Recent immigrants (past 5 years) – Prisoners – Healthcare workers – Close contacts with TB patients – Hematologic malignancy alcoholics DMHematologic malignancy, alcoholics, DM • Induration > 15 mm – Those with no risk factors MTB S2CK  ‐ p. 155 Everyone with a reactive PPD test should have a chest X-ray to exclude active disease Latent Tuberculosis/PPD Testing Two-Stage Testing • If patient never had a PPD skin test before, a second test is indicated within 1-2 weeks if first test is negative – 1st test maybe falsely negative • If 2nd test is negative: truly negativeIf 2 test is negative: truly negative • If 2nd test is positive: first test was false negative MTB S2CK  ‐ p. 155 If the first test is positive, a second test isn’t necessary 26 Latent Tuberculosis/PPD Treatment Treatment for a Positive PPD • After active TB has been excluded with a chest X-ray, patients should receive 9 months of isoniazid • Positive PPD confers a 10% lifetime risk of TB • Isoniazid results in 90% reduction in risk; after isoniazid lifetime risk of TB goes from 10% to 1% MTB S2CK  ‐ p. 155 Latent Tuberculosis/PPD Treatment • Those at high risk (e.g., healthcare workers), should have a PPD annually to screen for conversion • Majority of risk for developing active TB lies within first 2 years after conversion MTB S2CK  ‐ p. 155 Once PPD is positive, it’ll always be positive in future Latent Tuberculosis/PPD Treatment PPD testing is one of the hardest and most misunderstood tests on USMLE S2 CK. Reread preceding section and forget what you’ve learned in the past. MTB S2CK  ‐ p. 155 Previous BCG has no effect on these recommendations. If PPD is positive, the patient must take isoniazid for 9 months even if he or she had BCG. Solitary Pulmonary Nodule &  Interstitial Lung Disease Solitary Pulmonary Nodule • For Step 2, be sure to know when biopsy is appropriate! Qualities of Benign and Malignant Pulmonary Nodules Benign  40 years old Enlarging MTB S2CK  ‐ p. 156 Nonsmoker Smooth border Small,  2 cm Atelectasis Adenopathy (+) Sparse, eccentric calcification Abnormal PET scan Solitary Pulmonary Nodule Best initial step in all lung lesions is to compare size with old X-rays Biopsy all enlarging lung lesions, particularly if they are rapidly enlarging • However, doubling in size < 30 days more likely to be infectious than malignant (think about clinical scenario to decide) MTB S2CK  ‐ p. 156 p y y p y g g 27 Solitary Pulmonary Nodule Source: Lange123 at the German language Wikipedia, commons.wikimedia.org High Probability Lesions/Management • When many features are described under “malignant” – Resect (remove) lesion – Sputum cytology, needle biopsy, and PET scanning shouldn’t be done because a ti t t i lik l f l tinegative test is likely false negative • If “resection” is one of the choices, then it’s the answer MTB S2CK  ‐ p. 156 Intermediate Probability Lesions/ Management • There are some “gray” or inconclusive aspects of solitary pulmonary nodule such as – Age range gap (between 30 and 40) Or – Size (between 1 cm and 2 cm) ( ) • Definition of “intermediate probability” MTB S2CK  ‐ p. 156 Intermediate Probability Lesions/ Management • Sputum cytology – If positive, this is highly specific, the “most appropriate next step in management” is resection of lesion – If negative cytology doesn’t exclude malignancy • Bronchoscopy or transthoracic needle biopsy – Each is “the most appropriate next step” in most patients with intermediate probability of malignancy – Bronchoscopy for central lesions – Transthoracic biopsy for peripheral lesions MTB S2CK  ‐ p. 156 Intermediate Probability Lesions/ Management Diagnostic test question in intermediate lesions; clear answer must be present. Choice of test may not be clear, but adverse effects are always clear Mostadverse effects are always clear. Most common adverse effect of a transthoracic biopsy is pneumothorax. MTB S2CK  ‐ p. 157 Intermediate Probability Lesions/ Management Positron emission tomography (PET scan) • Tells whether content of lesion is malignant without biopsy • Malignancy has increased uptake of tagged glucoseglucose • Sensitivity of PET scan is 85 - 95% • Negative scan points away from malignancy MTB S2CK  ‐ p. 157 28 Intermediate Probability Lesions/ Management Video-assisted thoracic surgery (VATS) • VATS is both more sensitive and more specific than all other forms of testing • Frozen section in operating room allows for immediate conversion to an open thoracoscopy and lobectomy if malignancy is found MTB S2CK  ‐ p. 157 Solitary Pulmonary Nodule • Benign pulmonary nodules often represent scar from previous infection – Immigrant, think TB – SW United States, think coccidioidomycosisy – Ohio River Valley, think histoplasmosis Interstitial Lung Disease/Definition • Diseases characterized by inflammation and/or fibrosis of interalveolar septum Fibrosis causes • Impaired gas exchange • Increased lung stiffness And • Decreased lung compliance & expansion MTB S2CK  ‐ p. 157 Source: Ed Uthman. commons.wikimedia.org Interstitial Lung Disease/Etiology Specific Causes of Interstitial Lung Disease • Idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonias • Collagen vascular disease • Granulomatous disorders • Hypersensitivity disorders• Hypersensitivity disorders • Pneumoconiosis • Radiation • Drugs: bleomycin, busulfan, amiodarone, methylsergide, nitrofurantoin, cyclophosphamide MTB S2CK  ‐ p. 157 Interstitial Lung Disease/Etiology Types of Pneumoconioses Exposure Coal Sandblasting, rock  mining, tunneling Shipyard workers, pipe  Disease Coal worker’s pneumoconiosis Silicosis Asbestosis MTB S2CK  ‐ p. 157 py , p p fitting, insulators Cotton Electronic manufacture Moldy sugar cane Byssinosis Berylliosis Bagassosis Biopsy shows granulomas in berylliosis Interstitial Lung Disease/Presentation • All forms of pulmonary fibrosis, regardless of etiology, present with – Dyspnea worsening on exertion – Hypoxia worsening on exertion – Fine rales or “crackles” on examination – Loud P2 heart sound (if pulmonary HTN present) – Clubbed fingers MTB S2CK  ‐ p. 158 Inflammatory infiltration with white cells is reversible (treatable), whereas fibrosis is irreversible 29 Interstitial Lung Disease/Diagnostic Tests  • “Best initial test”: always chest X-ray • High resolution CT scan is more accurate than chest X-ray • “Most accurate test”: lung biopsy E h di h ill ft h• Echocardiography will often show pulmonary HTN and possibly right ventricular hypertrophy MTB S2CK  ‐ p. 158 Interstitial Lung Disease/Diagnostic tests  PCP. Source: commons.wikimedia.org Interstitial Lung Disease/Diagnostic tests  MTB S2CK  ‐ p. 158 Severe, long-standing interstitial fibrosis produces thick walls between alveoli that give the appearance of “honeycombing.” Source: Craig Thurm, MD. Interstitial Lung Disease/Diagnostic Tests  PFTs • Restrictive lung disease with proportional decrease • FEV1, FVC, TLC, and RV all , but since everything is decreased, the FEV1/FVC ratio will be normalbe normal DLCO • Decreased in proportion to severity of alveolar septal thickening MTB S2CK  ‐ p. 158 Interstitial Lung Disease/Treatment  • Most types of interstitial lung diseases are untreatable • Biopsy shows – White cell or inflammatory infiltrate; prednisone should be used – Mostly fibrosis (e.g., IPF), steroids typically NOT y ( g ) yp y effective • Of all causes of pneumoconioses, berylliosis is most likely to respond to steroids – Due to granulomas (sign of inflammation) MTB S2CK  ‐ p. 158 Interstitial Lung Disease/ Hypersensitivity Pneumonitis • Specific type of interstitial lung disease caused by pulmonary hypersensitivity reaction to certain environmental antigens • Inflammation from hypersensitivity reaction results in alveolar thickening and granuloma formation MTB S2CK  ‐ p. 158 30 Interstitial Lung Disease/ Hypersensitivity Pneumonitis Presentation • Acutely – Fever, dyspnea, severe cough – Within 4-6 hours of antigen exposure Or • Chronically – Progressive dyspnea on exertion, fine rales, pulmonary fibrosis Interstitial Lung Disease/ Hypersensitivity Pneumonitis • Most common antigens causing hypersensitivity pneumonitis include – Antigens from feathers (“bird fancier’s lung”) – MAI antigen (“hot tub lung”) – Spores of actinomyces from moldy hay (“farmer’s l ”)lung”) – Spores of actinomyces from compost (“mushroom worker’s lung”) – Spores of actinomyces from air conditioners (“air conditioner lung”) Interstitial Lung Disease/ Hypersensitivity Pneumonitis Treatment • Corticosteroids help to reduce inflammation • AVOID ONGOING EXPOSURE to O O GO G OSU to inciting agent Sarcoidosis &  Thromboembolic Disease Sarcoidosis/Definition/Etiology • More common in African American women • Idiopathic inflammatory disorder predominantly of lungs but can affectpredominantly of lungs, but can affect most of the body • Characterized by noncaseating granulomas MTB S2CK  ‐ p. 159 Sarcoidosis/Presentation • Look for – Young African American woman with SOB on exertion and occasional fine rales on lung exam, but without wheezing of asthma • Erythema nodosum and lymphadenopathy on y y p p y chest X-ray hands you diagnosis question MTB S2CK  ‐ p. 159 31 Sarcoidosis/Presentation • Also presents with – Constitutional symptoms: fever, malaise, weight loss – Arthritis – Parotid gland enlargement Facial pals– Facial palsy – Heart block and restrictive cardiomyopathy – CNS involvement – Iritis and uveitis MTB S2CK  ‐ p. 159 Sarcoidosis/Presentation Brain complications Eye problems (burning, itching, tearing or pain) Salivary glands Enlarged lymph nodes in neck & chest Heart complications Granulomas (inflamed lumps in lungs) Liver enlargement Spleen enlargement Lupus pernio (painful skin sores on face) Skin lesions on back, arms, neck, face, and scalp Enlarged lymph nodes in chest near Erythema nodosum (itchy and painful rashes) on the lower legs and ankles windpipe and lungs Scarring and granulomas in lung Source: National Heart, Lung, and Blood Institute, commons.wikimedia.org Sarcoidosis/Presentation Answer sarcoidosis when chest X-ray or CT shows hilar adenopathy in generally healthy African American woman MTB S2CK  ‐ p. 159 Although liver and kidney granulomas are very common on autopsy, they are rarely symptomatic Sarcoidosis/Diagnostic Tests Chest X-ray: “best initial test” • Hilar lymphadenopathy > 95% with sarcoidosis • Parenchymal involvement can also be present in combination with lymphadenopathy – CXR can reveal bilateral hilar lymphadenopathy only– CXR can reveal bilateral hilar lymphadenopathy only – Hilar lymphadenopathy with parenchymal disease Or – Parenchymal disease alone (depending on stage of disease) MTB S2CK  ‐ p. 159 Sarcoidosis/Diagnostic Tests Source: Jmh649, commons.wikimedia.org Sarcoidosis/Diagnostic Tests • Lymph node biopsy: “most accurate test” – Granulomas are noncaseating • Elevated ACE level: 60% • Hypercalciuria: 20% • Hypercalcemia: 5% yp – Granulomas in sarcoidosis make vitamin D • PFTs: restrictive lung disease – Decreased FEV1, FVC, and TLC with a normal FEV1/FVC ratio MTB S2CK  ‐ p. 159 32 Sarcoidosis/Treatment • Prednisone: drug of choice – Few patients fail to respond • Asymptomatic hilar adenopathy doesn’t need to be treatedneed to be treated MTB S2CK  ‐ p. 159 Thromboembolic Disease/Definition • Pulmonary emboli (PE) and deep venous thrombosis (DVT) are treated as same disease PE • From DVT vessels of legs in 70% of cases and pelvic veins in 30%, but since risks and treatment are the same they can be discussed simultaneously MTB S2CK  ‐ p. 160 Thromboembolic Disease/Etiology • Virchow’s triad outlines conditions that predispose to venous TE • Immobility • CHF • Recent surgery T MTB S2CK  ‐ p. 160 • Factor V Leiden mutation • Any malignancy leads to DVT • Trauma • Surgery • Recent fracture Thromboembolic Disease/Presentation Look for • Sudden onset SOB with clear lungs on examination and normal chest X-ray Other findings in PE – Tachypnea, tachycardia, cough, and hemoptysis – Leg pain from DVTLeg pain from DVT – Pleuritic chest pain from lung infarction – Fever can arise from any cause of clot or hematoma – Extremely severe emboli will produce hypotension MTB S2CK  ‐ p. 160 Thromboembolic Disease/Diagnostic Tests Most questions about PE concern diagnostic testing and treatment • There is no single, uncomplicated diagnostic test for PE • Chest X-ray, EKG, and ABG are best initial tests y, , In PE, the main issue is to know “What’s the most common finding?” And “What’s the most common abnormality when there’s an abnormality?” MTB S2CK  ‐ p. 160 Thromboembolic Disease/Diagnostic Tests Chest X-ray • Usually normal in PE • Most common abnormality is atelectasis • Wedge-shaped EKG • Usually shows sinus tachycardia • Most common abnormality is nonspecific ST-T wave Wedge shaped infarction (Hampton hump), and oligemia of one lobe (Westermark sign) are much less common than simple atelectasis p changes • Only 5% will show right axis deviation, RV hypertrophy or RBBB MTB S2CK  ‐ p. 160‐161 33 Thromboembolic Disease/Diagnostic Tests ABG • Hypoxia and respiratory alkalosis ( pH and  p CO2) with normal chest X-ray is extremely suggestive of PE MTB S2CK  ‐ p. 161 Frequent wrong answer is to choose S1, Q3, T3 as the most common abnormality on EKG 65-year-old woman with recent hip replacement has acute onset of SOB and tachycardia. Chest X-ray normal. Hypoxia on ABG, increased A-a gradient, EKG with sinus tachycardia. What is the most appropriate next step in management? a. Intravenous unfractionated heparin b. Thrombolytics I f i filt  Hemodynamically unstable & acute RV failure Anticoagulants contraindicated,c. Inferior vena cava filter d. Embolectomy e. Spiral CT scan f. Ventilation/perfusion (V/Q) scan g. Lower-extremity Doppler studies h. D-dimer MTB S2CK  ‐ p. 161 Anticoagulants contraindicated, recurrent emboli & RV dysfunction If heparin ineffective & persistent hypotension, hypoxia, tachycardia If initial labs suggestive, treat! Don’t wait to confirm PE Poor specificity Thromboembolic Disease/Diagnostic Tests Spiral CT scan • Also called CT angiogram • Standard of care in diagnostic testing to confirm presence of PE after X-ray, EKG and ABGEKG, and ABG • Specificity is excellent (> 95%) • However, sensitivity is 85%, it can miss 15% of clots MTB S2CK  ‐ p. 161 Thromboembolic Disease/Diagnostic Tests Chest spiral CT scan with radiocontrast agent showing multiple filling defects both at the bifurcation and in the pulmonary arteries. Source: James Heilman, MD, commons.wikimedia.org Thromboembolic Disease/Diagnostic Tests Ventilation/Perfusion (V/Q) scan • May reveal segmental areas of mismatch • High probability scans have no clot (false positive) in 15% • Low probability scans have a clot (false negative) in 15%15% • Interpret results in combination with clinical suspicion MTB S2CK  ‐ p. 161‐162 Chest X-ray must be normal for V/Q scan to have any degree of accuracy. Do a spiral CT if chest X-ray is abnormal. Thromboembolic Disease/Diagnostic Tests MTB S2CK  ‐ p. 161 V/Q or ventilation perfusion scanning is still very useful in evaluating pulmonary emboli. A positive test is an area that is ventilated with decreased perfusion. Source: Nishith Patel. 34 Thromboembolic Disease/Diagnostic Tests D-dimer • Test is very sensitive (better than 97% negative predictive value) • Specificity poor. Any clot or bleeding elevates D-dimer level • Negative test excludes clot • Positive test doesn’t mean anything MTB S2CK  ‐ p. 162 Thromboembolic Disease/Diagnostic Tests D-dimer is answer when pretest probability of PE is low and you need a simple, noninvasive test to exclude thromboembolic disease MTB S2CK  ‐ p. 162 Thromboembolic Disease/Diagnostic Tests Lower extremity (LE) Doppler study • If LE Doppler positive, no further testing needed • Only 70% of PEs originate in legs, so it’ll miss 30% of cases • You don’t need a spiral CT or V/Q scan to confirm a PE if there’s a clot in legs because they won’tPE if there s a clot in legs because they won t change therapy • Patient still needs heparin and 6 months of warfarin MTB S2CK  ‐ p. 162 Thromboembolic Disease/Diagnostic Tests • Spiral CT negative → V/Q or LE Doppler → negative → withhold therapy with heparin LE D l d if MTB S2CK  ‐ p. 162 LE Dopplers are a good test if V/Q and spiral CT do not give clear diagnosis Thromboembolic Disease/Diagnostic Tests Angiography • “Most accurate test” • Nearly 100% specificity and a false negative rate < 1% • Unfortunately, there’s 0.5% mortality, which is high if you consider the tens of thousands of testshigh if you consider the tens of thousands of tests a year that are needed to exclude PE in all cases MTB S2CK  ‐ p. 162 When testing for PE, angiography is rarely done Thromboembolic Disease/Diagnostic Tests Thrombus (labeled A) causing a central obstruction in the left main pulmonary artery. ECG tracing shown at bottom. Source: Aung Myat and Arif Ahsan, commons.wikimedia.org 35 Thromboembolic Disease/Treatment Heparin • “Best initial therapy” • Warfarin should be started simultaneously with heparin to Achie e therape tic INR of 2 to 3 times– Achieve therapeutic INR of 2 to 3 times normal as quickly as possible MTB S2CK  ‐ p. 162 Thromboembolic Disease/Treatment When is an inferior vena cava (IVC) filter the right answer? • Contraindication to the use of anticoagulants (e.g., melena, CNS bleeding) • Recurrent emboli while on heparin or fully therapeutic warfarin (INR of 2–3) • Right ventricular (RV) dysfunction with an enlarged RV on echo. In this case, the next embolus, even if seemingly small, could be potentially fatal MTB S2CK  ‐ p. 162 Thromboembolic Disease/Treatment When are thrombolytics the right answer? • Hemodynamically unstable patients (e.g., hypotension and tachycardia) • Acute RV dysfunction • Contraindicated in patients with recent p surgery or bleeding MTB S2CK  ‐ p. 162 No specific time limit in which to use thrombolytics as there is in stroke or MI Thromboembolic Disease/Treatment When are direct-acting thrombin inhibitors (argatroban, lepirudin) the answer? • Heparin-induced thrombocytopenia When is aspirin the answer? MTB S2CK  ‐ p. 162‐163 When is aspirin the answer? • Never Pulmonary Hypertension,  Obstructive Sleep Apnea, &  Acute RespiratoryAcute Respiratory  Distress Syndrome Pulmonary Hypertension/Definition • Lung or pulmonary circulation normally extremely low pressure – Systolic 25 mmHg – Diastolic 8 mmHg – Mean 15 mmHgMean 15 mmHg MTB S2CK  ‐ p. 163 36 Pulmonary Hypertension/Definition Classified as either • Primary – Idiopathic dysfunction of pulmonary arteries • Secondary causes include – L sided-heart failure (MCC)( ) – Intracardiac L  R shunting – Hypoxic vasoconstriction from chronic lung disease (e.g., COPD) – Thromboembolic disease MTB S2CK  ‐ p. 163 Pulmonary Hypertension/Etiology Chronic hypoxemia leads to pulmonary HTN, which results in more hypoxemia MTB S2CK  ‐ p. 163 Pulmonary Hypertension/Presentation • Dyspnea and fatigue • Syncope (exertional!) • Chest pain (exertional!) • Wide splitting of S2 with loud P2 or tricuspid and pulmonary valve insufficiency • Sign of right sided heart failure• Sign of right-sided heart failure MTB S2CK  ‐ p. 163 It’s impossible to know that pulmonary HTN is causing dyspnea without tests Pulmonary Hypertension/Diagnostic Tests Chest X‐ray and CT • “Best initial tests” • Showing dilation of proximal pulmonary arteries witharteries with narrowing or “pruning” of distal vessels MTB S2CK  ‐ p. 163 Source: tmcr.usuhs.mil Pulmonary Hypertension/Diagnostic Tests Right heart or Swan‐Ganz catheter  • “Most accurate test” And • Most precise Source: commons.wikimedia.org Most precise method to measure pressures MTB S2CK  ‐ p. 163 Pulmonary Hypertension/Diagnostic Tests EKG • Right axis deviation, right atrial and ventricular hypertrophy V/Q scanning • Identifies chronic PE as cause of pulmonary HTN CBC Echocardiography • RA and RV hypertrophy; Doppler estimates pulmonary artery (PA) pressure • Shows polycythemia from chronic hypoxia MTB S2CK  ‐ p. 163 37 Pulmonary Hypertension/Treatment 1. Correct underlying cause when one is clear 2. Idiopathic disease is treated with – Inhaled or intravenous prostacyclin analogues (pulmonary arterial vasodilators): epoprostenol, treprostinil, iloprost, beraprost Endothelin antagonists: bosentan– Endothelin antagonists: bosentan – Phosphodiesterase inhibitors: sildenafil – Calcium-channel blockers • Only if demonstrated to be responsive to them during right heart catheterization MTB S2CK  ‐ p. 164 Pulmonary Hypertension/Treatment • Oxygen slows progression, particularly with COPD Only lung transplantation is MTB S2CK  ‐ p. 164 curative for idiopathic pulmonary HTN Obstructive Sleep Apnea (OSA)/Definition • Cessation of airflow due to upper airway obstruction during sleep Ob it i t• Obesity is most commonly identified cause MTB S2CK  ‐ p. 164 Source: Habib M'henni, commons.wikimedia.org Obstructive Sleep Apnea (OSA)/Presentation • Patients present with daytime somnolence and history of loud snoring • Other symptoms include – Headache Impaired memory and judgment– Impaired memory and judgment – Depression – HTN – Erectile dysfunction MTB S2CK  ‐ p. 164 Obstructive Sleep Apnea • Risk factors include – Male gender – Obesity – Large uvula/tongue And – Retrognathia (recession of mandible)Retrognathia (recession of mandible) • Arrhythmias and erythrocytosis are common • Can lead to pulmonary HTN and RV failure • “Most accurate test” is polysomnography (sleep study) – Shows multiple episodes of apnea MTB S2CK  ‐ p. 164 Obstructive Sleep Apnea/Treatment 1. Weight loss and avoidance of alcohol 2. Nasal continuous positive airway pressure (nasal CPAP) 3. Surgical widening of airway (uvuloplatopharyngoplasty) if this fails(uvuloplatopharyngoplasty) if this fails 4. Avoid use of sedatives MTB S2CK  ‐ p. 164 38 Acute Respiratory Distress Syndrome (ARDS)/ Definition • Acute respiratory failure from overwhelming lung injury or systemic disease Characterized by • Severe hypoxia • Poor lung compliance And • Noncardiogenic pulmonary edema – ARDS is caused by endothelial injury at level of alveolus, making lung cells “leaky” so that alveoli fill up with fluid MTB S2CK  ‐ p. 164‐165 ARDS/Etiology • ARDS is idiopathic • Large number of illnesses and injuries are associated with alveolar epithelial cell and capillary endothelial cell damage • Illnesses and injuries associated with developing ARDS include – Sepsis or aspiration – Lung contusion/trauma – Near-drowning – Burns or pancreatitis MTB S2CK  ‐ p. 165 ARDS/Diagnostic Tests • Chest X-ray shows bilateral infiltrates quickly become confluent (“white out”) • Air bronchograms are common MTB S2CK  ‐ p. 165 ARDS/Diagnostic Tests Source: Samir , commons.wikimedia.org ARDS/Diagnostic Tests MTB S2CK  ‐ p. 165 Air bronchograms are a sign of dense consolidation of the lung air space. This is a case of pneumococcal pneumonia that left only the air space in the larger bronchi open or air bronchograms. Source: Omid Edrission, MD. ARDS/Diagnostic Tests • Defined as having PaO2/FiO2 ratio < 200 – The FIO2 is expressed as a decimal (e.g., room air with 21% oxygen = 0.21) – If pO2 is 105 on room air (21% oxygen or 0.21), then the ratio of pO2/FIO2 is 500 (i.e., 105/.21) – If pO2 (as measured on ABG) is 70 while– If pO2 (as measured on ABG) is 70 while breathing 50% oxygen, the ratio is 70/0.5 or 140 • ARDS is associated with normal findings on right heart catheterization • Wedge pressure is normal (< 18 mmHg) MTB S2CK  ‐ p. 165 39 ARDS/Treatment • Low tidal volume mechanical ventilation is the best support while waiting to see if lungs will recover –Use 6 mL/kg of tidal volume • Steroids aren’t clearly beneficial in• Steroids aren t clearly beneficial in most cases –They may help in late-stage disease in which pulmonary fibrosis develops MTB S2CK  ‐ p. 166 ARDS/Treatment • Positive end-expiratory pressure (PEEP) is used when patient is undergoing mechanical ventilation to  FIO2 • Levels of FIO2 > 50% are toxic to lungs • Maintain plateau pressure < 30 cm of water measured on ventilator MTB S2CK  ‐ p. 166 No treatment is proven to reverse ARDS. Don’t forget to treat the underlying cause. 1 Preventative Medicine Conrad Fischer, MD Associate Professor of Medicine Touro College of Medicine New York City Cancer Screening Breast Cancer Cervical CancerCervical Cancer Colon Cancer Prostate Cancer Lung Cancer • Mammography screening tool of choice • Start at 50 years old – When reward is highest – Starting at 40 is controversial • MRI CT and US are adjuvant screening Breast Cancer Screening MRI, CT, and US are adjuvant screening MTB S2CK – p. 356   Self-examination not recommended. Never the correct answer on S2CK. Which of the following is most likely to benefit an asymptomatic patient with multiple first-degree relatives with breast cancer? a. Tamoxifen b. BRCA testing c Aromatase inhibitors  Most familial breast ca. NOT BRCA Unproven in preventionc. Aromatase inhibitors d. Dietary modification e. HER-2/neu testing f. Estrogen/progesterone receptor testing MTB S2CK – p. 356   Unproven in prevention Effective but to lesser degree Performed in breast cancer patients Performed in breast cancer patients TAMOXIFEN • Greater risk: –DVT/PE and endometrial cancer • Less risk: Fractures• Less risk: Fractures • Remember! –Better to be ALIVE with a DVT than DEAD with normal legs Can STOP mammography at age 75 HER-2/neu positive patients treated with trastuzumab if you HAVE cancer! Not a prophylactic! 2 Cervical Cancer Screening • Papanicolaou test = “Pap Smear” – Start at age 21 – Done every 3 years, with cytology, until 30 years oldyears old – After age 30, if HPV testing added, then every 5 years – Stop at age 65 with adequate screening history and low risk MTB S2CK – p. 357 © Katsumi M. Miyai, M.D., Ph.D., Regents of the University of California. Used with permission. Colon Cancer Screening • Colonoscopy – The most accepted screening test – Start at 50 years – Repeat every 10 years • Exceptions All other testing modalities are inferior to colonoscopy– Family history • 1st-degree relative 40 or ten years earlier • Whichever is EARLIER! • HNPCC: • 3 relatives, 2 generations, 1 premature • Start at 25 and do colonoscopy every 1-2 years MTB S2CK – p. 357 colonoscopy Colon Cancer Screening • Familial Adenomatous Polyposis – Sigmoidoscopy at age 12, then every year • Personal History of Polyps – Repeat every 3-5 yearsp y y Prostate Cancer Screening • There’s no test that reduces mortality • Prostate Specific Antigen (PSA) – Doesn’t reduce mortality – Useful in tracking current disease • Digital Rectal Exam (DRE)Digital Rectal Exam (DRE) – Doesn’t reduce mortality MTB S2CK – p. 357‐358 PSAs require a conversation with the patient regarding pros and cons Lung Cancer Screening • Not recommended at this time • Chest radiograph, CT scan, MRI, PET, etc. – All have their purpose but NOT in screening MTB S2CK – p. 358 Any question asking who and when to screen for lung cancer is a trick Summary of Preventive Medicine Key Points • Mammography >50 to age 75 • Tamoxifen for multiple 1st degree relatives • BRCA is NOT clear! • Pap smear interval to 5 years after age 30, if combined with HPV testingif combined with HPV testing • No lung or prostate screening clearly effective MTB S2CK – p. 358 3 Non‐Cancer Screening and  Prevention Lipid  Screening Hypertension: Diagnosis and Control Diabetes Mellitus Other Screenings Lipid Screening • Different by age and gender – Men start at 35 yo – Women start at 45 yo – Frequency depends on CVD status • What is the test? – Cholesterol panelCholesterol panel • Total CHL, HDL, LDL • LDL guides therapy usually • We do NOT know what to do with Triglycerides! MTB S2CK – p. 358 Lipid Screening • Normal Values? – Determined by what’s tolerable given risk • Interventions – Diet, Exercise, Pharmacology • Goals differ based on comorbidities Diabetes– Diabetes – HTN – Coronary disease or equivalent MTB S2CK – p. 358 Coronary Artery Disease (CAD) “equivalents”: Carotid disease, peripheral arterial disease (PAD), diabetes mellitus, and aortic disease Lipid Screening • Goals of Therapy – HDL Cholesterol > 40 0-1 Risk: – Diet at LDL >160 – Drugs at LDL >190 2 or more risks2 or more risks – Diet at LDL >130 – Drugs at LDL >160 For CAD and Equivalents – LDL Cholesterol < 100 Both diet and drugs • Possibly < 70 for CAD combined with Diabetes! MTB S2CK – p. 358 Hypertension • All adults (>18) should be “screened” at every visit • At least every two years • “HTN” – Elevated BP at ≥ 2 separate occasions – Not clear what to do about “Pre-hypertension” MTB S2CK – p. 358 ~ Diabetes Screening • Who is screened? – Those with CHD – Hypertension is the clearest risk to screen for DM Test Fasting Blood Glucose (FBG) Diabetes ≥ 126 mg/dL MTB S2CK – p. 359 Oral Glucose  Tolerance Test (OGTT) Hemoglobin A1C ≥ 200 mg/dL ≥ 6.5% 4 Osteoporosis • Bone density 2.5 SDs below average • Recommendation – Every woman screened at 65 yo – Dual-Energy X-ray Absorptiometry (DEXA) scan • Osteoporosis  Fractures  Increased Mortality MTB S2CK – p. 361 Other Screenings • Abdominal Aortic Aneurysms – All men – ≥ 65 -75 – ANY smoking history… – Receive abdominal ultrasounds at least once • Tobacco (traditional or smokeless)Tobacco (traditional or smokeless) – Employ the “Five-A’s” – Ask, Advise, Attempt, Assist, Arrange • Intimate Partner Violence – Not to be overlooked MTB S2CK – p. 361 Alcohol Dependence • Alcohol – Know difference between dependence and abuse – “CAGE” Questions • Do they feel the need Cut down? • Do they feel Annoyed with criticism of drinking? • Have they ever felt Guilty by their drinking?• Have they ever felt Guilty by their drinking? • Do they ever need an Eye-opener? MTB S2CK – p. 361‐362 Vaccinations Influenza and PneumococcalInfluenza and Pneumococcal Varicella Hepatitis A & B Tetanus Meningococcal Influenza Vaccination • Influenza A and B – Strains circulating in previous year – Inactivated (killed) injection • Who gets it? – Everybody – Every year – Healthcare workers pregnant women eldersHealthcare workers, pregnant women, elders MTB S2CK – p. 359 INFLUENZA VACCINE Every person Every year Pneumococcal Vaccine • 23-valent Pneumococcal Polysaccharide Vaccine • Protects against Streptococcal pneumoniae • Who gets it? – Chronically ill • Respiratory, heart, kidney, and liver diseases – ImmunocompromisedImmunocompromised • Asplenia – Elderly: ≥ 65 yo • Revaccination after 5 years MTB S2CK – p. 359 5 Varicella & Herpes Zoster Vaccination • Live attenuated vaccine against varicella virus • Who gets “Chicken Pox” vaccination? – ALL adults seronegative for varicella infection • Who gets “Herpes Zoster” vaccination? – ALL adults ≥ 60 yo • Reduces incidence and severity MTB S2CK – p. 360 • Reduces incidence and severity • “Herpes Zoster” vaccine ≠ “Chicken Pox” vaccine – Different strengths and indications Vaccines given to persons ≥ 60 to prevent zoster have 18 times viral antigens of pediatric vaccines Varicella Vaccination © Richard Usatine, M.D. Used with permission. Hepatitis Vaccination Hepatitis A • Fecal‐oral transmission • Infection related to poor  hygiene and crowding • No carrier state • Lowmortality/morbidity Hepatitis B • Percutaneous, perinatal,  and sexual routes • (+) Carrier state • 10% develop chronic  disease MTB S2CK – p. 360 disease Hepatitis A Vaccine Hepatitis B Vaccine • Chronic liver disease • MSM or IV drug users • Infected close contacts • Travelers • Chronic Liver disease • MSM or IV drug users • Infected close contacts • Healthcare workers • Dialysis patients  Hepatitis Vaccination Hepatitis B Vaccine DIABETES is an indication! MTB S2CK – p. 360 Tetanus Vaccine • Tetanus Toxoid booster every 10 years • One Tdap (Tetanus Acellular Pertussus) should be one of them • Five years after a dirty wound MTB S2CK – p. 360 Meningococcal Vaccination • Quadrivalent conjugate polysaccharide vaccine – A,C,Y,W • Very efficacious • Who gets it? – ALL children age 11 Adults:– Adults: • Asplenia or equivalent immunodeficiency • Epidemic settings (military, college dormitories) MTB S2CK – p. 360 6 Epidemiology Sensitivity & SpecificitySensitivity & Specificity Positive and Negative Predictive Values Changing the Cutoff? Important Formulas Important Definitions Prevalence: Total number of diseased patients in the population. Incidence: Number of NEW cases during a specified period of time. Sensitivity (SN): Probability that person with disease has a positive test. Specificity (SP): Positive Predictive Value (PPV): Negative Predictive Value (NPV): Of those with a positive test, what proportion have disease? Of those with a negative test, what proportion do not have disease? Probability that person without disease has a negative test. The 2x2 Table a b c d (+) D (-) D (+) Test (-) Test a b c d a b c dc d( ) est c dc d The 2x2 Table: Sensitivity and Specificity a b c d (+) D (-) D (+) Test (-) Test a b c d a c d( ) est c d Sensitivity (SN): Probability that person with disease has a positive test. = a / (a+c) The 2x2 Table: Sensitivity and Specificity a b c d (+) D (-) D (+) Test (-) Test a b c ddc d( ) est = d / (b+d) Specificity (SP): Probability that person without disease has a negative test. c dd The 2x2 Table: PPV and NPV a b c d (+) D (-) D (+) Test (-) Test a b c d a c d( ) est = a / (a+b) Positive Predictive Value (PPV): Of those with a positive test, what proportion have disease? c d 7 The 2x2 Table: PPV and NPV a b c d (+) D (-) D (+) Test (-) Test a b c ddc d( ) Test = d / (c+d) Negative Predictive Value (NPV): Of those with a negative test, what proportion do not have disease? c dd The 2x2 Table: SN, SP, PPV, NPV a b c d (+) D (-) D (+) Test (-) Test PPV a / (a+b) NPV c d( ) Test d / (c+d) SN a / (a+c) SP d / (b+d) Sensitivity (SN): Specificity (SP): Positive Predictive Value (PPV): Negative Predictive a / (a + b) d / (c + d) a / (a + c) d / (b + d) Formulas List a b c d a cc b d b g Value (NPV): d / (c + d) False Negative Ratio: c / (a + c) or (1 – SN) False Positive Ratio: b / (b + d) or (1 – SP) Epidemiology in Practice Disease No disease Test Cutoff Epidemiology in Practice Disease No disease Test Cutoff Epidemiology in Practice Disease No disease Positive Test Negative Test Test Cutoff 8 Epidemiology in Practice Disease No disease Positive Test Negative Test Test Cutoff Moving the Cutoff Disease No disease Test Cutoff Moving the Cutoff Disease No disease Positive Test Negative Test Test Cutoff Moving the Cutoff Disease No disease Positive Test Negative Test Test Cutoff How does this affect: SP, SN, PPV, NPV ? Positive Test Negative Test Positive Test Disease Negative Test No disease a b c d (+) D (-) D (+)T (-)T a c a b dd a ba c dd Disease No disease SN:    NPV: SP: PPV: Important Epidemiology Concepts • Sensitivity and specificity are independent of disease prevalence – Characteristics of test • PPV and NPV are dependent on disease prevalence 9 Important Epidemiology Concepts • When using a particular test: – Raising the Cutoff • Increases Sensitivity and NPV • Decreases Specificity and PPV – Lowering the Cutoff • Increases Specificity and PPV • Decreases Sensitivity and NPV Sensitivity (SN): Specificity (SP): Positive Predictive Value (PPV): Negative Predictive Value (NPV): a / (a + b) d / (c + d) a / (a + c) d / (b + d) Formulas List False Negative Ratio: c / (a + c) or (1 – SN) False Positive Ratio: b / (b + d) or (1 – SP) Positive Likelihood Ratio: (SN) / (1 – SP) Negative Likelihood Ratio: (1 – SN) / SP Epidemiology Sensitivity & SpecificitySensitivity & Specificity Positive and Negative Predictive Values Changing the cutoff? Important Formulas 1 RADIOLOGY Matthew Kinney, MD Orthopedic Resident University of California San Diego X‐rays • Subjective pulmonary complaints – Cough – SOB/dyspnea – Pleuritic chest pain – Hemoptysis Chest X‐ray Indications  MTB S2CK  ‐ p. 491 Chest X‐ray Indications • Objective pulmonary findings – Rales (Crackles) – Rhonchi – Wheezing – Hyperresonance/ yp dullness to percussion – Chest wall tenderness – Tracheal deviation – SVC syndrome • JVD • Plethora MTB S2CK  ‐ p. 491 Source: James Heilman, MD Chest X‐ray Views • Posterior/anterior (PA) films – Standard CXR positioning – Patient must be capable of standing MTB S2CK  ‐ p. 491 Source: commons.wikimedia.org Chest X‐ray Views  • Anterior/posterior (AP) films – Necessary for immobile patients • ICU • Paralysis MTB S2CK  ‐ p. 491 Source: Mikael Häggström 2 Chest X‐ray Views  • Lateral – Useful to localize lesion found on PA films – Most sensitive test for pleural effusion MTB S2CK  ‐ p. 492 Source: Zachary M Alexander Chest X‐ray Views  • Lateral decubitus – Patient lies on side – Useful to evaluate pleural effusions MTB S2CK  ‐ p. 491 Source: Nicholas Lange Chest X‐ray Findings • Lobar pneumonia MTB S2CK  ‐ p. 491 Source: Nicholas Lange Chest X‐ray Findings • Solitary pulmonary nodule MTB S2CK  ‐ p. 491 Source: Zachary M Alexander Chest X‐ray Findings  • Pleural effusion MTB S2CK  ‐ p. 491 Source: James Heilman, MD Source: Magnus Manske Chest X‐ray Findings  • Pneumothorax MTB S2CK  ‐ p. 491 Source: John Yasmer 3 Chest X‐ray Findings  • Free air under diaphragm MTB S2CK  ‐ p. 491 Source: Brian Johnston Abdominal X‐ray Indications • Small bowel obstruction – Mechanical obstruction – Ileus MTB S2CK  ‐ p. 492 Abdominal X‐ray Views • Abdominal plain film – Erect view of abdomen MTB S2CK  ‐ p. 492 Source: Nevit Dilmen Abdominal X‐ray Views  • Kidneys, ureters, and bladder (KUB) – Supine view of abdomen MTB S2CK  ‐ p. 492 Source: Nevit Dilmen Abdominal X‐ray Findings • Small Bowel Obstruction – Mechanical obstruction MTB S2CK  ‐ p. 492 Source: Stephanie A Bernard Air fluid levels Bone X‐ray Indications • Fracture • Bone tumor evaluation • Osteomyelitis • Skeletal Survey – Trauma Child abuse– Child abuse MTB S2CK  ‐ p. 492 Source: James Heilman, MD 4 Bone X‐ray Findings • Osteomyelitis – Periosteal elevation – Osteolysis • Surrounded by ring of sclerosis Note: XR findings are– Note: XR findings are delayed (2 weeks) • MRI is positive earlier MTB S2CK  ‐ p. 492 Source: commons.wikimedia.org Computed Tomography (CT) CT Basics Definition – Computed Tomography • Large series of 2D X-rays around a single axis of rotation to create 3D image – Increased detail clarity – “Windowing” capability Drawbacks • High doses of radiation • Often requires IV contrast – Anaphylaxis risk – Renal damage • Consider 1-2 liters of fluids, NaHCO3, and/or NAC if mild renal insufficiency – Medication contraindications (“metformin”) Non‐contrast Head CT Indications • Severe head trauma – Loss of consciousness – Altered mental status • Stroke – Hemorrhagic – IschemicIschemic • Intracranial bleeding – Subdural hematoma – Epidural hematoma MTB S2CK  ‐ p. 493 Non‐contrast Head CT • Bone - bright white • Blood - bright white • CSF - dark black MTB S2CK  ‐ p. 493 Source: Andrew Ciscel Non‐contrast Head CT Findings Ischemic Stroke • Darkening of brain parenchyma • Blurred Gray-White Junction • Mass effect MTB S2CK  ‐ p. 493 Source: Lucien Monfils 5 Non‐contrast Head CT Findings Hemorrhagic Stroke • Bright, localized area corresponding to bleed • Mass effect • Gray-white junction intact MTB S2CK  ‐ p. 493 Source: James M. Grimson Non‐contrast Head CT Findings Subdural Hematoma • Crescent-shaped, bright white region – Not confined by skull sutures – Adjacent to skullj • Mass effect MTB S2CK  ‐ p. 493 Source: commons.wikimedia.org Non‐contrast Head CT Findings Epidural Hematoma • Biconvex, bright white region – Adjacent to skull – Confined by skull sutures • Mass effect MTB S2CK  ‐ p. 493 Source: Hellerhoff, commons.wikimedia.org Contrast Head CT Indications • Infection – Meningitis – Abscess • Tumor – Primary Cancer – Brain MetastasisBrain Metastasis MTB S2CK  ‐ p. 493 Source: commons.wikimedia.org Contrast Head CT Findings Tumor • Primary tumor: Single lesion – Bright white – Mass effect – Identical to abscess MTB S2CK  ‐ p. 493 Source: James Heilman, MD Contrast Head CT Findings Tumor • Metastasis: Often multiple lesions – Bright white – Found mostly at gray-white junction – Mass effect MTB S2CK  ‐ p. 493 Source: James Heilman, MD 6 Abdominal CT Indications • Retroperitoneal structure pathology – Pancreatitis – Adrenal gland tumors • Appendicitis • Diverticulitis • Nephrolithiasis• Nephrolithiasis • Abdominal viscera masses – Liver tumors • Splenic laceration • NOTE: Use both oral and IV contrast MTB S2CK  ‐ p. 493 Abdominal CT Views MTB S2CK  ‐ p. 493 Source: commons.wikimedia.org Abdominal CT Findings Pancreatitis • Irregular pancreatic outline • Pancreatic enlargement • Retroperitoneal fluid MTB S2CK  ‐ p. 493 Source: James M Grimsom Abdominal CT Findings Appendicitis • Appendix enlargement (> 6mm) • Wall thickening • Fat stranding MTB S2CK  ‐ p. 493 Source: Andrew Sellers  Appendix  dilated to 15  mm that  doesn’t fill with  contrast. Abdominal CT Findings Diverticulitis • Localized bowel wall thickening • Fat stranding • Evidence of diverticulae • Note: If advanced, abscess may be present MTB S2CK  ‐ p. 493 Source: Hellerhoff, commons.wikimedia.org Abdominal CT Findings Nephrolithiasis • Visible calcification in urinary tract • Evidence of hydronephrosis (if obstructing) • Note: No oral or IV contrast MTB S2CK  ‐ p. 493‐494 Source: Phil Kang 7 Chest CT Indications • Mass lesions – Lung – Mediastinum • Lung pathology – Interstitial lung disease – SarcoidosisSarcoidosis – Bronchiectasis – Cavitary lesions • Pulmonary embolism MTB S2CK  ‐ p. 494 Normal Chest CT MTB S2CK  ‐ p. 494 Source: Brendan T Doherty Magnetic Resonance Imaging,  Ultrasonography, & Nuclear  MedicineMedicine MRI Basics • Definition – Magnetic Resonance Imaging 1) Magnetic field aligns H20 molecular dipoles 2) RF waves are applied, which alters proton spin 3) When waves are stopped, the protons relax to their natural spin -- producing a measurable signal – Upshot: Allows visualization of tissue based on water contentcontent • Best test for evaluating soft tissue • Drawbacks – Long scans requiring complete immobility – Certain metal implants are contraindicated – Small bore tubes – claustrophobia + body mass issues MTB S2CK  ‐ p. 494 MRI Indications • CNS pathology – Brain/spinal cord tumors – MS – Specific regions of the head • Sinuses • Orbits • Musculoskeletal disease – Osteomyelitis – Soft tissue injury – Nerve compression • Herniated disc disease • Brachial plexus injury MTB S2CK  ‐ p. 494 MRI Findings Primary Brain Tumor • Contrast enhancing • Solitary lesion • Mass effect MTB S2CK  ‐ p. 494 Source: Steven J. Goldstein 8 MRI Findings Multiple Sclerosis • Contrast-enhanced • Demyelinated plaques appear white MTB S2CK  ‐ p. 494 Source: Jeffery Hirsch MRI Findings Spinal Disc Herniation • Disc extruding from IV space • Compression of spinal cord MTB S2CK  ‐ p. 494 Ultrasonography US Basics • Definition – Ultrasonography – Sound waves of a certain frequency emitted – Echoes return based on specific tissue properties • Dense objects (e.g., stones, tissue) reflect waves better than fluid/air – Scanner measures echoes and creates image based on differences in object densitydifferences in object density • Drawbacks – Poor at visualizing structures beyond bone – Poor at visualizing structures beyond air – Body habitus affects image quality MTB S2CK  ‐ p. 494‐495 US Indications • Gallstone disease • Renal disease – PCKD – Hydronephrosis – Note: CT preferred for kidney stones • Gynecologic evaluationGynecologic evaluation – PCOS – Uterine evaluation – Pregnancy evaluation – Ectopic pregnancy • Pancreatic disease (via endoscopic US) MTB S2CK  ‐ p. 494‐495 US Findings Cholecystitis • Presence of gallstone – Stone in lumen – Silhouette • Gall bladder wall thickening • Pericholestatic fluid • Sonographic Murphy’s sign MTB S2CK  ‐ p. 494‐495 Source: Joseph Lagrew 9 Nuclear Medicine Nuclear Scans Basics Definition • Radiolabeled molecules localize to specific organs • Emission detected and allow for visualization of organ function – PET scan = Glucose– PET scan = Glucose – Cholescintigraphy = HIDA – V/Q scan MTB S2CK  ‐ p. 495 Source: Jeffrey Hirsch Nuclear Scan Types HIDA (Hepatobiliary) scan MTB S2CK  ‐ p. 495 Source: Jonathan Sexton Nuclear Scan Types Ventilation/perfusion (V/Q) scanning MTB S2CK  ‐ p. 495 V���������� P��������Source: Kieran Maher Nuclear Scan Types  • Bone scan – Uptake into osteoblasts – Useful for detecting area of high bone turnover • Occult cancer metastasis • Indium scan – Uptake into WBCs – Useful in detecting fever of unknown origin (FUO) • Gallium scan – Uptake with iron metabolism – Useful for detecting FUO and some cancers • Nuclear Ventriculography – Used to measure cardiac ejection fraction MTB S2CK  ‐ p. 495 1 RHEUMATOLOGY Niket Sonpal, MD Chief Resident Lenox Hill Hospital‐NSLIJ Assistant Clinical Professor ‐ Touro College of Medicine Osteoarthritis, Gout, &  Pseudogout  Osteoarthritis/Definition  • Osteoarthritis or degenerative joint disease (DJD) • Chronic, slowly progressive, erosive damage to joint surfaces • Loss of articular cartilage• Loss of articular cartilage MTB S2CK  ‐ p. 167 Osteoarthritis/Etiology  • Incidence directly proportional to increasing age and trauma to joint –Contact sports with trauma • Obesity increases DJD MTB S2CK  ‐ p. 167 DJD is, by far, the MCC of joint disease. Osteoarthritis/Presentation  • Most commonly symptomatic in weight- bearing joints • Hand is affected, but isn’t as great a cause of disability • Distal interphalangeal (DIP) joints are >• Distal interphalangeal (DIP) joints are > proximal interphalangeal joints (PIP) and metacarpophalangeal joints (MCP) MTB S2CK  ‐ p. 167 Osteoarthritis/Presentation  • Crepitations of involved joints are common • Effusion is rare • Stiffness is of short duration ( 2 Heberden’s nodes (DIP joint) Bouchard’s nodes (PIP joint) Osteoarthritis © Richard Usatine, M.D. Used with permission Osteoarthritis/Diagnostic Tests  Erythrocyte sedimentation rate Normal Lab Tests Antinuclear tib d Complete blood t MTB S2CK  ‐ p. 167 Rheumatoid factor antibody count Osteoarthritis/Diagnostic Tests  Dense subchondral bone X-rays Show: OsteophytesJoint space MTB S2CK  ‐ p. 168 Bone cysts y Osteophytesnarrowing Osteoarthritis Source: Russell A. Patterson Osteoarthritis/Diagnostic Tests  Absence of inflammation, normal lab tests, and short duration of stiffness MTB S2CK  ‐ p. 168 distinguishes DJD from RA Osteoarthritis/Treatment 1. Weight loss and moderate exercise 2. Acetaminophen: best initial analgesic 3. NSAIDs: used if symptoms aren’t controlled with acetaminophen; toxicity - GI bleeding 4. Capsaicin creamp 5. Hyaluronic acid injections 6. Intra-articular steroids 7. Joint replacement MTB S2CK  ‐ p. 168 Glucosamine and chondroitin sulfate are no more effective than placebo. 3 Gout/Definition/Etiology • Defect in urate metabolism • 90% of cases in men • Can be from: – Overproduction or – Underexcretion MTB S2CK  ‐ p. 168 Gout/Etiology Increased cell turnover Overproduction Enzyme deficiencyIdiopathic MTB S2CK  ‐ p. 168 Underexcretion Thiazides or ASA AcidosisRenal Insufficiency Gout/Presentation • Man who develops sudden, excruciating pain, redness, and tenderness of big toe at night after binge drinking with beer • Fever is common • Hard to distinguish initial gouty attack from infection without arthrocentesis • Metatarsal phalangeal (MTP) joint of great toe most frequently affected • Also in ankles, feet, and knees MTB S2CK  ‐ p. 168 Gout © Richard Usatine, M.D. Used with permission. Gout/Presentation Chronic Gout • Tophi: tissue deposits of urate crystals with foreign body reaction • Most often tophi occur in cartilage, subcutaneous tissues, bone, and kidney • Often take years to developOften take years to develop • Uric acid kidney stones occur in 5% to 10% of patients • Long asymptomatic periods between attacks are common MTB S2CK  ‐ p. 169 Tophi can occur anywhere in the body. Gout/Diagnostic Tests • Most accurate test: – Aspiration of joint • Needle-shaped crystals with negative birefringence on polarized light microscopy MTB S2CK  ‐ p. 169 Commons.Wikimedia.org. used with permission 4 Gout/Diagnostic Tests • WBC joint fluid elevated 2,000 to 50,000/μL • Predominantly neutrophils • Infected joint has redness, warmth, and tenderness • It’s essential to tap joint to exclude infection Protein and glucose levels in synovial fluid don’t help answer the “most likely diagnosis” question MTB S2CK  ‐ p. 169 Gout/Diagnostic Tests • Uric acid levels: elevated at some point in 95% of patients • Single level during an acute attack normal in 25% • Acute attacks =  ESR and leukocytosis• Acute attacks =  ESR and leukocytosis MTB S2CK  ‐ p. 169 Gout/Diagnostic Tests X-rays: • Normal in early disease • Erosions of cortical bone happen later MTB S2CK  ‐ p. 169 Source: Wikimedia.org Gout/Treatment Acute Attack • NSAIDs superior to colchicine as “best initial therapy” • Corticosteroids injection: single joint , oral: multiple joints • Steroids (e g triamcinolone) is answer when:Steroids (e.g., triamcinolone) is answer when: – No response to NSAIDs – Contraindication to NSAIDs such as renal insufficiency Contraindication questions are always clear MTB S2CK  ‐ p. 169 Chronic Management 1) Diet • Decrease consumption of alcohol, particularly beer; lose weight • Decrease high-purine foods 2) Stop thiazides, aspirin, and niacin 3) Colchicine is effective at preventing Management second attack of gout 4) Probenecid and sulfinpyrazone increase the excretion of uric acid in kidney (uricosuric) 5) Allopurinol decreases production of uric acid MTB S2CK  ‐ p. 169‐170 Gout/Treatment Colchicine gives diarrhea and bone marrow suppression (neutropenia). MTB S2CK  ‐ p. 170 Probenecid, NSAIDs, and sulfinpyrazone are contraindicated in renal insufficiency. Allopurinol is safe with renal injury. 5 Gout/Treatment Adverse Effects of Chronic Treatment • Hypersensitivity (rash, hemolysis, allergic interstitial nephritis) occurs with uricosuric agents and allopurinol • Colchicine can suppress white cell production • Toxic epidermal necrolysis or Stevens-JohnsonToxic epidermal necrolysis or Stevens Johnson syndrome may occur from allopurinol MTB S2CK  ‐ p. 170 Don’t start uricosuric agents or allopurinol during acute attacks of gout. If the patient is already on allopurinol you can safely continue it. Calcium Pyrophosphate Deposition Disease  (Pseudogout)/Definition/Etiology • Calcium-containing salts depositing in articular cartilage • Most common risk – Hemochromatosis and hyperparathyroidism • CPDD can occur:• CPDD can occur: – Diabetes – Hypothyroidism – Wilson disease MTB S2CK  ‐ p. 170 Calcium Pyrophosphate Deposition Disease  (Pseudogout)/Presentation • CPDD differs from gout in that large joints such as the knee and wrist are affected, but not particularly the first MCP of the footMCP of the foot • It differs from DJD in that DIP and PIP aren’t affected MTB S2CK  ‐ p. 170 Calcium Pyrophosphate Deposition Disease  (Pseudogout)/Diagnostic Tests • Uric acid levels normal • X-ray: calcification of cartilaginous structures • Most accurate test is arthrocentesis, which reveals positively birefringent rhomboid-p y g shaped crystals • Synovial fluid: elevated level of WBCs 2,000 to 50,000/μL - nonspecific MTB S2CK  ‐ p. 170 Pseudogout Source Wikimedia Pseudogout Source: Boma O. Afiesimama 6 Calcium Pyrophosphate Deposition Disease  (Pseudogout)/Diagnostic Tests You cannot confirm a diagnosis of CPDD without aspiration of the joint. MTB S2CK  ‐ p. 170 Disease Characteristic  History Physical     Findings Synovial Fluid  Analysis DJD Older, slow,  worse with use DIP, PIP, hip,  and knees  50,000  neutrophils,  culture of fluid MTB S2CK  ‐ p. 171 Calcium Pyrophosphate Deposition Disease  (Pseudogout)/Treatment • Best initial therapy: NSAIDs • Severe disease not responsive to NSAIDs give intra-articular steroids (e g triamcinolone)(e.g., triamcinolone) • Colchicine helps prevent subsequent attacks as prophylaxis between attacks MTB S2CK  ‐ p. 171 Low Back Pain & Lumbar  Spinal Stenosis 7 Low Back Pain/Etiology • Low back pain is No. 1 complaint in US • DJD on X-ray or MRI of the spine is nearly universal in those > 50 years – totally nonspecific • Most frequently tested issue is who shouldn’t get an imaging study MTB S2CK  ‐ p. 171 Low Back Pain “What Is the Most Likely Diagnosis?” • If all diseases described in the following are excluded, patient has simple low back pain from “lumbosacral strain” (idiopathic)(idiopathic) • No imaging studies and no treatment beyond NSAIDs MTB S2CK  ‐ p. 171 Compression of the Spinal Cord • Malignancy or infection compressing spinal cord is a neurological emergency that needs urgent identification and treatment • Look for a history of cancer with suddenLook for a history of cancer with sudden onset of focal neurological deficits (e.g., sensory level) MTB S2CK  ‐ p. 171 Compression of the Spinal Cord • Compression at 10th thoracic vertebra leads to sensory loss below the umbilicus • Point tenderness at spine with percussion of vertebra is highlypercussion of vertebra is highly suggestive of cord compression • Hyperreflexia is found below level of compression MTB S2CK  ‐ p. 172 Compression of the Spinal Cord • Epidural abscess is most often from Staphylococcus aureus • Epidural abscess presents in same way as cord compression from cancer, but there’s high fever and markedlythere s high fever and markedly elevated ESR MTB S2CK  ‐ p. 172 Disk Herniation (Sciatica) • Herniations at L4/5 and L5/S1 level account for 95% of all disk herniations • The straight leg raise (SLR) test is pain going into the buttock and below the knee when the leg is raised > 60 degrees – Although only 50% of those with a positive SLR actually have a herniated disk; sensitivity is 90% – A negative SLR excludes herniation with 95% sensitivity MTB S2CK  ‐ p. 172 8 Nerve root Motor deficit Reflex  affected (lost) Sensory area  affected L4 L5 Dorsiflexion  of foot Dorsiflexion Knee jerk None Inner calf Inner Nerve Root Innervation MTB S2CK  ‐ p. 172 L5 S1 Dorsiflexion  of toe Eversion of  foot None  Ankle jerk Inner  forefoot Outer foot Low Back Pain/Diagnostic Tests • Imaging required for cord compression, epidural abscess, ankylosing spondylitis, and cauda equina syndrome • Best initial test for cancer with compression, infection, and fractures is plain X-ray • Most accurate test is MRI • CT scan is used as most accurate test if there’s a contraindication to MRI (e.g., pacemaker) • Intrathecal contrast must be given to increase accuracy (CT myelogram) MTB S2CK  ‐ p. 172 Low Back Pain/Diagnostic Tests • Imaging in disk herniation is controversial • We recommend you answer “no MRI” for just low back pain and MTB S2CK  ‐ p. 172‐173 a positive SLR alone • Neurological deficits = MRI Source: Nirav Thakur, MD. Classification of Back Pain Diagnosis  History to answer  “Most Likely Diagnosis Physical Findings Cord  Compression Epidural abscess History of cancer Fever high ESR Vertebral tenderness,  sensory level,  hyperreflexia  Same as cord MTB S2CK  ‐ p. 173 Epidural abscess Cauda equina Fever, high ESR Bowel and bladder  incontinence,  erectile dysfunction Same as cord  compression Bilateral leg weakness,  saddle area anesthesia Classification of Back Pain Diagnosis  History to answer  “Most Likely Diagnosis Physical Findings Ankylosing  spondylitis  Under age 40, pain  worsens with rest  and improves with  activity Decreased chest  mobility MTB S2CK  ‐ p. 173 Disk herniation Pain/numbness of  medial calf or foot Loss of knee and ankle  reflexes, positive  straight leg raise Low Back Pain/Treatment  Chemotherapy for Lymphoma Cord Compression Systemic Gl ti id MTB S2CK  ‐ p. 174 Radiation for Solid Tumors pGlucocorticoids 9 Low Back Pain/Treatment  MRSA Epidural Abscess Acute Neurologic Deficits Vancomycin Linezolid MTB S2CK  ‐ p. 174 MSSA p Systemic Glucocorticoids Oxacillin Nafcillin Cefazolin Low Back Pain/Treatment  • Beta-lactam antibiotics when organism is sensitive • Gentamicin = synergy with staph • Surgical drainage for larger collections Thi k f id l b lik d diti MTB S2CK  ‐ p. 174 • Think of epidural abscess like endocarditis • Use vancomycin as initial empiric therapy • Switch to oxacillin if it’s sensitive • Drain it if the infection is large enough to produce neurological deficits or it doesn’t respond to antibiotics alone Low Back Pain/Treatment  • Cauda equina syndrome: surgical decompression • Disk herniation (sciatica): NSAIDs with continuation of ordinary activities • Steroid injection into epidural space achieves id d d ti b fit f th ithrapid and dramatic benefit for those with sciatica • Surgery rarely needed MTB S2CK  ‐ p. 174 The most common wrong answer for sciatica is bed rest. Man with a history of prostate cancer comes to the emergency department with severe back pain and leg weakness. He has tenderness of the spine, hyperreflexia, and decreased sensation below his umbilicus. What is the most appropriate next step? a. Dexamethasone b. MRI c. X-ray Low specificity Save neurons before seeing them  d. Radiation e. Flutamide f. Ketoconazole g. Finasteride h. Leuprolide i. Biopsy j. Orchiectomy MTB S2CK  ‐ p. 174‐175 Best long-term treatment Dangerous with peripheral blockade Not fast enough to stop androgens Not fast enough to save neurons Not fast enough Not fast enough to stop androgens Only if cause unclear Low Back Pain/Treatment  • Most commonly tested point: no imaging studies in patients without focal neurological abnormalities or withneurological abnormalities or with simple lumbosacral strain MTB S2CK  ‐ p. 175 Lumbar Spinal Stenosis/Presentation • Look for a person > 60 with back pain while walking, radiating into buttocks and thighs bilaterally • Pain described as worse when walking downhill, and better when sitting, but the pedal pulses and ankle/brachial index are normal MTB S2CK  ‐ p. 175 Spinal stenosis can simulate peripheral arterial disease, but vascular studies are normal. 10 Lumbar Spinal Stenosis/Presentation • Unsteady gait and leg weakness when walking also occur • About ¼ have diminished lower extremity reflexes • Pain is less with activities in which• Pain is less with activities in which patient is leaning forward (e.g., cycling) MTB S2CK  ‐ p. 175 Lumbar Spinal Stenosis/Treatment • The only test is MRI • Weight loss and steroid injections into the lumbar epidural space improve 25% to 50% of cases • Surgical correction to dilate the spinal• Surgical correction to dilate the spinal canal is needed in 75% of patients MTB S2CK  ‐ p. 175 Fibromyalgia, Carpal Tunnel  Syndrome, & Dupuytren  ContractureContracture Fibromyalgia “What Is the Most Likely Diagnosis?” • Look for young woman with chronic musculoskeletal pain and tenderness with trigger points of focal tenderness at trapezius, medial fat pad of knee, and lateral epicondyle • Cause is unknown • Pain occurs at many sites (neck, shoulders, back, and hips) with: – Stiffness, numbness, and fatigue – Headaches – Sleep disorder MTB S2CK  ‐ p. 176 Fibromyalgia/Diagnostic Tests • No test to confirm fibromyalgia • Based on complex of symptoms, trigger points at predictable points • All lab tests are normal (e.g., ESR, C- reactive protein rheumatoid factor (RF)reactive protein, rheumatoid factor (RF), and CPK levels) MTB S2CK  ‐ p. 176 Fibromyalgia/Treatment • Best initial therapy is amitriptyline • Other treatments are milnacipran and pregabalin • Milnacipran is an inhibitor of serotonin and norepinephrine reuptake and is approved specifically for the management of fibromyalgia • Trigger point injections with local anesthetic are also sometimes used MTB S2CK  ‐ p. 176 Steroids are the wrong answer for fibromyalgia. 11 Carpal Tunnel Syndrome/Definition • Peripheral neuropathy from compression of median nerve as it passes under the flexor retinaculum • Pressure on nerve interferes with its sensory and motor functionsensory and motor function MTB S2CK  ‐ p. 176 Carpal Tunnel Syndrome/Etiology Acromegaly Median Nerve Pregnancy Amyloidosis Hypothyroidism MTB S2CK  ‐ p. 176 Diabetes Compression Rheumatoid Arthritis Carpal Tunnel Syndrome “What Is the Most Likely Diagnosis?” • Look for “pain in hand” affecting the palm, thumb, index finger, and radial half of ring finger, muscle atrophy of thenar eminence • Pain is worse at night and more frequent in those whose work involves prolonged use of the hands (e.g., typing) MTB S2CK  ‐ p. 177 Carpal Tunnel Syndrome/Diagnostic Tests • Tinel sign: reproduction of pain and tingling with tapping or percussion of the medianthe median nerve MTB S2CK  ‐ p. 177 IMC© 2010 DxR Development Group, Inc. All Rights Reserved. Carpal Tunnel Syndrome/Diagnostic Tests • Phalen sign: reproduction of symptoms with flexion of wrists to 90 degrees MTB S2CK  ‐ p. 177 IMC© 2010 DxR Development Group, Inc. All Rights Reserved. Carpal Tunnel Syndrome/Diagnostic Tests • Most accurate diagnostic tests are electromyography and nerve conduction testing MTB S2CK  ‐ p. 177 Sensory symptoms happen before motor symptoms. 12 Carpal Tunnel Syndrome/Treatment Best Initial • Wrist Splints • Immobilization to relieve pressure • NSAIDS Avoid Manual Activity St id Management MTB S2CK  ‐ p. 177 Steroid Injection is used if splints and NSAIDs don’t control Surgery Can be curative by mechanically decompressing the tunnel such as with cutting open the flexor retinaculum Dupuytren Contracture • Hyperplasia of palmar fascia leading to nodule formation and contracture of fourth and fifth fingers • Genetic predisposition and association with alcoholism and cirrhosis • Patients lose ability to extend fingers, which is more often cosmetic embarrassment than functional impairment • Triamcinolone injection • Surgical release when function is impaired MTB S2CK  ‐ p. 177 Dupuytren Contracture Commons.Wikimedia.org. used with permission Sports Medicine &  Osteoporosis Rotator Cuff Injury • Damage to rotator cuff of muscles, tendons, and bursae around shoulder leads to inability to flex or abduct the shoulder • It presents with pain in shoulder that’sIt presents with pain in shoulder that s worse at night when lying on affected shoulder • There can be severe tenderness at the insertion of the supraspinatus MTB S2CK  ‐ p. 177 Rotator Cuff Injury • MRI is the most accurate test • Treat with NSAIDs, rest, and physical therapyphysical therapy • Steroids • Surgery MTB S2CK  ‐ p. 177 Commons.Wikimedia.org. used with permission 13 Patellofemoral Syndrome • Cause of anterior knee pain secondary to trauma, imbalance of quadriceps strength, or meniscal tear • Pain in front of knee or underneath patella • Particularly bad when walking up or down stairsstairs • Worse just after starting to walk after having been seated for a prolonged period • It improves after walking MTB S2CK  ‐ p. 178 Patellofemoral Syndrome • Crepitus, joint locking, and instability • X-rays: normal • Most cases respond to physical therapy and strength training with cycling K b d ’t h l• Knee braces don’t help • There’s nothing to fix surgically MTB S2CK  ‐ p. 178 Plantar Fasciitis • Very severe pain in bottom of foot near calcaneus where fascia inserts • Pain worst in the morning and improves with walking a few steps • Point tenderness @ the fascia inserts at• Point tenderness @ the fascia inserts at the calcaneus MTB S2CK  ‐ p. 178 Plantar Fasciitis Commons.Wikimedia.org. used with permission Plantar Fasciitis • Treatment consists of stretching exercises, arch supports, and NSAIDs • Steroid injection is performed if these don’t solve problem • Surgical release of plantar fascia is rarely necessary MTB S2CK  ‐ p. 178 X-ray of the foot is not useful in plantar fasciitis. There is no correlation with the presence of heel spurs. Osteoporosis • Look for an older person, more often a woman, with vertebral fractures leading to loss of height or wrist fracture • Asymptomatic, fractures are found on routine screening with bone MTB S2CK  ‐ p. 198 routine screening with bone densitometry, which is recommended for all women > 65 Osteoporosis gives spontaneous fractures of weight-bearing bones. 14 Osteoporosis/Diagnostic Tests • Most accurate test is bone densitometry (DEXA) scanning • Osteopenia: bone density (T-score) is between 1 and 2.5 standard deviations below normal MTB S2CK  ‐ p. 198 below normal • Osteoporosis: T-score > 2.5 standard deviations < normal Osteoporosis/Treatment 1. Vitamin D and calcium are the best initial therapy 2. Bisphosphonates (alendronate, risendronate, ibandronate) 3 Estrogen replacement MTB S2CK  ‐ p. 198 3. Estrogen replacement 4. Raloxifene Osteoporosis/Treatment 1. Teriparatide is an analogue of PTH that stimulates new bone matrix formation 2. Used as a nasal spray, calcitonin decreases vertebral fractures risk MTB S2CK  ‐ p. 198 Bisphosphonates that have prolonged contact with the esophagus can cause esophagitis (pill esophagitis). Bisphosphonates are very rarely associated with osteonecrosis of the jaw. Osteoporosis/Treatment • When multiple treatment options are presented, choose vitamin D, calcium, and bisphosphonates. MTB S2CK  ‐ p. 198 Teriparatide has caused osteosarcoma in rats. It has also caused hypercalcemia. Rheumatoid Arthritis, Systemic  Lupus Erythematosus, &  Antiphospholipid Syndromep p p y Rheumatoid Arthritis/Definition/Etiology • RA is an autoimmune disorder predominantly of joints • More common in women MTB S2CK  ‐ p. 178 15 Rheumatoid Arthritis/Definition/Etiology • Chronic synovitis leads to overgrowth, or pannus formation, which damages all the structures surrounding the joint (bone, ligaments, tendons, and cartilage)g ) MTB S2CK  ‐ p. 178 Morning stiffness of multiple small, inflamed joints is key to diagnosis. Rheumatoid Arthritis/Presentation Morning Stiffness > 30 min Rheumatoid ArthritisRheumatoid PIP – Hands MCP – Hands Bilateral Symmetrical MTB S2CK  ‐ p. 178 Lung nodules and effusions Rheumatoid Nodules Episcleritis Vasculitis Rheumatoid Arthritis/Presentation • C1 and C2 laxity - subluxation • Baker cyst • Pericarditis and pleural disease • Carpal tunnel syndrome MTB S2CK  ‐ p. 179 DIP is spared in RA. DIP involvement happens in DJD. Rheumatoid Arthritis/Presentation • Boutonniere and swan neck are classic deformities of the hands MTB S2CK  ‐ p. 179 Source: Nirav Thakur, MD. Rheumatoid Arthritis © Richard Usatine, M.D. Used with permission. Rheumatoid Arthritis/Diagnostic Tests • Rheumatoid factor (RF) in 70% to 80% • RF is rather nonspecific • Anti-cyclic citrulinated peptide (anti- CCP) is > 80% sensitive and > 95% specificspecific MTB S2CK  ‐ p. 179 16 Rheumatoid Arthritis/Diagnostic Tests • Elevated ESR or C-reactive protein • Anemia: normocytic • Arthrocentesis on initial presentation excludes crystal disease or infection if diagnosis isn’t clear • Modest elevation in lymphocytes MTB S2CK  ‐ p. 179 Sicca syndrome: dry eyes, mouth, and other mucous membranes Rheumatoid Arthritis/Diagnostic Tests Felty syndrome: • RA • Splenomegaly • Neutropenia MTB S2CK  ‐ p. 180 Caplan syndrome: • RA • Pneumoconiosis • Lung nodules Rheumatoid Arthritis/Diagnostic Tests • The most important issue in RA is stopping the progression of the disease. Any patient with erosive disease or X-ray abnormalities needs at least methotrexate to slow disease progression. MTB S2CK  ‐ p. 180 The MCC of death in RA is coronary artery disease. Rheumatoid Arthritis/Treatment • Disease-Modifying Antirheumatic Drugs (DMARD) • Neither NSAIDs nor steroids stop RA from progressing • Any patient with erosive RA needs• Any patient with erosive RA needs DMARD as part of initial therapy MTB S2CK  ‐ p. 180 Patient with long-standing RA is to have coronary bypass surgery. Which is most important prior to surgery? a. Cervical spine X-ray b Rheumatoid factor  Already diagnosed to have RAb. Rheumatoid factor c. Extra dose of methotrexate d. ESR e. Pneumococcal vaccination MTB S2CK  ‐ p. 180 Already diagnosed to have RA Doesn’t change outcomes Nonspecific test Has nothing to do with surgery Rheumatoid Arthritis/Treatment “Erosive” disease means: • Joint space narrowing • Physical deformity of joints • X-ray abnormalities MTB S2CK  ‐ p. 180 y 17 Rheumatoid Arthritis/Treatment Methotrexate • Best initial DMARD • Adverse effects are: –Liver toxicity –Bone marrow suppression –Pulmonary toxicity MTB S2CK  ‐ p. 181 Rheumatoid Arthritis/Treatment Tumor Necrosis Factor (TNF) Inhibitors (infliximab, adalimumab, etanercept) • TNF inhibitors are first line as DMARDS • Toxicity of anti TNF drugs:• Toxicity of anti-TNF drugs: –Reactivation of TB –Infection MTB S2CK  ‐ p. 181 Rheumatoid Arthritis/Treatment Rituximab • RA as a DMARD by removing CD20+ lymphocytes from circulation • Excellent long-term • +/- methotrexate• +/- methotrexate MTB S2CK  ‐ p. 181 Rheumatoid Arthritis/Treatment Hydroxychloroquine • Rare as monotherapy as a DMARD • More often used in combination with methotrexate as a DMARD • Toxic to retina MTB S2CK  ‐ p. 181 Hydroxychloroquine leads to retinal toxicity. Do a dilated eye exam. Rheumatoid Arthritis/Treatment Symptomatic Control of RA • NSAIDs are the best initial therapy for the pain of RA • Steroids also work in a matter of hours to control the pain of RA secondary toto control the pain of RA secondary to inflammation • Steroids for 2 purposes –NSAIDS aren’t working –Bridge MTB S2CK  ‐ p. 181 Rheumatoid Arthritis/Treatment • Use TNF inhibitors as a DMARD with methotrexate after methotrexate fails • Adverse effects are mandatory for you to knowto know MTB S2CK  ‐ p. 181‐182 Steroids don’t prevent the progression of RA. 18 Adverse Effects of RA Medications Drug Adverse effect Anti‐TNF Hydroxychloroquine Sulfasalazine Reactivation of tuberculosis Ocular Rash, hemolysis MTB S2CK  ‐ p. 182 Rituximab Gold salts Methotrexate y Infection Nephrotic syndrome Liver, lung, marrow Juvenile Rheumatoid Arthritis or  Adult Still Disease Definition/Etiology • Juvenile rheumatoid arthritis (JRA) is very difficult to define and there’s no known etiologyknown etiology MTB S2CK  ‐ p. 182 Juvenile Rheumatoid Arthritis or  Adult Still Disease Presentation • The most important feature of JRA is the presence of high, spiking fever (often > 104°F) in a young person that(often > 104 F) in a young person that has no clearly identified etiology, but is associated with a rash MTB S2CK  ‐ p. 182 Juvenile Rheumatoid Arthritis or  Adult Still Disease/Presentation  Features of JRA rash: • Often only with fever spikes • “Salmon” colored • On chest and abdomen MTB S2CK  ‐ p. 182 Other features of JRA: • Splenomegaly • Pericardial effusion • Mild joint symptoms Juvenile Rheumatoid Arthritis or  Adult Still Disease Laboratory Abnormalities • No clear diagnostic test; anemia and leukocytosis often present • ANA is normal • Ferritin level markedly elevated• Ferritin level markedly elevated Treatment • Half of cases improve with aspirin or NSAIDs • If there’s no response then use steroids MTB S2CK  ‐ p. 183 Systemic Lupus Erythematosus Definition/Etiology • Autoimmune disorder • Inflammation diffusely through body MTB S2CK  ‐ p. 183 19 Systemic Lupus Erythematosus Presentation • Diagnosis of SLE is based on 4 of 11 known manifestations of disease • Four skin-related manifestations: 1. Malar rash 2. Discoid rash 3. Photosensitivity 4. Oral ulcers MTB S2CK  ‐ p. 183 Alopecia is common in SLE, but isn’t one of the “official” diagnostic criteria. Systemic Lupus Erythematosus © Richard Usatine, M.D. Used with permission. Systemic Lupus Erythematosus Presentation • Joint: arthritis is present in 90% • X-ray is normal • Serositis: inflammation of pleura and i di h t ipericardium – chest pain MTB S2CK  ‐ p. 183 Systemic Lupus Erythematosus Presentation • Renal: any degree of abnormality can occur from mild proteinuria to end-stage renal disease requiring dialysis – Most common glomerulonephritis is g p membranous – Red cell casts and hematuria occur • Neurologic: symptoms include psychosis, seizures, or stroke from vasculitis MTB S2CK  ‐ p. 183 Systemic Lupus Erythematosus Pneumonia, alveolar hemorrhage, and restrictive lung disease happen in SLE, but aren’t criteria for diagnosis of the disease. MTB S2CK  ‐ p. 183 g Systemic Lupus Erythematosus Ocular findings aren’t part of formal diagnostic criteria: • Photophobia • Retinal lesions (cotton wool MTB S2CK  ‐ p. 184 ( spots) • Blindness 20 Systemic Lupus Erythematosus Presentation • Hematologic: hemolytic anemia is part of diagnostic criteria, but anemia of chronic disease is more commonly foundfound • Lymphopenia, leukopenia, and thrombocytopenia are also seen MTB S2CK  ‐ p. 184 Systemic Lupus Erythematosus Presentation • Immunologic (laboratory) abnormalities - criteria include positive ANA, or any one of the following: – Anti-double-stranded DNA– Anti-double-stranded DNA – Anti-Sm – False positive test for syphilis – Positive LE cell preparation MTB S2CK  ‐ p. 184 Systemic Lupus Erythematosus Additional findings: • Mesenteric vasculitis • Raynaud phenomenon MTB S2CK  ‐ p. 184 • Antiphospholipid syndromes Systemic Lupus Erythematosus Diagnostic tests • ANA: found in 95% to 99% of cases • Anti-double-stranded DNA (60%) and anti-Sm (30%): Fo nd onl in SLE– Found only in SLE – Extremely specific for SLE MTB S2CK  ‐ p. 184 Systemic Lupus Erythematosus Diagnostic tests • Decreased complement levels: – Correlate with disease activity – Drop further with acute disease exacerbations • Anti-SSA and anti-SSB: found in 10% to 20% of cases – Add little to diagnosis – Tests most often found in Sjögren syndrome (65% of cases) MTB S2CK  ‐ p. 184 Don’t treat asymptomatic ANA 34-year-old woman with history of SLE is admitted with pneumonia and confusion. As you’re wrestling with the decision over a bolus of high-dose steroids in a person with an infection, you need to determine if this is a flare of lupus or simply an infection with sepsis causing confusion. Which of the following will help you the most?Which of the following will help you the most? a. Rise in anti-Sm b. Rise in ANA c. Decrease in complement and rise in anti-DS DNA d. MRI of the brain e. Response to steroids MTB S2CK  ‐ p. 184‐185  Not diagnostic MRI doesn’t diagnose regardless Level doesn’t change in acute disease Level doesn’t change in acute disease 21 Systemic Lupus Erythematosus Treatment • Acute lupus flare treated with high-dose boluses of steroids • Hydroxychloroquine can control mildly chronic disease Lupus nephritis may need steroids either• Lupus nephritis may need steroids either alone or in combination with cyclophosphamide or mycophenolate • Only way to determine the severity of lupus nephritis is kidney biopsy • Belimumab decreases symptoms MTB S2CK  ‐ p. 185 Systemic Lupus Erythematosus Treatment • Urinalysis is insufficient to determine severity of lupus nephritis • Biopsy is the only way to diagnose simple glomerulosclerosis or scarring of the kidney, which will not respond to therapy MTB S2CK  ‐ p. 185 Young patients most commonly die of infection. In older patients, accelerated atherosclerosis makes MI the MCC of death. Antiphospholipid Syndrome/Definition • Idiopathic disorder with IgG or IgM antibodies made against negatively charged phospholipids • The 2 main types are: – Lupus anticoagulant– Lupus anticoagulant – Anticardiolipin antibodies MTB S2CK  ‐ p. 185 Antiphospholipid Syndrome Presentation/Diagnostic Tests • Thromboses of both arteries and veins as well as recurrent spontaneous abortions • Elevation of aPTT with a normal prothrombin time (PT) and normal INR MTB S2CK  ‐ p. 185 APL = clotting + elevated aPTT and normal PT Antiphospholipid Syndrome Presentation/Diagnostic Tests • False positive VDRL or RPR with a normal FTA • Anticardiolipin antibodies - spontaneous abortionabortion • Lupus anticoagulant - elevated aPTT • Best initial test is mixing study MTB S2CK  ‐ p. 185‐186 Antiphospholipid Syndrome Diagnostic Tests • If the elevation in aPTT is from a clotting factor deficiency then aPTT will come down to normal • If the APL syndrome antibody is present in plasma then aPTT remains elevated M t ifi t t f l ti l t i• Most specific test for lupus anticoagulant is Russell viper venom test (RVVT) • RVVT is prolonged with APL antibodies and doesn’t correct on mixing with normal plasma MTB S2CK  ‐ p. 186 22 Antiphospholipid Syndrome/Treatment • Thromboses (DVT or PE) treated with heparin and warfarin as you would any other form of thrombosis with an INR of 2 to 3 • Lifelong vs. 6 months – primary occurrence • Recurrent thrombotic episodes are treated lifelong MTB S2CK  ‐ p. 186 Antiphospholipid Syndrome/Treatment • USMLE S2 CK questions have to be unequivocally clear. If an area is controversial, USMLE will avoid it and ask only what is clear The exam will notask only what is clear. The exam will not trick you. MTB S2CK  ‐ p. 186 Antiphospholipid Syndrome/Treatment • Warfarin or steroids are wrong answers for preventing spontaneous abortion. Steroids aren’t effective. MTB S2CK  ‐ p. 186 Warfarin is contraindicated in pregnancy secondary to teratogenicity. Scleroderma, Polymyositis, &  Dermatomyositis Scleroderma (Systemic Sclerosis) Limited scleroderma is also known as CREST syndrome: • Calcinosis • Raynaud E h l d tilit• Esophageal dysmotility • Sclerodactyly • Telangiectasia MTB S2CK  ‐ p. 186 Scleroderma (Systemic Sclerosis) “What is the most likely diagnosis?” • Look for a young (20s to 40s) woman (3 times more likely than men) with fibrosis of the skin and internal organs (e.g., lung kidney and GI tract)lung, kidney, and GI tract) MTB S2CK  ‐ p. 187 23 Scleroderma/Presentation • Raynaud syndrome: increased vascular reactivity of fingers beginning with pain and pallor (white) or cyanosis (blue) followed by reactive hyperemia (red) • Skin manifestations: fibrosis of hands, face, k d t iti t l i t i dneck, and extremities; telangiectasia and abnormalities of pigmentation occur MTB S2CK  ‐ p. 187 Raynaud Syndrome Scleroderma Scleroderma (Systemic Sclerosis) MTB S2CK  ‐ p. 187 Scleroderma/Presentation • GI: esophageal dysmotility with GERD, large-mouthed diverticuli of small and large bowel • Renal: sudden hypertensive crisis • Lung: fibrosis leading to restrictive lung MTB S2CK  ‐ p. 187 disease and pulmonary hypertension • Cardiac: myocardial fibrosis, pericarditis, and heart block; lung disease gives right ventricular hypertrophy Scleroderma/Diagnostic Tests • ANA: positive in 85% to 90%, but nonspecific • ESR: usually normal • SCL-70: most specific test (anti- topoisomerase) MTB S2CK  ‐ p. 187 • Anticentromere: present in half of those with CREST syndrome Anticentromere antibodies are extremely specific for CREST syndrome. 24 Scleroderma/Treatment • Penicillamine is ineffective • Renal crisis: ACE inhibitors • Esophageal dysmotility: PPIs for GERD • Raynaud: calcium-channel blockers • Pulmonary fibrosis: cyclophosphamide MTB S2CK  ‐ p. 187 Pulmonary fibrosis: cyclophosphamide improves dyspnea and PFTs • Pulmonary hypertension is treated like primary pulmonary hypertension with bosentan or ambrisentan (endothelin antagonist) or Sildenafil Polymyositis and Dermatomyositis Presentation • Proximal muscle weakness • They don’t affect facial or ocular muscles as occurs in myasthenia gravis • Dysphagia MTB S2CK  ‐ p. 188 • Dysphagia Polymyositis and Dermatomyositis Presentation Dermatomyositis presents with: • Malar involvement • Shawl sign: erythema of face, neck, shoulders, upper chest, and back MTB S2CK  ‐ p. 188 , pp , • Heliotrope rash: edema and purplish discoloration of eyelids • Gottron papules: scaly patches over the back of hands, particularly PIP and MCP joints Polymyositis and Dermatomyositis Commons.Wikimedia.org. used with permission Polymyositis and Dermatomyositis Commons.Wikimedia.org. used with permission Polymyositis and Dermatomyositis Commons.Wikimedia.org. used with permission 25 Polymyositis and Dermatomyositis/ Presentation Dermatomyositis is associated with cancer in 25% of cases. Common sites are: • Ovary MTB S2CK  ‐ p. 188 y • Lung • GI • Lymphoma Polymyositis and Dermatomyositis Diagnostic Tests • Best initial test is CPK and aldolase • Most accurate test is muscle biopsy • ANA is frequently positive MTB S2CK  ‐ p. 188 • MRI • Electromyography Polymyositis and Dermatomyositis Treatment • Steroids are usually sufficient • When patient is unresponsive or intolerant of steroids, use: – Methotrexate MTB S2CK  ‐ p. 188‐189 – Azathioprine – IVIG – Mycophenolate • Hydroxychloroquine helps skin lesions Sjögren Syndrome,  Vasculitis, & Seronegative  SpondyloarthropathiesSpondyloarthropathies Sjögren Syndrome/Definition/Etiology  • Idiopathic autoimmune disorder secondary to antibodies predominantly against lacrimal and salivary glands • 90% of those affected are women • Sjögren syndrome is associated with: MTB S2CK  ‐ p. 189 – RA – SLE – Primary biliary cirrhosis – Polymyositis – Hashimoto thyroiditis Sjögren Syndrome/Presentation  • Sjögren presents with dryness of mouth and eyes • Keratoconjunctivitis sicca • Need to constantly drink water D h i MTB S2CK  ‐ p. 189 • Dysphagia • Dental caries 26 Sjögren Syndrome/Presentation  • Less common manifestations are: – Vasculitis – Lung disease – Pancreatitis – Renal tubular acidosis (20%) Loss of vaginal secretions leads to dyspareunia. MTB S2CK  ‐ p. 189 Renal tubular acidosis (20%) • Lymphoma is the most “dangerous” complication of Sjögren Sjögren Syndrome/Diagnostic Tests  • Best initial test is called a Schirmer test • Most accurate test is a lip or parotid gland biopsy • Reveal lymphoid infiltration in salivary glands MTB S2CK  ‐ p. 189‐190 glands Sjögren Syndrome/Diagnostic Tests  • Best initial test on blood: SS-A and SS-B • These are also called “Ro” and “La” and each are present in about 65% of patients MTB S2CK  ‐ p. 190 patients – SLE is associated with SS-A and SS-B in 10% to 20% of cases – Other abnormalities that are present, but are nonspecific: ANA, RF, anemia, leukopenia, and eosinophilia Sjögren Syndrome/Treatment  • Best initial therapy is to water the mouth • Use frequent sips of water, sugar-free gum, and fluoride treatments • Artificial tears to avoid corneal ulcers • Pilocarpine and cevimeline increase t l h li th i ti l t t d MTB S2CK  ‐ p. 190 acetylcholine, the main stimulant to produce saliva • Cevimeline increases rate of saliva production • No cure • Evaluate for lymphoma Vasculitis • Etiology unknown • Symptoms develop over weeks to months • All vasculitides give: Fe er MTB S2CK  ‐ p. 190 – Fever – Malaise/fatigue – Weight loss – Arthralgia/myalgia Polyarteritis Nodosa/Definition • Polyarteritis nodosa (PAN) is a disease of small- and medium-sized arteries leading to a diffuse vasculitis that inexplicably spares the lungs • Chronic hepatitis B and C are MTB S2CK  ‐ p. 190 Chronic hepatitis B and C are associated with PAN 27 Polyarteritis Nodosa/Presentation Common Features of PAN • Renal: glomerulonephritis without a biopsy can’t be diagnosed – UA isn’t enough to confirm it’s PAN • Neurological: any large peripheral MTB S2CK  ‐ p. 190‐191 • Neurological: any large peripheral nerve can be involved – Peroneal neuropathy leading to foot drop • Look for a stroke in a young person Polyarteritis Nodosa/Presentation • Gastrointestinal: abdominal pain is worsened by eating from vasculitis of mesenteric vessels – Bleeding also occurs – Nausea and vomiting are common MTB S2CK  ‐ p. 191 Nausea and vomiting are common • Skin: lower extremity ulcers are most common; livedo reticularis, purpura, nodules, and rarely gangrene occur Lung is spared in PAN Polyarteritis Nodosa/Presentation Mononeuritis Multiplex • Mononeuritis multiplex is multiple peripheral neuropathies of nerves large enough to have a name MTB S2CK  ‐ p. 191 Polyarteritis Nodosa/Diagnostic Tests • Most accurate test is a biopsy of a symptomatic site • Angiography of renal, mesenteric, or hepatic artery shows abnormal dilation or “beading.” MTB S2CK  ‐ p. 191 • P-ANCA is present in < 20% Test all PAN patients for hepatitis B and C. Polyarteritis Nodosa/Treatment • Prednisone and cyclophosphamide • Treat hepatitis when found MTB S2CK  ‐ p. 191 Polymyalgia Rheumatica • Polymyalgia rheumatica (PMR) occurs in those over age 50 with: – Pain and stiffness in shoulder and pelvic girdle muscles – Difficulty combing hair and rising from chair Elevated ESR MTB S2CK  ‐ p. 191 – Elevated ESR – Normochromic, normocytic anemia • No Lab Findings • CPK and aldolase are normal • Steroids even at low doses – great response 28 Giant Cell (Temporal) Arteritis The difference is the presence of: • Visual symptoms • Jaw claudication (pain in jaw when chewing) • Scalp tenderness MTB S2CK  ‐ p. 191‐192 • Scalp tenderness • Headache • Symptoms in other arteries such as decreased arm pulses, bruits near the clavicles, or aortic regurgitation Giant Cell (Temporal) Arteritis • ESR and C-reactive protein are elevated • Most accurate test is a biopsy of affected artery (e.g., temporal artery) • Treat with prednisone • Starting high-dose prednisone quickly is MTB S2CK  ‐ p. 192 • Starting high-dose prednisone quickly is more important than waiting for biopsy Blindness is irreversible. Wegener Granulomatosis • Presents with: – Sinusitis – Otitis media – Mastoiditis – Oral and gingival involvement MTB S2CK  ‐ p. 192 • Wegener is also associated with skin, joint, and eye lesions • Look for combination of upper and lower respiratory tract findings in association with renal insufficiency Wegener Granulomatosis/Diagnostic Tests • Best initial test is antineutrophil cytoplasmic antibody (ANCA) • Most accurate test is a biopsy • Cytoplasmic antibodies are also called “C- ANCA.” MTB S2CK  ‐ p. 192 – C-ANCA = anti-proteinase-3 antibodies – P-ANCA = anti-myeloperoxidase antibodies Wegener: C-ANCA Churg-Strauss and microscopic polyangiitis: P-ANCA Wegener Granulomatosis/Diagnostic Tests When asked about the “best test” for Wegener, lung biopsy is better than renal biopsy with sinus biopsy being the least accurate MTB S2CK  ‐ p. 192 accurate When all 3 are in the choices choose lung biopsy Wegener Granulomatosis/Treatment • Treat with prednisone and cyclophosphamide The clue to answering the “most likely diagnosis” question is unresolving MTB S2CK  ‐ p. 192 diagnosis question is unresolving pneumonia not better with antibiotics. You will not first think of Wegener when presented with the case. 29 Churg‐Strauss Syndrome • Pulmonary-renal syndrome, Churg- Strauss also has: –Asthma –Eosinophilia Bi i th t t t t MTB S2CK  ‐ p. 193 • Biopsy is the most accurate test • Treat with prednisone and cyclophosphamide Henoch‐Schönlein Purpura • Vasculitis more frequently seen in children, Henoch-Schönlein purpura (HSP) is characterized by involvement of: – GI tract: pain, bleeding MTB S2CK  ‐ p. 193 p , g – Skin: purpura – Joint: arthralgia – Renal: hematuria Henoch‐Schönlein Purpura • HSP is most often a clinical diagnosis; however, biopsy is the most accurate test Serum IgA levels are the Th MTB S2CK  ‐ p. 193 wrong answer. They are unreliable when testing for Henoch-Schönlein purpura. Henoch‐Schönlein Purpura When the case describes leukocytoclastic vasculitis on biopsy, the answer is Henoch-Schönlein purpura. MTB S2CK  ‐ p. 193 • Leukoplastic reactions are painless, palpable purpura of buttocks and legs Source: Shreya Patel and Nishith Patel Henoch‐Schönlein Purpura/Treatment • Most cases resolve spontaneously • Steroids if there are severe extrarenal mainfestations associated with renal failure MTB S2CK  ‐ p. 193 Cryoglobulinemia • Most commonly associated with chronic hepatitis C • +/- endocarditis and/or Sjögren syndrome • Don’t confuse cryoglobulins with cold agglutinins MTB S2CK  ‐ p. 194 agglutinins – Both are IgM antibodies – Neither respond to steroids 30 Differences between Cryoglobulins and Cold Agglutinins Cryoglobulins Cold agglutinin Associated with Manifestations Hepatitis C Joint pain Glomerulonephritis EBV, Mycoplasma,  Lymphoma Hemolysis MTB S2CK  ‐ p. 194 Treatment Glomerulonephritis Purpuric skin lesions Neuropathy Interferon, Ribavirin, and  boceprevir (or  telaprevir) Stay warm Rituximab,  cyclophosphamide,  cyclosporine Cryoglobulinemia • Lab tests show a positive rheumatoid factor and cold precipitable immune complexes • Steroids NOT effective • Treat the underlying cause, especially hepatitis C, with interferon and ribavirin MTB S2CK  ‐ p. 194 • Despite the rarity of the condition, the USMLE loves cryoglobulinemia questions. SLE decreased C3 or 3 letters (SLE) = C3 Hep C decreased C4 or 4 letters (Hep C) = C4 . Behçet Syndrome • The most common Behçet questions are: –What is the most likely diagnosis? What is “pathergy”? MTB S2CK  ‐ p. 194 –What is pathergy ? Pathergy: sterile skin pustules from minor trauma (e.g., needle stick) Behçet Syndrome • Asian or Middle Eastern person with painful oral and genital ulcers +/- erythema • Also with: –Ocular lesions leading to uveitis and MTB S2CK  ‐ p. 194 Ocular lesions leading to uveitis and blindness –Arthritis –CNS lesions mimicking multiple sclerosis Behçet Syndrome/Treatment • Corticosteroids • To wean patients off of steroids, use: –Azathioprine –Cyclophosphamide C l hi i MTB S2CK  ‐ p. 195 –Colchicine –Thalidomide Seronegative Spondyloarthropathies The 3 types of seronegative spondyloarthropathies are: • Ankylosing spondylitis • Psoriatic arthritis MTB S2CK  ‐ p. 195 • Reactive arthritis (Reiter syndrome) 31 Seronegative Spondyloarthropathies Men < 40 years: • Involvement of spine and large joints • Negative rheumatoid factor (hence the name seronegative) • Enthesopathy (inflammation where MTB S2CK  ‐ p. 195 • Enthesopathy (inflammation where tendons and ligaments attach to bones) • Uveitis • HLA-B27 Seronegative Spondyloarthropathies • Corticosteroids aren’t a good treatment for seronegative spondyloarthropathy D it th i ti ith HLA B27 MTB S2CK  ‐ p. 195 • Despite the association with HLA-B27, this is never the “best initial” or “most accurate” test for seronegative spondyloarthropathies. Ankylosing Spondylitis/Diagnosis • Young man with low backache and stiffness of his back has pain that radiates to buttocks with flattening of the normal lumbar curvature and decreased chest expansion E t ll th i ill t d i MTB S2CK  ‐ p. 195 • Eventually the spine will not expand in any direction • Enthesopathy occurs at the Achilles tendon Look for back pain worsened by rest and relieved by activity Ankylosing Spondylitis/Diagnosis Other Findings of Ankylosing Spondylitis • Transient peripheral arthritis of knees, hips, and shoulders (50%) • Cardiac: atrioventricular block in 3% MTB S2CK  ‐ p. 195 • Cardiac: atrioventricular block in 3% to 5%; aortic insufficiency • Uveitis “Bamboo spine” is a late finding with fusion of vertebral joints. Ankylosing Spondylitis/Diagnostic Tests MTB S2CK  ‐ p. 196 Ankylosing Spondylitis/Diagnostic Tests • Best initial test is an X-ray of sacroiliac (SI) joint • Most accurate test is an MRI • MRI detects abnormalities years before the X ray becomes abnormal MTB S2CK  ‐ p. 196 the X-ray becomes abnormal • ESR is elevated in 85% 32 Ankylosing Spondylitis/Diagnostic Tests MTB S2CK  ‐ p. 196 Source: Conrad Fischer, MD. Ankylosing Spondylitis • HLA B27 is not a confirmatory diagnostic test since 8% of general population is positive Treatment • Exercise program and NSAIDs are best MTB S2CK  ‐ p. 196‐197 p g initial treatment • If NSAIDs are insufficient, use anti-TNF drugs (e.g., etanercept, adalimumab, or infliximab) Psoriatic Arthritis • Psoriatic arthritis 80% will have preceding psoriasis • Besides SI joint involvement, characteristic findings are: Sausage digits from enthesopathy MTB S2CK  ‐ p. 197 –Sausage digits from enthesopathy –Nail pitting Psoriatic Arthritis MTB S2CK  ‐ p. 197 Psoriatic Arthritis/Diagnostic Tests • ESR is elevated – nonspecific • Best initial test is an X-ray of the joint showing a “pencil in a cup” deformity MTB S2CK  ‐ p. 197 Psoriatic Arthritis/Treatment • NSAIDs are best initial therapy • Methotrexate used when question describes severe disease or no response to NSAIDs • Anti TNF agents are the answer when MTB S2CK  ‐ p. 197 • Anti-TNF agents are the answer when methotrexate doesn’t control disease • Steroids are a wrong choice 33 Reactive Arthritis (Reiter Syndrome) Reactive arthritis occurs secondary to: • Inflammatory bowel disease (equal sex incidence) • Sexually transmitted infection (far greater in men) MTB S2CK  ‐ p. 197 greater in men) • GI infection (Yersinia, Salmonella, Campylobacter) Reactive Arthritis/Diagnosis • Look for triad of: – Joint pain – Ocular findings (uveitis, conjunctivitis) G it l b liti ( th iti MTB S2CK  ‐ p. 198 – Genital abnormalities (urethritis, balanitis) Keratoderma blennorhagicum is a skin lesion unique to reactive arthritis that looks like pustular psoriasis. Reactive Arthritis/Diagnosis Source: commons.wikimedia.org. Used with permission Reactive Arthritis/Diagnostic Tests/Treatment • No specific test for reactive arthritis • Rule out septic joint • Treat underlying cause/use NSAIDs • Sulfasalazine > NSAIDS MTB S2CK  ‐ p. 198 Antibiotics don’t reverse reactive arthritis once joint pain has started. Septic Arthritis, Gonococcal  Arthritis, & Osteomyelitis   Septic Arthritis Definition • Septic arthritis is an infection of joint space Etiology • Septic arthritis is relatively rare in an undamaged joint MTB S2CK  ‐ p. 199  undamaged joint • Risk of infection is directly proportional to degree of joint damage 34 Septic Arthritis Etiology (cont’d) • Osteoarthritis (DJD) provides slight risk • RA has greater risk • Greatest risk is with prosthetic joint Bacteremia can spread into joint space MTB S2CK  ‐ p. 199  • Bacteremia can spread into joint space, which is why endocarditis and injection drug use causes septic arthritis Etiology of Septic Arthritis Etiology Frequency Staphylococcus Streptococcus 40% 30% MTB S2CK  ‐ p. 199  Gram‐negative  rods 20% Septic Arthritis/Presentation • Joint is warm, red, and immobile often with palpable effusion • Chills and fever happen because of bacteremia MTB S2CK  ‐ p. 199 Septic Arthritis/Diagnostic Tests • Best initial and most accurate test is aspiration of the joint with a needle (arthrocentesis); X-ray, CT, and MRI aren’t useful and are the wrong answers • Joint fluid shows: MTB S2CK  ‐ p. 199 – Leukocytosis: more than 50,000 to 100,000 cells, predominantly neutrophils – Gram stain: positive (50%) Gram-negative bacilli; (75%) with Staphylococcus – Synovial fluid culture: 70% to 90% sensitive – Blood cultures: 50% sensitive Septic Arthritis Treatment • Ceftriaxone and vancomycin are best initial empiric therapy MTB S2CK  ‐ p. 199 Other Options for Treatment of Septic Arthritis Gram‐negative  bacilli  Gram‐positive cocci  (sensitive) Gram‐positive  cocci (resistant) Quinolones  Aztreonam Oxacillin  Cefazolin Linezolid  Daptomycin  MTB S2CK  ‐ p. 200  Cefotaxime Piperacillin Aminoglycosides Piperacillin with  Tazobactam Ceftaraline Tigecycline 35 Septic Arthritis/Treatment • Adjust antibiotics according to culture results. If Staphylococcus is sensitive, MTB S2CK  ‐ p. 200 p y , vancomycin is associated with a worse outcome than betalactam antibiotic (e.g., oxacillin or cefazolin). Switch drugs if organism is sensitive. Septic Arthritis Prosthetic Joint Infection • Infected prosthetic joint gives a warm, red, immobile, and tender joint • Must do imaging MTB S2CK  ‐ p. 200  Septic Arthritis Prosthetic Joint Infection (cont’d) • MRI difficult to perform with prosthetic joints because they are made of metal • If there is lucency around implantation of the joint on radiologic imaging or if MTB S2CK  ‐ p. 200 of the joint on radiologic imaging or if joint is physically loose, infection is likely present at implantation site Septic Arthritis Treatment of Infected Prosthetic Joint • Remove joint, treat with antibiotics for 6 to 8 weeks, and then replace joint The most common MTB S2CK  ‐ p. 200 organism for recently placed artificial joints is Staphylococcus epidermidis. Gonococcal Arthritis (Gonorrhea) • The difference in presentation from septic arthritis is: – Polyarticular involvement – Tenosynovitis (inflammation of tendon sheaths, making finger movement painful) MTB S2CK  ‐ p. 200  – Petechial rash Gonococcal arthritis is more frequent during menses. Gonococcal Arthritis/Diagnostic Tests • Detecting gonorrhea is much more difficult than detecting Staphylococcus, Streptococcus, and Gram-negative bacilli of septic arthritis MTB S2CK  ‐ p. 200 36 Synovial Fluid Analysis for Infectious Arthritis Test sensitivity Septic arthritis Gonococcal arthritis Leukocytosis Gram stain C l > 50,000‐100,000 cells/μL 50‐70% sensitive 90% i i 30,000‐50,000 cells/μL 25% sensitive 50% i i MTB S2CK  ‐ p. 201  Culture  Blood cultures  90% sensitive 50% sensitive 37 Osteomyelitis/Diagnostic Tests • When is “culturing the drainage” the answer? – Never. You cannot reliably distinguish superficial colonization from whatever organism is inside the bone causing the MTB S2CK  ‐ p. 202 bone infection. Bone scan is the answer only if you want to get an MRI and it’s contraindicated (pacemaker). Osteomyelitis/Treatment • Osteomyelitis takes weeks to progress • Must biopsy • MSSA –Oxacillin, cefazolin, nafcillin, or ceftriaxone MTB S2CK  ‐ p. 202 ceftriaxone • MRSA –Vancomycin or linezolid Osteomyelitis/Treatment • Gram-negative bacilli such as E. coli are treated with fluoroquinolones (e.g., ciprofloxacin) – It’s essential to confirm the sensitivity of the organism prior to MTB S2CK  ‐ p. 202 treating with ciprofloxacin Ciprofloxacin is the only oral therapy for osteomyelitis, but should be used only if the organism is confirmed as a sensitive Gram-negative bacillus. Osteomyelitis/Treatment Toxicity of Quinolones • Fluoroquinolones can cause Achilles tendon rupture –They are also contraindicated in pregnancy and children because they MTB S2CK  ‐ p. 202 pregnancy and children because they interfere with bone growth 1 Surgery Matthew Kinney, MD Orthopedic Resident University of California San Diego Preoperative Evaluation,  Postoperative Evaluation, &  Vascular SurgeryVascular Surgery Preoperative Evaluation Cardiovascular Pulmonaryy Renal Preoperative Evaluation Objective: Identify factors that increase risk of complications in perioperative period • Age • Cardiac history – #1 predictor of perioperative complications • Diabetes status – “Risk equivalent” to Coronary disease • History of… – Pulmonary disease – Renal disease – Stroke MTB S2CK  ‐ p. 379 Preoperative Evaluation/Cardiac  Must obtain detailed cardiac history Look for indicators of previous MI or CHF • Recent MI – Defer surgery for 6 months – Follow-up stress test to ensure adequate perfusion • Evidence of CHF (JVD, edema) – Patients with EF < 35% at increased risk – ACE-Is, B-blockers, spironolactone must be optimized – Proven to decrease overall mortality!!! MTB S2CK  ‐ p. 379 Preoperative Evaluation/Cardiac Management • If age < 35 and no history of cardiac disease – EKG • If history of cardiac disease (MI, CHF) – EKG Stress testing– Stress testing • Ensure appropriate cardiac perfusion – Echocardiography • Monitor EF • Evaluate structural damage MTB S2CK  ‐ p. 380 2 71-year old man undergoing femoro-popliteal bypass for severe claudication of left leg which causes unbearable pain with exercise. Past medical/surgical history is significant for remote appendectomy and insulin-dependent type 2 DM. What preoperative testing is recommended?What preoperative testing is recommended? a.Basic Metabolic Panel (BMP) only b.BMP + EKG c.BMP + EKG + PFTs d.BMP + EKG + Exercise Stress Test e.BMP + EKG + Thallium Stress Test High cardiac risk Must get stress test/ECHO Cannot exercise Preoperative Evaluation/Pulmonary • Must evaluate for history of lung disease (including smoking) • PFTs required for all patients with known lung disease – Vital capacity - most important predictor of perioperative complicationsperioperative complications MTB S2CK  ‐ p. 380 Preoperative Evaluation/Pulmonary Preoperative Evaluation/Pulmonary • Must evaluate for history of lung disease (including smoking) • PFTs required for all patients with known lung disease – Vital capacity - most important predictor of perioperative complications • Smokers – PFTs – Smoking cessation for 6-8 weeks preoperatively • Nicotine patch acceptable MTB S2CK  ‐ p. 380 Preoperative Evaluation/Renal  • Renal disease increases surgical risk – Intravascular fluid losses occur during surgery • Results in hypoperfusion of kidneys – Physiologic response to decreased intravascular volume is activation of Renin-Angiotensin system • Constricts renal vasculature • Renal hypoperfusion correlates with increased mortality • Management – Aggressive IV hydration beginning 24 hours pre-op – Dialysis patients must be dialyzed 24 hours pre-op MTB S2CK  ‐ p. 380 Postoperative Evaluation Fever Assessment Complications 3 Post‐Operative Fever POD Atelectasis #1 Pneumonia DVT Thrombophlebitis (IV site infection) Drug Reaction Deep Abscess CXR -Sputum Culture (if pneumonia suspected) Doppler US D/C likely medication CT Scan Anti-coagulation •HeparinWarfarin Drainage 1-2 3-5 5-6 7 8-15 WIND WATER WALKING WOUND WEIRD MTB S2CK  ‐ p. 400 UTI Incision-site Infection Cellulitis Urinalysis •Nitrite “+” •Leukocyte Esterase “+” Physical Exam •Erythema •Pus •Swelling -Incentive spirometry -Antibiotics •Vanc. + Pip/Tazo Antibiotics p •Replace IVs •Abscess Incision/Drainage •Antibiotics of Abscess Post‐Op Complications/Confusion Confused Patient Evidence of Hypoxemia • Abnormal ABG Obtain ABG, CXR, CBC Culture Likely SourcesChanges on CXR? Evidence of Infection • Abnormal CBC MTB S2CK  ‐ p. 401 Treat with empiric Antibiotics • Blood (Bacteremia) • Urine (UTI)Yes No Atelectasis vs. Pneumonia • Incentive spirometry • Antibiotics Consider PE • Spiral CT Adult Respiratory Distress Syndrome Etiology • Endothelial damage allows fluid to fill alveoli – Prevents O2/CO2 exchange, acts as shunt Signs/Symptoms • ↑HR, ↑RR Labored breathing (accessory muscle use) MTB S2CK  ‐ p. 401 – Labored breathing (accessory muscle use) – Fever may be present Diagnosis • ABG: ↓pO2, ↑pCO2 • CXR: Bilateral pulmonary infiltrates Adult Respiratory Distress Syndrome © MS-4 USU Teaching File, Uniformed Services University Adult Respiratory Distress Syndrome Treatment • Mechanical ventilation –Maximize Positive End-Expiratory Pressure (PEEP) MTB S2CK  ‐ p. 401 Pulmonary Embolism Etiology • Passage of a venous blood clot to lungs – Origin: Deep leg vein > 90% • Clot lodges in lung vasculature – Prevents O2/CO2 exchange Source: nlm.nih.gov 4 Pulmonary Embolism Risk Factors • Stasis: Immobility (post-surgical, travel, etc.), obesity • Endothelial damage: Surgery, trauma • Hypercoagulability: Oral contraceptive yp g y p pills (OCP), malignancy, genetic disorder Signs/Symptoms • ↑HR, ↑RR, ↑Temp • Pleuritic chest pain MTB S2CK  ‐ p. 401 62-year-old woman with no significant PMH undergoes right total hip replacement 3 days ago. Recovery is uncomplicated until 30 minutes ago, she reported moderate SOB and chest pain with deep inspiration. What’s the next step in evaluating this patient? a. EKG only b. EKG + V/Q Scan c. EKG + Spiral CT scan d. EKG + D-Dimer e. EKG + Heparin Injection  Insensitive for pulmonary embolism No reported contrast allergy Sensitive, but not specific Must diagnose PE first Pulmonary Embolism  Diagnosis • ABG – ↓pO2, ↓pCO2 • EKG – Nonspecific ST-segment and T wave changes • Most common• Most common – S1-Q3-T3 MTB S2CK  ‐ p. 401 Pulmonary Embolism  S1 Q3 T3 Pulmonary Embolism  Diagnosis • ABG – ↓pO2, ↓pCO2 • EKG – Nonspecific ST-segment and T wave changes • Most common• Most common – S1-Q3-T3 • Infrequent during acute PE • Can be found in massive acute PE and cor pulmonale • Spiral CT MTB S2CK  ‐ p. 401 Pulmonary Embolism  Source: James Heilman, MD, commons.wikimedia.org 5 Pulmonary Embolism  Diagnosis • ABG – ↓pO2, ↓pCO2 • EKG – Nonspecific ST-segment and T wave changes • Most common• Most common – S1-Q3-T3 • Infrequent during acute PE • Can be found in massive acute PE and cor pulmonale • Spiral CT – Consider V/Q scan (if IV contrast allergy) MTB S2CK  ‐ p. 401 Pulmonary Embolism  Treatment • Respiratory support • Anticoagulation –Heparin acutely, bridge to warfarin long- termterm –IVC filter (if anticoagulation contraindicated) MTB S2CK  ‐ p. 401 Vascular Abdominal Aortic Aneurysm Aortic Dissection Claudication 69-year-old male with 50 pack-year smoking history is brought to the ER by his wife who reports he seems “confused.” He feels weak and has pain in middle of abdomen. He is a pale, elderly male in moderate distress. BP of 84/55, pulse 120. Palpable, pulsatile mass in patient’s abdomen. What’s the most likely diagnosis? a. Ruptured peptic ulcer b. Hemorrhagic gastritis c. Hemorrhagic pancreatitis d. Ruptured abdominal aortic aneurysm MTB S2CK - p. 399  Would expect peritoneal signs Would expect hematemesis Would expect flank bruising Abdominal Aortic Aneurysm Etiology • Weakening of aortic wall secondary to atherosclerosis – Aortic diameter expands > 1.5x normal – Involves all layers of vessel wall (“True Aneurysm”) – 90% arise from infra- renal aorta MTB S2CK  ‐ p. 399 Source: csm.ornl.gov Abdominal Aortic Aneurysm  Risk Factors • Male > Female • Age • Hypertension, Hyperlipidemia • Smoking Si /S tSigns/Symptoms • Frequently asymptomatic • May report pulsatile abdominal mass MTB S2CK  ‐ p. 399 6 Abdominal Aortic Aneurysm  Diagnosis • CT/MRI – Provides determination of level and surrounding structures • Ultrasound for size Treatment • 3.0-4.0 cm – US every 2-3 years • 4.0-5.4 cm – US or CT every 6-12 months measurements months • ≥ 5.5 cm, asymptomatic – Surgical repair MTB S2CK  ‐ p. 399 Aortic Dissection Etiology • Tearing of aortic intima forms false lumen – Blood flows finto false lumen, extends tear Sopurce: J. Heuser commons.wikimedia.org Aortic Dissection/Etiology • Can occur in ascending or descending aorta Sopurce: J. Heuser commons.wikimedia.org Aortic Dissection Risk Factors • Male > Female • Age > 40 • Hypertension (#1 risk factor) Signs/Symptoms • Sudden onset, “tearing” chest pain – Radiates to the back) • Marfan’s disease, Ehlers-Danlos syndrome • Elevated BP – May be asymmetric (R > L) Aortic Dissection/Diagnosis Demonstration of dissection on imaging • CXR – Widening of mediastinum Aortic Dissection  Source: NNMC 7 Aortic Dissection/Diagnosis Demonstration of dissection on imaging • CXR – Widening of mediastinum • Transesophageal ECHO (TEE) – Acute chest pain and/or clinically unstable • MRA – Chronic chest pain and hemodynamically stable • CT angiogram – TEE and MRI contraindicated Aortic Dissection  Treatment • Ascending dissection = Emergent surgery • Descending dissection = Medical therapytherapy –Beta-Blockers (#1) –Anti-hypertensive meds Claudication Etiology • Atherosclerotic plaques prevent sufficient perfusion to extremities (lower > upper) – Associated with smoking, DM, hyperlipidemia Symptoms • Calf/leg pain with exercise• Calf/leg pain with exercise – Relieved by rest Diagnosis • Ankle-Brachial Index < 0.9 = pathologic < 0.4 = symptomatic Claudication/Management • Medical – Risk Modification • Smoking cessation (#1) – Graded exercise – Pharmacologic therapy Cil t l• Cilostazol • Antiplatelet agents: Aspirin, Clopidogrel • Percutaneous – Stenting, angioplasty • Surgical Shock Trauma Assessment (ABCs) Types of Shockyp Hypovolemic Cardiogenic Neurogenic Septic Anaphylactic Trauma/ABC Assessment • Initial assessment rely on ABC algorithm Airway Breathing Circulation • ABCs are a roadmap, but you must know what to do at each step MTB S2CK  ‐ p. 380‐381 Disability (CNS) Exposure 8 Trauma/ABC Assessment  A = Airway • Must assess for airway compromise – If patient can talk airway is clear – Look for traumatic obstruction, evidence of smoke inhalation • Evaluate need for intubation – Indications • Facial Trauma • Altered Mental Status • Apnea MTB S2CK  ‐ p. 381 Yes Yes  Intubate No Trauma/ABC Assessment Concern for airway compromise? • AMS • Facial trauma • Apnea Facial Trauma? Assess Breathing/ No Yes No MTB S2CK  ‐ p. 381 Cervical Spine Injury? CricothyroidotomyOxygenation Orotracheal Intubation Careful Orotracheal Intubation • Flexible bronchoscopy Trauma/ABC Assessment  B = Breathing • Assess breath sounds • Monitor oxygenation status with pulse oximetry – Goal is O2 Saturation > 90% If O Sat < 90%– If O2 Sat < 90% consider a. Supplemental O2 via nasal cannula b. O2 face mask c. Intubation MTB S2CK  ‐ p. 381 Source:UusiAjaja, commons.wikimedia.org Trauma/ABC Assessment  C = Circulation • Evaluate pulses (distal first, proximal if absent) • Manage hemorrhage sites – Direct pressure slows blood loss • Monitor blood pressure – If the patient is hypotensive, place 2 large- bore IVs and begin aggressive fluid resuscitation – Start with normal saline (only use blood products as secondary measure) MTB S2CK  ‐ p. 381 Trauma/ABC Assessment D = Disability (Altered Mental Status) • Assessed with Glasgow Coma Scale – Eye Response (1-4) – Verbal Response (1-5) – Motor Response (1-6) • Score < 8 requires intubation• Score < 8 requires intubation E = Exposure • Remove all clothing on patient – Assess for hidden injuries • Thorough physical examination 52-year-old woman ejected from her car during a high-speed motor vehicle accident . Upon arrival to ED, she complains of severe, left-sided chest pain. Pale, cool patient in severe distress. Heart rate 130 bpm, BP 86/44 mmHg. JVD along angle of jaw. Chest X-ray shows anterior rib fractures on the left. Which is the most likely diagnosis? a. Hypovolemic shock b. Neurogenic shock c. Anaphylactic shock d. Cardiogenic shock e. Septic shock MTB S2CK  ‐ p. 381  Would not see JVD Warm, flush patients 9 Shock Definition – Inadequate perfusion/oxygenation that impairs organ function Signs/Symptoms • Vitals Signs – Decreased BP – Increased HRIncreased HR • CNS: Confusion, altered mental status • Kidney: Decreased urine output, increased BUN/Cr ratio • Liver: Massively elevated AST/ALT (“Shock Liver”) • Heart: Chest pain, shortness of breath MTB S2CK  ‐ p. 381 Types of Shock  Hypovolemic • Causes: Hemorrhage (#1), Dehydration, Burns MTB S2CK  ‐ p. 382 Source: U.S. Navy photo by Mass Communication Specialist 2nd Class Michael Russell, public.navy.mil Types of Shock/Hypovolemic • Signs/Symptoms – Pale, cold – Trauma • Lab Findings – SVR = ↑ – CVP = ↓ MTB S2CK  ‐ p. 382 CVP = ↓ – PCWP = ↓ – CO = ↓ • Treatment – Aggressive IV fluid replacement – Pressors Types of Shock Cardiogenic • Causes: MI (#1), CHF, arrhythmia • Signs/Symptoms – Pale, cold – Symptoms associated • Lab Findings – CO = ↓ – SVR = ↑ – CVP = ↑ – PCWP = ↑Symptoms associated with MI (Chest pain, SOB) – JVD PCWP ↑ • Treatment – Treat cardiac problem – Do NOT give fluid!!! MTB S2CK  ‐ p. 382 Types of Shock Neurogenic • Causes: CNS damage (cervical/thoracic spinal cord - #1) • Signs/Symptoms: – Warm, flush • Lab Findings – SVR = ↓ – CVP = ↓ – PCWP = ↓ – CO = ↓, – Evidence of CNS damage (trauma) CO ↓ • Treatment – Aggressive IV fluid delivery – Pressors MTB S2CK  ‐ p. 382 Types of Shock Septic • Causes: Infection – E. coli and S. aureus (most common organisms) • Signs/Symptoms – Warm, flush – Possible nidus of infection (UTI, pneumonia, wound) MTB S2CK  ‐ p. 382 Source: cdc.gov 10 Types of Shock/Septic • Lab Findings – SVR = ↓ – CVP = ↓ – CO = ↑ – PCWP = ↔ • Treatment – Broad-spectrum antibiotics – Fluid and pressorsPCWP ↔ • Dopamine • Norepinephrine MTB S2CK  ‐ p. 382 Types of Shock Anaphylactic • Causes: Allergy (insects, food, medication) • Signs/Symptoms – Warm, flushWarm, flush – Wheezing, hives, associated evidence of allergic reaction MTB S2CK  ‐ p. 382 Source: James Heilman, MD, commons.wikimedia.org Types of Shock/Anaphylactic • Lab Findings – CVP = ↓ – SVR = ↓ – PCWP = ↓ – CO = ↑ MTB S2CK  ‐ p. 382 • Treatment – Epinephrine Shock Algorithm Warm/Flush Elevated Decreased Pale/Cold Decreased Elevated Is patient pale/cold or warm/flush? CO change? Hypovolemic • Fluid and pressors PCWP change? Cardiogenic Neurogenic • Fluid and pressors Decreased No Change pressorsCardiogenic • Treat cardiac problem Anaphylactic • Epinephrine Septic • Antibiotics • Fluids and pressors PCWP change? Trauma Abdominal Trauma Thoracic Trauma Pelvic Trauma Abdominal Trauma Penetrating • Gunshot wounds – Must do exploratory laparotomy in ALL patients • Stab wounds – If hemodynamically stable, do a FAST ultrasound scan – If hemodynamically unstable, perform an exploratory laparotomy 11 Abdominal Trauma Diaphragmatic Rupture • Cause – Penetrating or blunt trauma • Left > Right • Symptoms – Respiratory distress – Kehr’s sign = Left shoulder pain • Diagnosis – CXR: Bowel loops in thorax MTB S2CK  ‐ p. 383 Abdominal Trauma Loops Source: Hariharan D, Singhal R, Kinra S, Chilton A, commons.wikimedia.org Absent Hemi-Diaphragm Loops of Bowel Abdominal Trauma/Blunt    Splenic/Liver injury • Causes – Most commonly injured in blunt abdominal trauma • Spleen #1 • Liver #2 – Associated with lower rib fractures • Signs/Symptoms – Hypotension (due to hemorrhage) – Kehr’s sign MTB S2CK  ‐ p. 383 Abdominal Trauma/Blunt  Pancreatic Injury • Causes – Blunt trauma to epigastrum • Bike handlebars • Car dashboard • Signs/Symptoms – Cullen’s sign = Bruising around umbilicus MTB S2CK  ‐ p. 383 Abdominal Trauma/Blunt  MTB S2CK  ‐ p. 383 Source: Herbert L. Fred, MD and Hendrik A. van Dijk, commons.wikimedia.org Abdominal Trauma/Blunt  Diagnosis • FAST scan (ultrasound) – To evaluate for intra- abdominal bleeding • CT scan – If negative FAST but Fluid = Blood If negative FAST, but suspect splenic rupture – To evaluate retroperitoneal bleed MTB S2CK  ‐ p. 383 Source: commons.wikimedia.org 12 Abdominal Trauma/Blunt  Management • If hemodynamically stable… – Close monitoring – Serial abdominal exams IV fluids– IV fluids • If hemodynamically unstable… – Exploratory laparotomy 33-year-old female jogging at night was struck by a drunk driver. She complains of severe abdominal pain that radiates to the back. Vital signs are stable. After ER work-up, patient is admitted for evaluation. Three days later, the following picture is taken. MTB S2CK  ‐ p. 383 Source: Herbert L. Fred, MD and Hendrik A. van Dijk, commons.wikimedia.org 33-year-old female jogging at night was struck by a drunk driver. She complains of severe abdominal pain that radiates to the back. Vital signs are stable. After ER work-up, patient is admitted for evaluation. Three days later, the following picture is taken. What is the most likely diagnosis? a. Pancreatic pseudocyst b. Hemorrhagic pancreatitis c. Ruptured AAA d. Aortic dissection e. Splenic rupture  Delayed appearance No pulsatile mass Stable BP, no chest pain Wrong side, no L shoulder pain Thoracic Trauma   Pneumothorax • Etiology – Air in pleural space  pulmonary collapse • Signs/Symptoms – Chest pain MTB S2CK  ‐ p. 384 – Decreased breath sounds – Hyperresonance to percussion – Tracheal deviation toward affected side Thoracic Trauma/Pneumothorax • Diagnosis – CXR • Treatment Collapsed Lung Border MTB S2CK  ‐ p. 384 Treatment – Chest tube Source: John Yasmer 13 Thoracic Trauma Tension Pneumothorax – A MEDICAL EMERGENCY • Etiology – Chest wall defect acts as “one-way valve” • Air can enter pleural space, but cannot exit • Resulting increase in pressure can compress vital structures – Trachea, vena cava MTB S2CK  ‐ p. 384 Source: army.mil Thoracic Trauma/Tension Pneumothorax Resulting from laceration of cervical trachea and mediastinal pleura Resulting from sucking wound of valvular type a. Laceration of cervical trachea b. Laceration of mediastinal pleura c. Tension pneumothorax d. Collapsed lung e. Shift of heart f. Subcutaneous emphysema g. Partial collapse of contralateral lung a. Valvular sucking wound of chest wall b. Tension pneumothorax c. Collapsed lung d. Cardiac shift to intact side e. Partial collapse of contralateral lung Thoracic Trauma/Tension Pneumothorax   • Signs/Symptoms – Chest pain – Hyperresonance – Decreased breath sounds – Tracheal deviation (away from affected(away from affected side) • Diagnosis – CXR • Treatment – Immediate needle decompression – Chest tube placement MTB S2CK  ‐ p. 384 Source: James G. Smirniotopoulos, M.D. Thoracic Trauma   Hemothorax • Etiology – Blood in pleural space • Signs/Symptomsg y p – Chest pain – Absent breath sounds – Dullness to percussion MTB S2CK  ‐ p. 384 Source: army.mil Thoracic Trauma/Hemothorax • Diagnosis – CXR • Blunted costophrenic angle – CT scan • TreatmentTreatment – Chest tube drainage – Thoracotomy MTB S2CK  ‐ p. 384 Thoracic Trauma/Hemothorax “White-Out” Source: army.mil Posteroanterior CXR made shortly after wounding and showing hemothorax 10 days later, after 6 thoracenteses, three 150 cc of blood and other fluid was removed 14 Hemo/Pneumothorax Diagnosis Symptoms • Chest Pain • Decreased/Absent Breath Sounds Hyperresonance Response to Percussion? Dullness Tracheal Deviation?Hemothorax • Chest tube drainage Pneumothorax • Chest tube Tension pneumothorax • Immediate needle thoracotomy • Chest tube Toward lung Away from lung Thoracic Trauma  Pericardial Tamponade • Etiology – Trauma to pericardium • Broken ribs • Penetrating trauma • Signs/SymptomsSigns/Symptoms – JVD – Hypotension – Decreased heart sounds MTB S2CK  ‐ p. 384 Source: James Heilman, MD, commons.wikimedia.org Thoracic Trauma/Pericardial Tamponade • Diagnosis – EKG • “Electrical Alternans” MTB S2CK  ‐ p. 384 Thoracic Trauma/Pericardial Tamponade • Diagnosis – EKG • “Electrical Alternans” – ECHO • Diagnostic test of choice • Treatment MTB S2CK  ‐ p. 384 – Pericardiocentesis Source: army.mil 26-year-old man suffers blow to chest with a baseball bat. He is brought to the ED with severe right-sided chest pain and difficulty breathing. He is tachypneic at 26 breaths/minute, with a heart rate of 130 beats/minute, diminished breath sounds on the right, and left tracheal deviation. What is the next step in management?What is the next step in management? a. Pericardiocentesis b. Chest X-ray c. Needle thoracotomy d. Chest tube placement e. EKG  Not pericardial tamponade Too slow. This is an emergency Not indicated in this patient 14-year-old boy hits a pothole while riding his bike and falls directly onto the central bar. He presents to the ED with severe groin pain and swelling. Physical examination reveals blood at the urethral meatus and a high-riding prostate. What is the next appropriate step in management? a Place a Foley C f th d tha. Place a Foley b. Get a retrograde urethrogram c. Empiric antibiotics d. CBC and electrolytes e. Discharge the patient with reassurance MTB S2CK  ‐ p. 385  Can further damage urethra Must assess urethral patency 15 The Abdomen ‐ Part 1 Abdominal Pain Mesenteric Ischemia Esophageal Pathology Gastric Perforation Abdominal Pain Differential Diagnosis RUQ • Cholecystitis - Radiates to R shoulder • Cholangitis • Perforated Ulcer LUQ • Splenic Rupture - Radiates to L shoulder • Ischemic Bowel Disease Mid-Epigastrum • Pancreatitis MTB S2CK  ‐ p. 387 RLQ • Appendicitis • Ovarian Torsion (♀) • Ectopic Pregnancy (♀) • Diverticulitis (Cecal) LLQ • Diverticulitis (Sigmoid) • Sigmoid Volvulus • Ovarian Torsion (♀) • Ectopic Pregnancy (♀) • Peptic Ulcer Disease • Aortic Dissection - Radiates to back 66-year-old man in the ED with acute onset, severe abdominal pain. Abdominal exam benign, without guarding or rebound tenderness. White count 18,000/mm3 (4,500-11,000/mm3), lactic acid 4.2 mg/dL (4.5 to 19.8 mg/dL). Only medication is coumadin. What’s the most appropriate next step in management? MRI f th bd T k t la. MRI scan of the abdomen b. Exploratory Laparotomy c. Colonoscopy d. Oral antibiotics e. EKG  Takes too long Risk of bowel perforation Doesn’t treat primary concern Symptoms not consistent with cardiac etiology Etiology • Mesenteric artery atherosclerosis  insufficient blood flow to bowel Chronic Mesenteric Ischemia A lack of blood flow causes ischemia to the bowel wall and sloughing of the mucosa. Source: Niket Sonopal, MD. – Patients often have other atherosclerotic diseases • Angina • Claudication MTB S2CK  ‐ p. 385‐386 Chronic Mesenteric Ischemia Signs/Symptoms • Diffuse, postprandial abdominal pain – Severe, crampy, associated nausea – Due to  O2 requirement by gut after meals – May lead to weight loss due to fear of eating • Bloody diarrhea • Progressive disease begins with mild ischemia, progresses to full occlusion of blood flow MTB S2CK  ‐ p. 386 Chronic Mesenteric Ischemia   Diagnosis • CT abdomen (initial test) – Fast, non-invasive • CT angiography is most accurate Treatment Surgical revascularization via arterial bypass• Surgical revascularization via arterial bypass – NPO – Hydration with IV fluids – Bowel prep 24 hours preceding surgery • Nitrates may provide short-term symptom improvement MTB S2CK  ‐ p. 386 16 Acute Mesenteric Ischemia Etiology • Acute occlusion of mesenteric arteries – Most commonly the superior mesenteric – Causes: • Embolism secondary to A fib (#1)• Embolism secondary to A-fib (#1) MTB S2CK  ‐ p. 386 Acute Mesenteric Ischemia Source: Mikael Häggström from original image created and uploaded by Dr. I-Chen Tsai, commons.wikimedia.org Acute Mesenteric Ischemia Etiology • Acute occlusion of mesenteric arteries – Most commonly the superior mesenteric – Causes: • Embolism secondary to A fib (#1)• Embolism secondary to A-fib (#1) • Acute thrombus formation on atherosclerotic plaque • Results in bowel infarction – Splenic flexure (#1) and hepatic flexure (#2) are most common sites MTB S2CK  ‐ p. 386 Acute Mesenteric Ischemia Signs/Symptoms • Sudden onset, severe abdominal pain – “Pain out of proportion to exam” • Nausea, vomiting Diagnosis • Labs: ↑WBC, ↓pH, ↑Lactate • Abdominal X-ray/CT – Air in bowel wall (“Pneumatosis , g • Bloody diarrhea ( Intestinalis”) – Edema – Ileus • CT angiography (Most accurate) Acute Mesenteric Ischemia Mesenteric artery thromboembolism. Source: Joel McFarland, Medpix 28818 Acute Mesenteric Ischemia   Treatment – Emergent Laparotomy • Resection of necrotic bowel MTB S2CK  ‐ p. 386 17 Acute Mesenteric Ischemia Source: haitham alfalah, commons.wikimedia.org 52-year-old woman, alcoholic, with severe chest pain after an episode of persistent vomiting. No blood in vomitus, only stomach contents. Exam reveals crepitus over upper anterior chest wall. What is the next step? a. Ethanol level Not useful in this case b. Chest X-Ray c. Upper Endoscopy d. Barium Esophagogram e. Gastrografin Esophagogram MTB S2CK  ‐ p. 387  Will not show esophageal rupture Risk further perforation Not water-soluble Esophageal Injuries Mucosal Tear “Mallory‐Weiss Syndrome” Esophageal Perforation “Boerhaave Syndrome” Cause Symptoms Vomiting/Retching • Alcoholics Hematemesis Odynophagia Iatrogenic is #1 (Endoscopy) Vomiting/Retching • Alcoholics Retrosternal chest pain • Severe, acute onset • Radiates to L shoulder • Subcutaneous Emphysema Location Diagnosis Treatment Complications Gastroesophageal junction Gastrografin esophagogram • No leakage Supportive Cauterization if necessary Rare • Subcutaneous Emphysema Distal esophagus • Left Posterolateral Aspect Gastrografin esophagogram • Leakage Emergent Surgery • High mortality (25%) Acute mediastinitis • Very high mortality MTB S2CK  ‐ p. 387‐388 57-year-old male with BMI of 37 (18.5-24.9 normal) presents to ED with weakness. Vomiting large amounts of blood twice in last hour and passing one bright red stool. He has persistent pain in his mid-abdomen. Takes omeprazole for heartburn. BP 100/60, HR 120. What is the diagnosis? a Gastric Perforation N bl d P it l ia. Gastric Perforation b. Hemorrhagic ulcer c. Boerhaave’s syndrome d. Diverticulosis e. Acute mesenteric ischemia  No bleed. Peritoneal signs. No hematemesis No hematochezia No hematemesis Gastric Perforation Etiology • Secondary to peptic ulcer disease – Increased production of gastric acid, combined with compromise of stomach lining results in ulcer formation MTB S2CK  ‐ p. 388 Source: commons.wikimedia.org Gastric Perforation Risk Factors • H. Pylori infection • NSAIDs • Burns • Trauma• Trauma • Head trauma • Cancer • Ethanol • Tobacco MTB S2CK  ‐ p. 388 Source: User:KGH, commons.wikimedia.org 18 Gastric Perforation   Pathophysiology • Perforation – Ulcer completely erodes through visceral wall • Gastric contents are released into abdominal • Hemorrhage – Ulcer erodes into gastroduodenal artery • More common than gastric perforation Seen with posteriorreleased into abdominal cavity • Result is damage to peritoneal structures – Peritonitis (anterior + posterior ulcers) – Pancreatitis (posterior ulcers) • Seen with posterior ulcers • Requires upper endoscopy to evaluate/treat bleed MTB S2CK  ‐ p. 388 Gastric Perforation/Signs and Symptoms • Acute onset mid-epigastric abdominal pain – May radiate to right shoulder (phrenic nerve involvement) – Worsening over time • Peritoneal signs (if any delay in seeking t t t)treatment) – Rigidity – Guarding – Rebound tenderness MTB S2CK  ‐ p. 389 Gastric Perforation  Diagnosis • Upright chest X-ray – Free air underunder diaphragm • Abdominal CT MTB S2CK  ‐ p. 389 Source: commons.wikimedia.org Gastric Perforation 1) Make Patient NPO • Prevents further extrusion of gastric contents into peritoneal cavity 2) Place NG Tube • Suction gastric contents • Mitigates risk from newly formed acid Management MTB S2CK  ‐ p. 389 • Mitigates risk from newly-formed acid 3) Medical Management • Broad-spectrum antibiotics to combat infection • IV fluids in preparation for surgery 4) Emergent Surgery • Exploratory laparotomy - Repair perforation The Abdomen ‐ Part 2 Abdominal Abscess Inflammatory GI Conditions Abdominal Obstruction 16-year-old boy comes with new onset RLQ pain. He reports vague, mid-abdominal pain for last day, but when he awoke this morning it was much sharper and had changed location. He displays guarding and rebound tenderness, and palpation of LLQ hurts on right side. WBC count of 16,000/mm3 (4,500- 11 000/ 3)11,000/mm3) What is the next step in management? a. Abdominal X-ray b. Colonoscopy c. RLQ Ultrasound d. Laparoscopic Appendectomy MTB S2CK  ‐ p. 389  Non-specific findings Risk of perforation Non-specific findings 19 Male Female No Right Lower Quadrant Pain Age > 60 yo? Cecal Diverticulitis • Make NPO, Place NG Tube • Broad-Spectrum Abx Male or Female? Order β-HCG, Pelvic US Yes Elevated or Abnormal Normal Appendicitis • Emergent Laparoscopic Appendectomy Ectopic Pregnancy • Emergent Surgery Ovarian Torsion • Doppler US to diagnosis • Laparoscopic surgery Abdominal Abscess Cause • Surgical complication (#1) • Inflammatory disease • Trauma Signs/SymptomsSigns/Symptoms • Abdominal pain/distension • Non-specific symptoms – Fever/chills – GI symptoms – nausea/vomiting, diarrhea • Rectal fullness MTB S2CK  ‐ p. 390 Abdominal Abscess Diagnosis • Abdominal CT – Visual evidence of abscess – Information about surrounding structures MTB S2CK  ‐ p. 390 Abdominal Abscess Source: Joel McFarland, Medpix 28716 Abdominal Abscess Diagnosis • Abdominal CT – Visual evidence of abscess – Information about surrounding structures • CBCCBC – May show elevated WBC count Treament • Broad-Spectrum Antibiotics • Incision + Drainage – Percutaneous (CT-guided) versus Open MTB S2CK  ‐ p. 390 78-year-old woman with severe LLQ pain, fever, and anorexia of one day. She’s had dark, tarry stools in the past. The patient’s husband brings in a medication list, which includes a stool softener and iron supplements. She displays guarding and rigidity. What is the diagnosis? a Ectopic pregnancy P ti t i t la. Ectopic pregnancy b. Acute appendicitis c. Cholecystitis d. Acute diverticulitis e. Acute pancreatitis  Patient is postmenopausal Rare in elderly, RLQ in location RUQ pain Central abd pain, radiates to back 20 Inflammatory GI Conditions Appendicitis Pancreatitis Diverticulitis Cholecystitis Fecolith  obstructing  appendiceal  orifice Anorexia Fever Periumbilical   Pain  RLQ Alcohol  Gallstone  obstructing  pancreatic duct N/V Fever Abdominal Pain • Radiates to      back Fecal  obstruction of  bowel wall out‐ pouchings N/V Fever LLQ Pain Gallstone  obstructing cystic  duct N/V Fever RUQ pain • Worse with  inspiration Cause Symptoms MTB S2CK  ‐ p. 391 Phys. Exam CT Scan Laparoscopic  Removal Abscess back Amylase/Lipase CT Scan (#1) IV Fluids NPO Pseudocyst CT Scan Antibiotics (x1) Resection (if  recurrent) Abscess inspiration Ultrasound • Fluid, Stones,  Thick Wall HIDA scan (#1) Laparoscopic  Removal Perforation Diagnosis Treatment Complication 55 year-old man presents to the ED with severe, intermittent abdominal pain and nausea/vomiting. He cannot recall when he last passed flatus, but is certain he didn’t have a bowel movement this morning. He has type 1 diabetes and had an open appendectomy in his 30s. Temperature of 101.8. Loud, high-pitched bowel sounds noted on auscultation. An abdominal plain film shows a partial small bowel obstruction. What is the best next step in management? a. Prescribe a laxative b. Place an NG-tube c. Emergent exploratory laparotomy d. Prescribe antibiotics e. Perform a colonoscopy  Will not relieve obstruction (may worsen) Medical management first No evidence of bowel perforation Will not relieve obstruction Bowel Obstruction Pathophysiology • A mechanical or functional obstruction of intestines – Leads to fluid/gas accumulation proximal f • Obstruction can be partial or complete – Partial = GI contents are able to pass obstruction site to site of obstruction – Resulting pressure increase leads to 1. Pain 2. Decreased perfusion (and risk of necrosis) – Complete = No avenue for passage • Represents a much more severe condition MTB S2CK  ‐ p. 392 Bowel Obstruction   Causes/Risk Factors • Adhesions from previous abdominal surgery – #1 in developed countries • Neoplasms • Intussusception = “Telescoping bowel” – Most frequently seen in pediatric population • Hernia – #1 in undeveloped countries • Volvulus = “Twisting of bowel on its mesentery” • Crohn’s disease • Foreign bodies • Intestinal atresia = “Blind Pouch” – Only seen in neonates MTB S2CK  Only ‐ p. 393 Bowel Obstruction  Signs/Symptoms • Severe, crampy abdominal pain – Colicky in nature • Nausea/vomiting Diagnosis • Labs – ↑WBC, ↑ Lactate, ↓pH • Abdominal X-ray • Fever • High-pitched, “Tinkling” bowel sounds – Air-fluid levels, dilated loops of bowel MTB S2CK  ‐ p. 392‐393 Bowel Obstruction  Source: James Heilman, MD, commons.wikimedia.org 21 Bowel Obstruction  Signs/Symptoms • Severe, crampy abdominal pain – Colicky in nature • Nausea/vomiting • Fever Diagnosis • Labs – ↑WBC, ↑Lactate, ↓pH • Abdominal X-ray – Air-fluid levels, dilated loops of bowel• Fever • High-pitched, “Tinkling” bowel sounds loops of bowel • Abdominal CT w/ oral contrast (#1) – Clear transition zone correlates with obstruction MTB S2CK  ‐ p. 392‐393 Bowel Obstruction  1) Make Patient NPO • Prevents further increase in bowel pressure 2) Place an NG Tube (w/suction) • Lowers bowel pressure proximal to obstruction Management MTB S2CK  ‐ p. 393 3) Medical Management • IV Fluids • Volume is lost due to third-spacing 4) Surgical Decompression (if indicated) • Complete obstruction (Emergent) • Lack of improvement with medical management Orthopedics Fracture Types Upper Extremity Injuriespp y j Back Pain Fat Embolism Compartment Syndrome Knee Injuries Fractures Algorithm Symptoms: • Pain • Swelling • Bony deformity Timing: • Acute onset with trauma X-rays Neurovascular exam +Presentation Diagnosis + MTB S2CK  ‐ p. 393‐394 Surgery (ORIF) Closed reduction Management Open (skin puncture) Closed (skin intact) Emergency surgery (I&D) Fracture Types  Stress Fractures • Cause – Overuse injury secondary to repetitive insult to bone • Presentation Clue – High-performance athlete Common sites– Common sites 1. Metatarsals 2. Tibia • Diagnosis – CT/MRI • Treatment – Rest and rehabilitation MTB S2CK  ‐ p. 394 Fractures Types   Compression Fractures • Cause – Vertebral fracture associated with poor bone quality • Osteoporosis (classical example)p ( p ) • Presentation Clue – Elderly patient with back pain • 33% thoracic spine, 33% thoracolumbar, 33% lumbar MTB S2CK  ‐ p. 394 22 Fractures Types/Compression Fractures Diagnosis • X-ray • CT, if inconclusive Source:commons.wikimedia.org Treatment • Controversial MTB S2CK  ‐ p. 394 Fractures Types   Pathologic Fractures • Cause – Fracture in bone weakened by disease • Metastatic cancer • Multiple myeloma • Diagnosis – X-ray • Treatment – Treat fracture – ID & treat primary• Paget’s disease • Presentation Clue – Patient with fracture after minimal trauma ID & treat primary disease MTB S2CK  ‐ p. 394 Upper Extremity Injuries    Clavicle Fracture • Cause – History of fall – Blunt shoulder trauma • Presentation Clue MTB S2CK  ‐ p. 395 Presentation Clue – Pain over anterior shoulder – Clavicle “step-off” Upper Extremity Injuries/Clavicle Fracture • Workup – X-ray – Careful distal neurovascular exam • Must rule out subclavian artery/brachial plexus injury • Treatment – Arm sling MTB S2CK  ‐ p. 395 Source: Mark D. Travis Upper Extremity Injuries   Anterior Shoulder Dislocation • Cause – Fall on outstretched hand – Sports, blunt trauma • Signs/Symptoms MTB S2CK  ‐ p. 395 Signs/Symptoms – Severe shoulder pain, swelling – Arm is held in external rotation Upper Extremity Injuries/ Anterior Shoulder Dislocation • Diagnosis – X-ray, MRI (if necessary) – Careful distal neurovascular exam • Must rule out axillary artery or nerve injury • Treatment – Reduction w/sling immobilization MTB S2CK  ‐ p. 395 Source: Daniel Patrick Moloney 23 Upper Extremity Injuries   Posterior Shoulder Dislocation • Cause – History of seizure or electric shock • Signs/Symptoms MTB S2CK  ‐ p. 395 g y p – Severe shoulder pain, swelling – Arm is held in internal rotation Upper Extremity Injuries/ Posterior Shoulder Dislocation • Diagnosis – XR, MRI (if necessary) • Treatment Source: Medpix 20030 – Reduction w/sling immobilization MTB S2CK  ‐ p. 395 19-year old with persistent wrist pain of 3 days duration. Pain began when he braced himself from a fall. Right wrist is notable for point tenderness and mild swelling at base of dorsal aspect of thumb, but no deformity. An X-ray is shown on the next slide. Source: Medpix 6094 19-year old with persistent wrist pain of 3 days duration. Pain began when he braced himself from a fall. Right wrist is notable for point tenderness and mild swelling at base of dorsal aspect of thumb, but no deformity. An X-ray is shown below. What is the best next step in management? a. Reassurance b. MRI Scan c. Thumb Spica Cast d. Amputation e. Open Reduction + Internal Fixation  Scaphoid may be fractured Unnecessary, worse than CT No indication No fracture (yet) Upper Extremity Injuries Trigger finger • Cause – Inflammation of finger flexor pulley system • Leads to “catching/locking” of flexor tendon • Signs/Symptoms – Lone digit caught in flexion MTB S2CK  ‐ p. 395 Lone digit caught in flexion • “Popping” sensation if digit is manually extended – Moderate–severe pain • Diagnosis – Clinical Exam • Treatment – Corticosteroid injection 24 Upper Extremity Injuries    Dupuytren’s Contracture • Cause – Thickening of palmar fascia, leading to flexion contracture • Digits cannot fully extend MTB S2CK  ‐ p. 395 Source: commons.wikimedia.org Upper Extremity Injuries/ Dupuytren’s Contracture • Risk Factors – Male > Female – Age > 40 – Northern European descent Di i MTB S2CK  ‐ p. 395 • Diagnosis – Clinical Exam • Treatment – Surgery A 66-year-old man comes to his PCP with bilateral leg pain of several months duration. The pain seems to be worst when he has to walk several blocks, and improves when he sits down. Leaning forward (on a bench, shopping cart, etc.) alleviates the pain. He is a non-smoker. What is the most appropriate next diagnostic step? a. Lower Extremity XR b. Doppler US of the calf c. Ankle-Brachial Indices d. Spine MRI e. Leg MRI Useful for bony trauma Useful for DVT evaluation Diagnoses claudication Useful for soft-tissue injury/stress fractures Back Pain Spinal Stenosis • Cause – Arthritic changes result in narrowing of spinal canal • Lumbar #1, Cervical #2 • Symptoms• Symptoms – Neck/Back Pain – Bilateral leg/buttock pain + numbness • “Pseudo-claudication” • Worse with walking, improves with spine flexion Back Pain/Spinal Stenosis • Diagnosis – MRI • Treatment – NSAIDs vs. surgeryg y Source: nih.gov, commons.wikimedia.org Back Pain   Herniated Disk Disease Cause • Intervertebral disk herniates, compressing spinal nerve root – Often associated with lifting injury – Most frequently seen in elderly Symptoms • “Electric” Pain following a dermatome distribution 25 Back Pain/Herniated Disk Disease Source: user:debivort, commons.wikimedia.org Back Pain/Herniated Disk Disease Diagnosis • Clinical Exam (“Straight Leg Raise”) – Consider MRI if red flags present Treatment • NSAIDS, Activity Modification Source:Mjorter, commons.wikimedia.org Back Pain   Red Flags – Concern for Metastasis or Abscess Pain not relieved by rest – Not worse with activity Fever Neurological deficits – Bowel/Bladder Night pain Constant, dull pain > 6 weeks Bowel/Bladder incontinence – Abnormal reflexes History of Cancer Back Pain   • Management – MRI to evaluate for mass lesion – Emergent glucocorticoids if neurological findings 22-year-old woman was struck by a car 3 days ago while walking her dog. The impact broke her femur, which required immediate surgical repair. This morning the patient is confused and has difficulty catching her breath. ABG shows PaO2 55 mmHg, and exam reveals a petechial rash. What is the most likely diagnosis?What is the most likely diagnosis? a. Myocardial infarction b. Pancreatitis c. Rhabdomyolysis d. Fat embolism MTB S2CK  ‐ p. 396  No rash Expect abdominal pain No hypoxemia Fat Embolism – A Medical EMERGENCY Etiology • Traumatic long bone fracture (#1 = Femur) – Releases marrow fat into circulation – Fat vesicles are tooFat vesicles are too large to pass through capillaries • Result is vascular occlusion MTB S2CK  ‐ p. 396 H&E stain, lung’s blood vessel with fibrinoid material and an optical empty space indicative of the presence of lipid. Source: Boris L Kanen, Ruud JLF Loffeld, commons.wikimedia.org 26 Fat Embolism Signs/Symptoms – Onset 0-5 days after fracture • Respiratory Distress (V/Q mismatch) – SOB – Tachypnea MTB S2CK  ‐ p. 396 yp • Confusion (Involves brain vasculature) • Petechial Rash (Involves skin capillaries) – Chest wall, upper extremities Fat Embolism   Diagnosis • ABG: PO2 < 60 mmHg • CBC: Decreased platelet count • Chest X-ray: Infiltrates • Urinalysis: Fat droplets in urine T t t MTB S2CK  ‐ p. 396 Treatment • Respiratory Support – Goal O2 Sat > 90% – Consider intubation/mechanical ventilation if severely hypoxic Compartment Syndrome Pathophysiology • Injury occurs, resulting in swelling… – Fracture #1 (tibial, forearm) – Burns • Pressure builds, leading to severe tissue compression – Nerves – Muscle – Crush injuries (Reperfusion syndrome) • In closed compartment (fascial sheath, cast), there’s no escape for increasing pressure – Vessels • Resulting damage can lead to Volkmann’s ischemic contracture, limb loss, or death MTB S2CK  ‐ p. 396 Compartment Syndrome/Signs & Symptoms   Pain Parathesias PulselessnessPoikilothermia Early Findings Late Findings Severe, worse “Pins and needles” Cold, due to decreased Absent distal pulses The 6 P’s MTB S2CK  ‐ p. 396‐397 Paralysis Pallor with muscle stretch Pale skin from  blood flow nerve involvement blood flow Inability to move distal musculature (ominous finding) Compartment Syndrome   Treatment – A Medical EMERGENCY • Surgical fasciotomy –Releases compartment p pressure MTB S2CK  ‐ p. 397 Source: Sarte, commons.wikimedia.org • Basic Principles – Ligamentous/meniscal knee injuries have similar symptoms • Knee Pain • Swelling • Instability Knee Injuries  The key factor is time course in which symptoms present – Pay attention to mechanism of injury! – Physical exam provides clues to etiology • Special tests for each type of knee injury – Diagnostic test of choice is always MRI 27 Knee Injuries  Mechanism of  Injury Symptom  Onset Exam  Maneuver Management Trauma to  contralateral  aspect of knee Twisting or  direct impact Immediate Immediate and  Severe Medial/Lateral  Instability Anterior Drawer  sign Lachman Test Conservative Arthroscopic  Repair MCL/LCL  Injury ACL Tear MTB S2CK  ‐ p. 398 Forced  Hyperextension Twisting Injury Immediate but  Mild Delayed (12‐24  hours) Lachman Test Posterior  Drawer sign Joint line  tenderness McMurray’s  Clicking/Locking Repair vs.  Conservative  management Conservative PCL Tear Meniscal  Tear 22-year-old hockey star is checked by an opposing player, and his leg gets tangled as he falls. He experiences a “popping” sensation in his left knee, which immediately swells. The team physician performs a physical exam and notes a positive anterior drawer sign as well as medial knee instability. He recommends an MRI to evaluate the likely ACL and MCL tears. MTB S2CK  ‐ p. 398 MRI to evaluate the likely ACL and MCL tears. What other structure will likely be injured on MRI? a. Lateral Collateral Ligament b. Lateral Meniscus c. Medial Meniscus d. Posterior Cruciate Ligament  Different injury mechanism ALL S2HY_ALLG_01.pdf ALL S2HY_CARD_01 ALL S2HY_DERM_01 ALL S2HY_EMRG_01 ALL S2HY_ENDO_01 ALL S2HY_ETHI_01 ALL S2HY_GAST_01 ALL S2HY_HEME_01 ALL S2HY_INFD_01 ALL S2HY_NEPH_01 ALL S2HY_NEUR_01 ALL S2HY_OBGY_01 ALL S2HY_ONCO_01 ALL S2HY_OPTH_01 ALL S2HY_PEDS_01 ALL S2HY_PSYH_01 ALL S2HY_PULM_01 ALL S2HY_PVNT_01 ALL S2HY_RADI_01 ALL S2HY_RHUM_01 ALL S2HY_SURG_01