First_Aid_Step2

First_Aid_Step2. Database of High-Yield Facts The seventh edition of First Aid for the USMLE Step 2 CK contains a revised and expanded database of clinical material that student authors and faculty have identified as high yield for boards review. The facts are organized according to subject matter, whether medical specialty (e.g., Cardiovascular, Renal) or high-yield topic (e.g., Ethics) in medicine. Each subject is then divided into smaller subsections of related facts. Individual facts are generally presented in a logical approach, from basic definitions and epidemiology to History/Physical Exam, Diagnosis, and Treatment. Lists, mnemonics, and tables are used when helpful in forming key associations.


First_Aid_Step2

First_Aid_Step2. The content is mostly useful for reviewing material already learned. This section is not ideal for learning complex or highly conceptual material for the first time. Black-and-white images appear throughout the text. In some cases, reference is made to the “clinical image” section at the end of Section 2, which contains full-color glossy plates of histology and patient pathology by topic. At the end of Section 2, we also feature a Rapid Review chapter of key facts and classic associations to cram a day or two before the exam. The Database of High-Yield Facts is not comprehensive. Use it to complement your core study material and not as your primary study source. The facts and notes have been condensed and edited to emphasize the essential material. Work with the material, add your own notes and mnemonics, and recognize that not all memory techniques work for all students.


First_Aid_Step2

First_Aid_Step2. We update Section 2 biannually to keep current with new trends in boards content as well as to expand our database of high-yield information. However, we must note that inevitably many other high-yield entries and topics are not yet included in our database. We actively encourage medical students and faculty to submit entries and mnemonics so that we may enhance the database for future students. We also solicit recommendations of additional tools for study that may be useful in preparing for the examination, such as diagrams, charts, and computer-based tutorials (see How to Contribute, p. xv).


First_Aid_Step2

First_Aid_Step2. The entries in this section reﬂect student opinions of what is high yield. Owing to the diverse sources of material, no attempt has been made to trace or reference the origins of entries individually. We have regarded mnemonics as essentially in the public domain. All errors and omissions will be gladly corrected if brought to the attention of the authors, either through the publisher or directly by e-mail. To evaluate patients for cardiac abnormalities, methodically assess the ECG for rate, rhythm, axis, intervals, waveforms, and chamber enlargement (see Figures 2.1-1 and 2.1-2). The normal heart rate is 60–100 bpm. A rate < 60 bpm is bradycardia; > 100 bpm is tachycardia. Look for sinus rhythm (P before every QRS and QRS after every P), irregular rhythms, junctional or ventricular rhythms (no P before a QRS), and ectopic beats. Normal: An upright (positive) QRS in leads I and II (–30 degrees to +105 degrees).


First_Aid_Step2

First_Aid_Step2. Normal: An upright (positive) QRS in leads I and II (–30 degrees to +105 degrees). Left-axis deviation: An upright QRS in lead I and a downward (negative) QRS in lead II (< –30 degrees). Right-axis deviation: A downward QRS in lead I and an upright QRS in lead II (> +105 degrees). II aVRI III aVL aVF V1 V2 V3 V4 V5 V6 F IGU R E 2.1 -1. Normal electrocardiogram from a healthy subject. Quickly estimate heart rate by counting the number of large boxes subtended by two consecutive QRS complexes, as follows: 300-150-100-75-6050-30 bpm. An upright QRS in leads I and ll—the “double thumbs-up” sign—signif es a normal axis.


First_Aid_Step2

First_Aid_Step2. An upright QRS in leads I and ll—the “double thumbs-up” sign—signif es a normal axis. Sinus rhythm is present with a heart rate of 75 bpm. The PR interval is 0.16 sec; the QRS interval (duration) is 0.08 sec; the QT interval is 0.36 sec; QTc is 0.40 sec; and the mean QRS axis is about +70 degrees. The precordial leads show normal R-wave progression with the transition zone (R wave = S wave) in lead V3. (Reproduced, with permission, from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008: Fig. 221-7.) Time (s) 1.0 0.5 0 -0.5 0 0.2 0.4 0.6 P T S Q U Isoelectric line ST segment PR interval QT interval Potential (mV) Action potential QRS P T 0.2 0.4 0.6 Time (s) SA node "pacemaker" inherent dominance with slow phase of upstroke AV node 100-msec delay atrioventricular delay F IGU R E 2.1 -2. Electrocardiogram measurements. WiLLiaM MaRRoW: W pattern of QRS in V1–V2 and M pattern of QRS in V3–V6 for LBBB


First_Aid_Step2

First_Aid_Step2. F IGU R E 2.1 -2. Electrocardiogram measurements. WiLLiaM MaRRoW: W pattern of QRS in V1–V2 and M pattern of QRS in V3–V6 for LBBB M pattern of QRS in V1–V2 and W pattern of QRS in V3–V6 for RBBB Normal: PR interval between 120 and 200 msec and QRS < 100 msec. Atrioventricular (AV) block: PR interval > 200 msec, or P with no QRS afterward. Left bundle branch block (LBBB): QRS duration > 120 msec; no R wave in V1; wide, tall R waves in I, V5, and V6. Right bundle branch block (RBBB): QRS duration > 120 msec; RSR′ complex (“rabbit ears”); qR or R morphology with a wide R wave in V1; QRS pattern with a wide S wave in I, V5, and V6. Long QT syndrome: QTc > 440 msec. An underdiagnosed congenital disorder that predisposes to ventricular tachyarrhythmias. Ischemia: Inverted T waves; poor R-wave progression in precordial leads; ST-segment changes (elevation or depression).


First_Aid_Step2

First_Aid_Step2. Ischemia: Inverted T waves; poor R-wave progression in precordial leads; ST-segment changes (elevation or depression). Transmural infarct: Significant Q waves (> 40 msec or more than one-third of the QRS amplitude). ST elevation; T-wave inversion; the presence of possible impending infarction based on plaque instability. ■Atrial hypertrophy: Right atrial abnormality if P-wave amplitude in lead II is < 2.5 mm; left atrial abnormality if P-wave width in lead II is > 120 msec, or if terminal negative deﬂ ection in V1 is > 1 mm in amplitude and > 40 msec in duration. F IGU R E 2.1 -3. Left ventricular hypertrophy. Shown are leads V1, V2, V5, and V6. S wave in V2 + R wave in V5 = 55 mm. Note ST changes and T-wave inversion in V5 and V6, suggesting strain. (Reproduced, with permission, from Gomella LG et al. Clinician’s Pocket Reference, 11th ed. New York: McGraw-Hill, 2006: Fig. 19-27.) Left ventricular hypertrophy (LVH; see Figure 2.1-3):


First_Aid_Step2

First_Aid_Step2. Left ventricular hypertrophy (LVH; see Figure 2.1-3): Cornell criteria: Amplitude of R in aVL + S in V3 > 28 mm in men or > 20 mm in women. Sokolow-Lyon criteria: S in V1 + R in V5 or V6 > 35 mm. Right ventricular hypertrophy (RVH): Right-axis deviation and an R wave in V1 > 7 mm. Key exam findings that can narrow the differential include the following: Jugular venous distention (JVD, > 7 cm above sternal angle): Suggests right heart failure, pulmonary hypertension, volume overload, tricuspid regurgitation, or pericardial disease. Hepatojugular reﬂ ux: Fluid overload; impaired right ventricular compliance. Kussmaul’s sign (↑ in JVP with inspiration): Right ventricular infarction, postoperative cardiac tamponade, tricuspid regurgitation, constrictive pericarditis. Systolic murmurs: Aortic stenosis: Harsh systolic ejection murmur; radiation to carotids. Mitral regurgitation: Holosystolic murmur; radiation to axillae or to carotids.


First_Aid_Step2

First_Aid_Step2. Systolic murmurs: Aortic stenosis: Harsh systolic ejection murmur; radiation to carotids. Mitral regurgitation: Holosystolic murmur; radiation to axillae or to carotids. Mitral valve prolapse: Midsystolic or late-systolic click. Flow murmur: Very common, and does not imply cardiac disease. Diastolic murmurs: Always abnormal. Aortic regurgitation: Early decrescendo murmur. Mitral stenosis: Midto late, low-pitched murmur. Heart auscultation locations from the upper right sternal border, upper left sternal border, lower left sternal border, and apex: All (Aortic) People (Pulmonic) Try (Tricuspid) McDonald’s (Mitral). Causes of CHF— Hypertension Endocrine Anemia Rheumatic heart disease Toxins Failure to take meds Arrhythmia Infection Lung (pulmonary Gallops: S3 gallop: Dilated cardiomyopathy (ﬂoppy ventricle), mitral valve disease; often normal in younger patients and in high-output states (e.g., pregnancy).


First_Aid_Step2

First_Aid_Step2. Gallops: S3 gallop: Dilated cardiomyopathy (ﬂoppy ventricle), mitral valve disease; often normal in younger patients and in high-output states (e.g., pregnancy). S4 gallop: Hypertension, diastolic dysfunction (stiff ventricle), aortic stenosis; often normal in younger patients and athletes. Edema: Pulmonary: Left heart failure. Peripheral: Right heart failure and biventricular failure, peripheral venous disease, constrictive pericarditis, tricuspid regurgitation, hepatic disease, lymphedema; also nephrotic syndrome, hypoalbuminemia, and drugs. Peripheral pulses: ■↑: Compensated aortic regurgitation, coarctation (arms > legs), patent ductus arteriosus. ■↓: Peripheral arterial disease. Pulsus paradoxus (↓ systolic BP with inspiration): Pericardial tamponade; also asthma and COPD, tension pneumothorax, foreign body in airway. Pulsus alternans (alternating weak and strong pulses): Cardiac tamponade, impaired left ventricular systolic function; poor prognosis.


First_Aid_Step2

First_Aid_Step2. Pulsus alternans (alternating weak and strong pulses): Cardiac tamponade, impaired left ventricular systolic function; poor prognosis. Pulsus parvus et tardus (weak and delayed pulse): Aortic stenosis. Table 2.1-1 outlines the etiologies, clinical presentation, and treatment of common bradyarrhythmias and conduction abnormalities. Tables 2.1-2 and 2.1-3 outline the etiologies, clinical presentation, and treatment of common supraventricular and ventricular tachyarrhythmias.


First_Aid_Step2

First_Aid_Step2. Tables 2.1-2 and 2.1-3 outline the etiologies, clinical presentation, and treatment of common supraventricular and ventricular tachyarrhythmias. Defined as a clinical syndrome caused by the inability of the heart to pump enough blood to maintain ﬂuid and metabolic homeostasis. Risk factors include coronary artery disease (CAD), hypertension, cardiomyopathy, valvular heart disease, and diabetes. The American Heart Association/American College of Cardiology (AHA/ACC) guidelines classify heart failure according to clinical syndromes, but alternative classification systems include functional severity, left-sided vs. right-sided failure, and systolic vs. diastolic failure (see Tables 2.1-4 through 2.1-7). T AB LE 2.1 -1. Bradyarrhythmias and Conduction Abnormalities


First_Aid_Step2

First_Aid_Step2. Sinus bradycardia Normal response to cardiovascular conditioning; can also result from sinus node dysfunction or from β-blocker or calcium channel blocker (CCB) excess. May be asymptomatic, but may also present with lightheadedness, syncope, chest pain, or hypotension. Ventricular rate < 60 bpm; normal P wave before every QRS complex. None necessary if asymptomatic; atropine may be used to ↑ heart rate; pacemaker placement is the def nitive treatment in severe cases. First-degree AV block Can occur in normal individuals; associated with ↑ vagal tone and with β-blocker or CCB use. Asymptomatic. PR interval > 200 msec. None necessary. Second-degree AV block (Mobitz I/ Wenckebach) Drug effects (digoxin, β-blockers, CCBs) or ↑ vagal tone; sinoatrial conduction disease; right coronary ischemia or infarction. Usually asymptomatic. Progressive PR lengthening until a dropped beat occurs; PR interval then resets. Stop the offending drug. Atropine or pacemaker placement as clinically indicated.


First_Aid_Step2

First_Aid_Step2. or infarction. Usually asymptomatic. Progressive PR lengthening until a dropped beat occurs; PR interval then resets. Stop the offending drug. Atropine or pacemaker placement as clinically indicated. Second-degree AV block (Mobitz II) Results from f brotic disease of the conduction system or from acute, subacute, or prior myocardial infarction (MI). Occasionally syncope; frequent progression to third-degree AV block. Unexpected dropped beat(s) without a change in PR interval. Pacemaker placement. Third-degree AV block (complete) No electrical communication between the atria and ventricles. Syncope, dizziness, acute heart failure, hypotension, cannon A waves. No relationship between P waves and QRS complexes. Pacemaker placement. Sick sinus syndrome (SSS)/ tachycardia-bradycardia syndrome A heterogeneous disorder consisting of abnormalities in supraventricular impulse generation and conduction that lead to intermittent supraventricular tachy-and bradyarrhythmias. 2° to tachycardia or


First_Aid_Step2

First_Aid_Step2. A heterogeneous disorder consisting of abnormalities in supraventricular impulse generation and conduction that lead to intermittent supraventricular tachy-and bradyarrhythmias. 2° to tachycardia or bradycardia; may include syncope, palpitations, dyspnea, chest pain, TIA, and stroke. The most common indication for pacemaker placement.


First_Aid_Step2

First_Aid_Step2. T AB LE 2.1 -2. Supraventricular Tachyarrhythmias Atrial Sinus tachycardia Normal physiologic response to fear, pain, and exercise. Can also be 2° to hyperthyroidism, volume contraction, infection, or pulmonary embolism. Palpitations, shortness of breath. Ventricular rate > 100 bpm; normal P waves before every QRS complex. Treat the underlying cause. Atrial f brillation (AF) Acute AF— PIRATES: Pulmonary disease Ischemia Rheumatic heart disease Anemia/Atrial myxoma Thyrotoxicosis Ethanol Sepsis Chronic AF— hypertension, CHF. Often asymptomatic, but may present with shortness of breath, chest pain, or palpitations. Physical exam reveals irregularly irregular pulse. No discernible P waves, with variable and irregular QRS response. Estimate risk of stroke using CHAD2 score. Anticoagulation if > 48 hours (to prevent CVA); rate control (CCBs, β-blockers, digoxin, amiodarone).


First_Aid_Step2

First_Aid_Step2. Estimate risk of stroke using CHAD2 score. Anticoagulation if > 48 hours (to prevent CVA); rate control (CCBs, β-blockers, digoxin, amiodarone). Initiate cardioversion only if new onset (< 48 hours) or if transesophageal echocardiogram (TEE) shows no left atrial clot, or after 3–6 weeks of warfarin treatment with satisfactory INR (2–3). See the Hematology chapter for more information on warfarin. T AB LE 2.1 -2. Supraventricular Tachyarrhythmias (continued) Atrioventricular Circular movement Palpitations, shortness of breath, angina, A retrograde P Same as that for reciprocating of an impulse syncope, lightheadedness. wave is often AVNRT. tachycardia between the AV


First_Aid_Step2

First_Aid_Step2. Atrial f utter Circular movement of electrical activity around the atrium at a rate of 300 times per minute. Usually asymptomatic, but can present with palpitations, syncope, and lightheadedness. Regular rhythm; “sawtooth” appearance of P waves can be seen. Atrial rate is usually 240–320 bpm with varying degrees of blockade. Anticoagulation and rate control. Cardiovert according to AF criteria. Multifocal atrial tachycardia Multiple atrial pacemakers or reentrant pathways; COPD, hypoxemia. May be asymptomatic. Three or more unique P-wave Treat the underlying morphologies; or β-blockers for rate > 100 bpm. rate control and disorder; verapamil suppression of atrial pacemakers (not very effective). AV junction reentry tachycardia depolarizes Atrioventricular A reentry circuit Palpitations, shortness of breath, angina, Rate 150–250 Carotid massage, nodal (AVNRT) in the AV node the atrium and ventricle nearly simultaneously. syncope, lightheadedness. bpm; P wave is often buried Valsalva,


First_Aid_Step2

First_Aid_Step2. shortness of breath, angina, Rate 150–250 Carotid massage, nodal (AVNRT) in the AV node the atrium and ventricle nearly simultaneously. syncope, lightheadedness. bpm; P wave is often buried Valsalva, or adenosine in QRS or shortly after. arrhythmia. Cardiovert can stop the if hemodynamically unstable.


First_Aid_Step2

First_Aid_Step2. seen after a (AVRT) node and the normal QRS. atrium through a bypass tract. Seen in Wolff-Parkinson-White syndrome. Paroxysmal atrial tachycardia Rapid ectopic pacemaker in the atrium (not sinus node). Palpitations, shortness of breath, angina, syncope, lightheadedness. Rate > 100 bpm; P wave with an unusual axis before each normal QRS. Adenosine can be used to unmask underlying atrial activity. T AB LE 2.1 -3. Ventricular Tachyarrhythmias


First_Aid_Step2

First_Aid_Step2. Premature ventricular contraction (PVC) Ectopic beats arise from ventricular foci. Associated with hypoxia, electrolyte abnormalities, and hyperthyroidism. Usually asymptomatic, but may lead to palpitations. Early, wide QRS not preceded by a P wave. PVCs are usually followed by a compensatory pause. Treat the underlying cause. If symptomatic, give β-blockers or occasionally other antiarrhythmics. Ventricular tachycardia (VT) Can be associated with CAD, MI, and structural heart disease. Nonsustained VT is often asymptomatic; sustained ventricular tachycardia can lead to palpitations, hypotension, angina, and syncope. Can progress to VF. Three or more consecutive PVCs; wide QRS complexes in a regular rapid rhythm; AV dissociation. Cardioversion and antiarrhythmics (e.g., amiodarone, lidocaine, procainamide). Ventricular f brillation (VF) Associated with CAD and structural heart disease. Also associated with cardiac arrest (together with asystole). Syncope, absence of blood pressure,


First_Aid_Step2

First_Aid_Step2. procainamide). Ventricular f brillation (VF) Associated with CAD and structural heart disease. Also associated with cardiac arrest (together with asystole). Syncope, absence of blood pressure, pulselessness. Totally erratic wide-complex tracing. Immediate electrical cardioversion and ACLS protocol. Torsades de pointes Associated with long QT syndrome, proarrhythmic response to medications, hypokalemia, and congenital deafness. Can present with sudden cardiac death; typically associated with palpitations, dizziness, and syncope. Polymorphous QRS; VT with rates between 150 and 250 bpm. Correct hypokalemia; withdraw offending drugs. Give magnesium initially and cardiovert if unstable.


First_Aid_Step2

First_Aid_Step2. T AB LE 2.1 -4. AHA/ACC Classifcation and Treatment of CHF A B Patients with structural heart disease (e.g., a history of MI, left ventricular systolic dysfunction, or valvular disease) who have never had symptoms of CHF. ACEIs, β-blockers. Patients with structural heart disease who have prior or current symptoms of CHF (shortness of breath, fatigue, ↓ exercise tolerance). Treatment includes diuretics, ACEIs, β-blockers, digitalis, and dietary salt restriction. Patients with marked symptoms of CHF at rest despite maximal medical therapy. C D Patients who are at high risk of developing CHF because of the presence of risk factors, but who have no identifed structural or functional abnormalities and no signs or symptoms of CHF. Manage treatable risk factors (hypertension, smoking, hyperlipidemia, obesity, exercise, alcohol abuse). ACEIs can be used in patients with atherosclerotic vascular disease, DM, or hypertension.


First_Aid_Step2

First_Aid_Step2. Manage treatable risk factors (hypertension, smoking, hyperlipidemia, obesity, exercise, alcohol abuse). ACEIs can be used in patients with atherosclerotic vascular disease, DM, or hypertension. Treatment options include mechanical assist devices, heart transplantation, continuous IV inotropic drugs, and hospice care for end-stage patients. T AB LE 2.1 -5. NYHA Functional Classifcation of CHF T AB LE 2.1 -6. Left-Sided vs. Right-Sided Heart Failure TAB LE 2.1 -7. Comparison of Systolic and Diastolic Dysfunction Patient age Often < 65 years of age. Often > 65 years of age. Comorbidities Dilated cardiomyopathy, valvular heart disease. Restrictive or hypertrophic cardiomyopathy; renal disease or hypertension. Physical exam Displaced PMI, S3 gallop. Sustained PMI, S4 gallop. CXR Pulmonary congestion, cardiomegaly. Pulmonary congestion, normal heart size. ECG/echocardiography Q waves, ↓ EF (< 40%). LVH, normal EF (> 55%).


First_Aid_Step2

First_Aid_Step2. The most common cause of right-sided heart failure is left-sided heart failure. Diuretics are for symptomatic relief only and confer no mortality benef t. Heart failure caused by systolic dysfunction is defined as a ↓ EF (< 50%) and left ventricular end-diastolic volumes. It is caused by inadequate left ventricular contractility or ↑ afterload. The heart compensates for low EF and preload through hypertrophy and ventricular dilation (Frank-Starling law), but the compensation ultimately fails, leading to ↑ myocardial work and worsening systolic function. Exertional dyspnea is the earliest and most common presenting symptom and progresses to orthopnea, paroxysmal nocturnal dyspnea (PND), and finally rest dyspnea. Chronic cough, fatigue, lower extremity edema, nocturia, Cheyne-Stokes respirations, and/or abdominal fullness may be seen. Look for signs to distinguish leftfrom right-sided heart failure (see Table 2.1-6).


First_Aid_Step2

First_Aid_Step2. Look for signs to distinguish leftfrom right-sided heart failure (see Table 2.1-6). CHF is a clinical syndrome whose diagnosis is based on signs and symptoms. Exam reveals parasternal lift, an elevated and sustained left ventricular impulse, and an S3/S4 gallop. CXR: Cardiomegaly, cephalization of pulmonary vessels, pleural effusions, vascular plumpness, and prominent hila. Echocardiogram: ↓ EF and ventricular dilation. Lab abnormalities: BNP > 500, ↑ creatinine, ↓ sodium. ECG: Usually nondiagnostic, but MI or AF may precipitate acute exacerbations. ■Acute: Correct underlying causes such as arrhythmias, myocardial ischemia, and drugs (e.g., CCBs, antiarrhythmics, NSAIDs, alcohol, thyroid and valvular disease, high-output states). Diurese aggressively with loop and thiazide diuretics (see Table 2.1-8). TABLE 2.1-8. Types of Diuretics


First_Aid_Step2

First_Aid_Step2. Loop diuretics Furosemide, ethacrynic acid, bumetanide, torsemide Loop of Henle ↓ Na+/K+/2Cl− cotransporter; ↓ urine concentration; ↑ Ca2+ excretion. Ototoxicity, hypokalemia, hypocalcemia, dehydration, gout. Thiazide diuretics HCTZ, chlorothiazide, chlorthalidone Early distal tubule ↓ NaCl reabsorption leading to ↓ diluting capacity of nephron; ↓ Ca2+ excretion. Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia. K+-sparing agents Spironolactone, triamterene, amiloride Cortical collecting tubule Spironolactone is an aldosterone receptor antagonist; triamterene and amiloride block Na+ channels. Hyperkalemia, gynecomastia, hirsutism, sexual dysfunction. Carbonic anhydrase inhibitors Acetazolamide Proximal convoluted tubule NaHCO3 diuresis ↓ total body NaHCO3. Hyperchloremic metabolic acidosis, neuropathy, NH3 toxicity, sulfa allergy. Osmotic agents Mannitol Proximal tubule Creates ↑ tubular f uid osmolarity, leading to ↑ urine f


First_Aid_Step2

First_Aid_Step2. ↓ total body NaHCO3. Hyperchloremic metabolic acidosis, neuropathy, NH3 toxicity, sulfa allergy. Osmotic agents Mannitol Proximal tubule Creates ↑ tubular f uid osmolarity, leading to ↑ urine f ow. Pulmonary edema, dehydration. Contraindicated in anuria and CHF.


First_Aid_Step2

First_Aid_Step2. Give ACEIs to all patients who can tolerate them. If a patient cannot tolerate ACEIs, consider an angiotensin receptor blocker (ARB). β-blockers should not be used during decompensated CHF but should be started once the patient is euvolemic. Treat acute pulmonary congestion with LMNOP (see mnemonic). Chronic: Control comorbid conditions (e.g., diabetes, hypertension, obesity) and limit dietary sodium and ﬂ uid intake. Long-term β-blockers and ACEIs/ARBs together help prevent neurohormonal remodeling of the heart. All of these agents ↓ mortality for New York Heart Association (NYHA) class II–IV patients. Daily ASA and a statin are recommended for ischemic heart disease to prevent further ischemic events. Chronic diuretic therapy (loop diuretics +/– thiazide) can prevent volume overload.


First_Aid_Step2

First_Aid_Step2. Daily ASA and a statin are recommended for ischemic heart disease to prevent further ischemic events. Chronic diuretic therapy (loop diuretics +/– thiazide) can prevent volume overload. Low-dose spironolactone ↓ mortality risk when given with ACEIs and loop diuretics in patients with left ventricular systolic dysfunction and NYHA class III–IV heart failure. Monitor for hyperkalemia. Anticoagulate patients with AF and those with a history of previous embolic events or a mobile left ventricular thrombus. Consider an implantable biventricular cardiac defibrillator (ICD) in patients with both an EF < 30% and CAD. Loops lose calcium, whereas thiazides save it. ■CHF that is unresponsive to maximal medical therapy may require a mechanical left ventricular assist device or cardiac transplantation.


First_Aid_Step2

First_Aid_Step2. Loops lose calcium, whereas thiazides save it. ■CHF that is unresponsive to maximal medical therapy may require a mechanical left ventricular assist device or cardiac transplantation. Defined by ↓ ventricular compliance with normal systolic function. The ventricle has either impaired active relaxation (2° to ischemia, aging, and/or hypertrophy) or impaired passive filling (scarring from prior MI; restrictive cardiomyopathy). Left ventricular end-diastolic pressure ↑, cardiac output remains essentially normal, and EF is normal or ↑. Associated with stable and unstable angina, shortness of breath, dyspnea on exertion, arrhythmias, MI, heart failure, and sudden death. Diuretics are first-line therapy (see Table 2.1-8). Maintain rate and BP control via β-blockers, ACEIs, ARBs, or CCBs. Digoxin is not useful in these patients. Myocardial disease; categorized as dilated, hypertrophic, or restrictive (see Table 2.1-9).


First_Aid_Step2

First_Aid_Step2. Digoxin is not useful in these patients. Myocardial disease; categorized as dilated, hypertrophic, or restrictive (see Table 2.1-9). The most common cardiomyopathy. Left ventricular dilation and systolic dysfunction (low EF) must be present for diagnosis. Most cases are idiopathic, but known 2° causes include alcohol, myocarditis, postpartum status, drugs (doxorubicin, AZT, cocaine), endocrinopathies (thyroid dysfunction, acromegaly, pheochromocytoma), infection (coxsackievirus, HIV, Chagas’ disease, parasites), genetic factors, and nutritional disorders (wet beriberi). The two most common causes of 2° dilated cardiomyopathy are ischemia and long-standing hypertension. T AB LE 2.1 -9. Differential Diagnosis of Cardiomyopathies


First_Aid_Step2

First_Aid_Step2. T AB LE 2.1 -9. Differential Diagnosis of Cardiomyopathies Major abnormality Impaired contractility Impaired relaxation Impaired elasticity Left ventricular cavity size (end diastole) ↑↑ ↓ ↑ Left ventricular cavity size (end systole) ↑↑ ↓↓ ↑ Ejection fraction (EF) ↓↓ ↑ or ↔ ↓ or ↔ Wall thickness ↓, variable ↑↑ ↑, variable Often presents with gradual development of CHF symptoms. Exam often reveals displacement of the left venticular impulse, JVD, an S3/S4 gallop, or mitral/tricuspid regurgitation. Echocardiography is diagnostic. ECG may show nonspecific ST-T changes, low-voltage QRS, sinus tachycardia, and ectopy. LBBB is common. CXR shows an enlarged, balloon-like heart and pulmonary congestion. Address the underlying etiology (e.g., stop all alcohol use, treat endocrine disorders).


First_Aid_Step2

First_Aid_Step2. CXR shows an enlarged, balloon-like heart and pulmonary congestion. Address the underlying etiology (e.g., stop all alcohol use, treat endocrine disorders). Treat symptoms of CHF with diuretics, and prevent disease progression with ACEIs, β-blockers, and aldosterone antagonists. Consider anticoagulation to ↓ thrombus risk only if AF or an intraventricular thrombus is present. Digoxin is a second-line agent; avoid CCBs in CHF. Consider an ICD if EF < 35%.


First_Aid_Step2

First_Aid_Step2. Consider an ICD if EF < 35%. LVH results in impaired left ventricular relaxation and filling (diastolic dysfunction). Hypertrophy frequently involves the interventricular septum, leading to left ventricular outﬂow tract obstruction and impaired ejection of blood. The congenital form, hypertrophic obstructive cardiomyopathy (HOCM), is inherited as an autosomal-dominant trait in 50% of HOCM patients and is the most common cause of sudden death in young, healthy athletes in the United States. Other causes of marked hypertrophy include hypertension and aortic stenosis. Patients may be asymptomatic but may also present with syncope, dyspnea, palpitations, angina, or sudden cardiac death. Exam often reveals a sustained apical impulse, an S4 gallop, and a systolic ejection crescendo-decrescendo murmur that ↑ with ↓ preload (e.g., Valsalva maneuver, squatting).


First_Aid_Step2

First_Aid_Step2. Exam often reveals a sustained apical impulse, an S4 gallop, and a systolic ejection crescendo-decrescendo murmur that ↑ with ↓ preload (e.g., Valsalva maneuver, squatting). Obstruction is worsened by ↑ myocardial contractility or by ↓ left ventricular filling (e.g., exercise, Valsalva maneuvers, vasodilators, dehydration). Echocardiography is diagnostic and shows an asymmetrically thickened left ventricular wall and dynamic obstruction of blood ﬂ ow. ECG may show signs of LVH. CXR may reveal left atrial enlargement (LAE) 2° to mitral regurgitation. ■β-blockers are initial therapy for symptomatic relief; CCBs are second-line agents. An S3 gallop signif es the end of rapid ventricular f lling in the setting of f uid overload and is associated with dilated cardiomyopathy. Hypertrophic cardiomyopathy is the most common cause of sudden death in young, healthy athletes in the United States.


First_Aid_Step2

First_Aid_Step2. Hypertrophic cardiomyopathy is the most common cause of sudden death in young, healthy athletes in the United States. An S4 gallop signif es a stiff, noncompliant ventricle and associated with hypertrophic cardiomyopathy. Surgical options for HOCM include dual-chamber pacing, partial excision or catheter ablation of the myocardial septum, ICD placement, and mitral valve replacement. Patients should avoid intense athletic competition and training. Defined as ↓ elasticity of myocardium leading to impaired diastolic filling without significant systolic dysfunction (a normal or near-normal EF). It is caused by infiltrative disease (amyloidosis, sarcoidosis, hemochromatosis) or by scarring and fibrosis (2° to radiation or doxorubicin). Signs and symptoms of left-sided and right-sided heart failure occur, but symptoms of right-sided heart failure (JVD, peripheral edema) often predominate.


First_Aid_Step2

First_Aid_Step2. Signs and symptoms of left-sided and right-sided heart failure occur, but symptoms of right-sided heart failure (JVD, peripheral edema) often predominate. CXR, MRI, and cardiac catheterization may be helpful, but echocardiography is key to diagnosis and reveals rapid early filling with a normal or near-normal EF. Cardiac biopsy may reveal fibrosis or evidence of infiltration. ECG frequently shows LBBB. Therapeutic options are limited and generally are palliative only. Medical treatment includes cautious use of diuretics for ﬂuid overload, vasodilators to ↓ filling pressure, and anticoagulation if not contraindicated. Major risk factors for CAD include age, male gender, hyperlipidemia, DM, hypertension, obesity, a family history, and smoking. The classic triad of angina consists of substernal chest pain that is provoked by exertion and relieved by rest or nitrates.


First_Aid_Step2

First_Aid_Step2. The classic triad of angina consists of substernal chest pain that is provoked by exertion and relieved by rest or nitrates. Clinical manifestations of CAD include stable and unstable angina, shortness of breath, dyspnea on exertion, arrhythmias, MI, heart failure, and sudden death. Risk factors include DM, a family history of premature CAD, smoking, dyslipidemia, abdominal obesity, hypertension, and male gender. Substernal chest pain 2° to myocardial ischemia (O2 supply and demand mismatch). Prinzmetal’s (variant) angina mimics angina pectoris but is caused by vasospasm of coronary vessels. It classically affects young women at rest in the early morning and is associated with ST-segment elevation in the absence of cardiac enzyme elevation. The classic triad consists of substernal chest pain or pressure (often described as a heaviness or pressure without pain), usually precipitated by stress or exertion and relieved by rest or nitrates.


First_Aid_Step2

First_Aid_Step2. Pain can radiate to the left arm, jaw, and neck and may be associated with shortness of breath, nausea/vomiting, diaphoresis, or lightheadedness. Examination of patients experiencing stable angina is generally unremarkable. Look for carotid and peripheral bruits suggesting atherosclerosis and hypertension. Rule out pulmonary, GI, or other cardiac causes of chest pain. Angina may be diagnosed from the history alone, but significant ST-segment changes on exercise stress test with ECG monitoring is diagnostic of CAD. Women and diabetics classically experience “silent” ischemic events and present “atypically”; for this reason, it is necessary to maintain a high index of suspicion in this patient population. Treat acute symptoms with ASA, O2 and/or IV nitroglycerin, and IV morphine, and consider IV β-blockers. The efficacy of nondihydropyridine CCBs (diltiazem, verapamil) and ACEIs has also been validated.


First_Aid_Step2

First_Aid_Step2. Patients with a suspected MI must be admitted and monitored until acute MI is ruled out by serial cardiac enzymes. Treat chronic symptoms with nitrates, ASA, and β-blockers; CCBs are second-line agents for symptomatic control only. Initiate risk factor reduction (e.g., smoking, cholesterol, hypertension). Hormone replacement therapy is not protective in postmenopausal women. Women, diabetics, the elderly, and post–heart transplant patients may have atypical, clinically silent MIs. Only ASA and β-blockers have been shown to have a mortality benef t in the treatment of angina. A spectrum of clinical syndromes caused by plaque disruption or vasospasm that leads to acute myocardial ischemia.


First_Aid_Step2

First_Aid_Step2. A spectrum of clinical syndromes caused by plaque disruption or vasospasm that leads to acute myocardial ischemia. Unstable angina describes chest pain that is new onset, is accelerating (i.e., occurs with less exertion, lasts longer, or is less responsive to medications), or occurs at rest; it is distinguished from stable angina by patient history. It signals the presence of possible impending infarction based upon plaque instability. In contrast, NSTEMI indicates myocardial necrosis marked by elevations in troponin I, troponin T, or CK-MB. Patients should be risk stratified according to the TIMI (Thrombolysis in Myocardial Infarction study) criteria to determine the likelihood of adverse cardiac events (see Table 2.1-10). Unstable angina is not associated with elevated cardiac markers, but ST changes may be seen on ECG and are indicative of high-risk occlusions. NSTEMI is diagnosed by serial cardiac enzymes and ECG.


First_Aid_Step2

First_Aid_Step2. Unstable angina is not associated with elevated cardiac markers, but ST changes may be seen on ECG and are indicative of high-risk occlusions. NSTEMI is diagnosed by serial cardiac enzymes and ECG. Acute treatment of symptoms is the same as that for stable angina. Clopidogrel, unfractionated heparin or enoxaparin, and glycoprotein IIb/IIIa inhibitors (e.g., eptifibatide, tirofiban, abciximab) should also be considered. Patients with chest pain refractory to medical therapy, a TIMI score of ≥ 3, a troponin elevation, or ST changes > 1 mm should be given heparin and scheduled for angiography and possible revascularization (percutaneous coronary intervention [PCI] or CABG). Think unstable angina if chest pain is new onset, accelerating, or occurring at rest. T AB LE 2.1 -1 0. TIMI Risk Score for Unstable Angina/NSTEMI DEATH, MI, OR URGENT CHARACTERISTICS POINT RISK SCORE DEATH OR MI REVASCULARIZATION


First_Aid_Step2

First_Aid_Step2. T AB LE 2.1 -1 0. TIMI Risk Score for Unstable Angina/NSTEMI DEATH, MI, OR URGENT CHARACTERISTICS POINT RISK SCORE DEATH OR MI REVASCULARIZATION History Age ≥ 65 years 1 0/1 3 5 ≥ 3 CAD risk factors (family history, DM, tobacco, hypertension, ↑ cholesterol) 1 2 3 8 Known CAD (stenosis > 50%) 1 3 5 13 ASA use in past seven days 1 4 7 20 Presentation 5 12 26 Severe angina (≥ 2 episodes within 24 hours) 1 6/7 19 41 ST deviation ≥ 0.5 mm 1 + cardiac marker 1 Risk score—total points (0–7) Higher-risk patients (risk score ≥ 3) beneft more from enoxaparin (vs. unfractionated heparin), glycoprotein IIb/IIIa inhibitors, and early angiography. Defined as ST-segment elevations and cardiac enzyme release 2° to prolonged cardiac ischemia and necrosis. Presents with acute-onset substernal chest pain, commonly described as a pressure or tightness that can radiate to the left arm, neck, or jaw.


First_Aid_Step2

First_Aid_Step2. Presents with acute-onset substernal chest pain, commonly described as a pressure or tightness that can radiate to the left arm, neck, or jaw. Associated symptoms may include diaphoresis, shortness of breath, lightheadedness, anxiety, nausea/vomiting, and syncope. Physical exam may reveal arrhythmias, new mitral regurgitation (ruptured papillary muscle), hypotension (cardiogenic shock), and evidence of new CHF (rales, peripheral edema, S3 gallop). The best predictor of survival is left ventricular EF. ■ECG: Look for ST-segment elevations or new LBBB. ST-segment depressions in leads V1–V2 can also be reciprocal change indicating infarction in the posterior wall. Sequence of ECG changes: Peaked T waves → ST-segment elevation → Q waves → T-wave inversion → ST-segment normalization → T-wave normalization over several hours to days.


First_Aid_Step2

First_Aid_Step2. Sequence of ECG changes: Peaked T waves → ST-segment elevation → Q waves → T-wave inversion → ST-segment normalization → T-wave normalization over several hours to days. Cardiac enzymes: Troponin I is most sensitive; CK-MB is more specific. Both can take up to six hours to rise after the onset of chest pain (see Figure 2.1-4). ST-segment abnormalities: ST-segment elevation in leads II, III, and aVF is consistent with an inferior MI involving the RCA/PDA and LCA (see Figure 2.1-5). ST-segment elevation in leads V1–V4 usually indicates an anterior MI involving the LAD and diagonal branches (see Figure 2.1-6). ST-segment elevation in leads I, aVL, and V5–V6 points to a lateral MI involving the LCA. ST-segment depression in leads V1–V2 can be “reciprocal change” indicative of an acute infarct in the posterior wall. Six key medications should be considered: ASA, β-blockers, clopidogrel, morphine, nitrates, and O2.


First_Aid_Step2

First_Aid_Step2. Six key medications should be considered: ASA, β-blockers, clopidogrel, morphine, nitrates, and O2. If the patient is in heart failure or in cardiogenic shock, do not give β-blockers; instead, give ACEIs, provided that the patient is not hypotensive. Emergent angiography and PCI should be performed; if possible, the patient should undergo PCI for the lesion thought to be responsible for STEMI. Common causes of chest pain include GERD, angina, esophageal pain, musculoskeletal disorders (costochondritis, trauma), and pneumonia. Other causes of ST-segment elevation (often diffuse across multiple leads) include acute pericarditis, LVH, LBBB, and a normal variant (e.g., “early repolarization”). F IGU R E 2.1 -4. Typical pattern of serum marker elevation after an acute MI.


First_Aid_Step2

First_Aid_Step2. F IGU R E 2.1 -4. Typical pattern of serum marker elevation after an acute MI. CK-MB = creatine kinase, MB isoenzyme; cTnI = cardiac troponin I; cTnT = cardiac troponin T; LD1 = lactate dehydrogenase isoenzyme 1; MLC = myosin light chain. (Reproduced, with permission, from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004: Fig. 49-1.) FIGURE 2.1-5. Inferior wall MI. In this patient with acute chest pain, the ECG demonstrated acute ST-segment elevation in leads II, III, and aVF with reciprocal ST-segment depression and T-wave ﬂattening in leads I, aVL, and V4–V6. (Reproduced, with permission, from Stobo J et al. The Principles and Practice of Medicine, 23rd ed. Stamford, CT: Appleton & Lange, 1996: 20.) FIGURE 2.1-6. Anterior wall MI.


First_Aid_Step2

First_Aid_Step2. FIGURE 2.1-6. Anterior wall MI. This patient presented with acute chest pain. The ECG showed acute ST-segment elevation in leads aVL and V1–V6, and hyperacute T waves. (Reproduced, with permission, from Stobo J et al. The Principles and Practice of Medicine, 23rd ed. Stamford, CT: Appleton & Lange, 1996: 19.) If the patient presents within three hours, PCI cannot be performed within 90 minutes, and there are no contraindications to thrombolysis (e.g., a history of hemorrhagic stroke or recent ischemic stroke, severe heart failure, or cardiogenic shock), thrombolysis with tPA, reteplase, or streptokinase should be performed instead of PCI. In the setting of three-vessel disease, left main coronary artery disease, discrete lesions not amenable to PCI, or diffuse disease with good target vessels, PCI should be attempted immediately for the lesion thought to be responsible for STEMI; the patient is a candidate for CABG afterward.


First_Aid_Step2

First_Aid_Step2. Long-term treatment includes ASA, ACEIs, β-blockers, high-dose statins, and clopidogrel (if PCI was performed). Modify risk factors with dietary changes, exercise, and tobacco cessation. Arrhythmia is the most common complication and cause of death following acute MI; lethal arrhythmia is the most common cause of death following acute MI. Less common complications include reinfarction, left ventricular wall rupture, VSD, pericarditis, papillary muscle rupture (with mitral regurgitation), left ventricular aneurysm or pseudoaneurysm, and mural thrombi. Dressler’s syndrome, an autoimmune process occurring 2–10 weeks post-MI, presents with fever, pericarditis, pleural effusion, leukocytosis, and ↑ ESR. A timeline of common post-MI complications is as follows: First day: Heart failure (treat with nitroglycerin and diuretics). 2–4 days: Arrhythmia, pericarditis (diffuse ST elevation with PR depression).


First_Aid_Step2

First_Aid_Step2. First day: Heart failure (treat with nitroglycerin and diuretics). 2–4 days: Arrhythmia, pericarditis (diffuse ST elevation with PR depression). 5–10 days: Left ventricular wall rupture (acute pericardial tamponade causing electrical alternans, pulseless electrical activity), papillary muscle rupture (severe mitral regurgitation). Weeks to months: Ventricular aneurysm (CHF, arrhythmia, persistent ST elevation, mitral regurgitation, thrombus formation). Unable to perform PCI (diffuse disease) Stenosis of left main coronary artery Triple-vessel disease Total cholesterol > 200 mg/dL, LDL > 130 mg/dL, triglycerides > 500 mg/ dL, and HDL < 40 mg/dL are risk factors for CAD. Etiologies include obesity, DM, alcoholism, hypothyroidism, nephrotic syndrome, hepatic disease, Cushing’s disease, OCP use, high-dose diuretic use, and familial hypercholesterolemia. Most patients have no specific signs or symptoms.


First_Aid_Step2

First_Aid_Step2. Most patients have no specific signs or symptoms. Patients with extremely high triglyceride or LDL levels may have xanthomas (eruptive nodules in the skin over the tendons), xanthelasmas (yellow fatty deposits in the skin around the eyes), and lipemia retinalis (creamy appearance of retinal vessels). Dyslipidemia: ■Conduct a fasting lipid profile for patients > 20 years of age and repeat ev ery five years or sooner if elevated. ■Total serum cholesterol > 200 mg/dL on two different occasions is diagnostic of hypercholesterolemia. T AB LE 2.1 -1 1. ATP III Guidelines for Risk Stratifcation of Hypercholesterolemia


First_Aid_Step2

First_Aid_Step2. ■Total serum cholesterol > 200 mg/dL on two different occasions is diagnostic of hypercholesterolemia. T AB LE 2.1 -1 1. ATP III Guidelines for Risk Stratifcation of Hypercholesterolemia CAD or CAD risk equivalentsa < 100 mg/dL (or < 70) > 100 mg/dL > 130 mg/dL 2+ risk factorsb < 130 mg/dL > 130 mg/dL > 160 mg/dL 0–1 risk factorb < 160 mg/dL > 160 mg/dL > 190 mg/dL a CAD risk equivalents = symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes. b Risk factors = cigarette smoking, hypertension, low HDL (< 40 mg/dL), a family history of premature CAD, and age (men > 45 years; women > 55 years). An HDL > 60 mg/dL counts as a “negative” risk factor and removes one risk factor from the total score. ■LDL > 130 mg/dL or HDL < 40 mg/dL, even if total serum cholesterol is < 200 mg/dL, is diagnostic of dyslipidemia.


First_Aid_Step2

First_Aid_Step2. ■LDL > 130 mg/dL or HDL < 40 mg/dL, even if total serum cholesterol is < 200 mg/dL, is diagnostic of dyslipidemia. Based on risk stratification (see Table 2.1-11). Risk factors include diabetes (considered a CAD risk equivalent), smoking, hypertension, HDL < 40 mg/dL, age > 45 (males), age > 55 (females), and early CAD in first-degree relatives (males < 55 and females < 65). The first intervention should be a 12-week trial of diet and exercise in a patient with no known atherosclerotic vascular disease. Commonly used lipid-lowering agents are listed in Table 2.1-12. The BP goal in uncomplicated hypertension is < 140/< 90. For diabetics or patients with renal disease, the goal is < 130/< 80. Defined as a systolic BP > 140 mmHg and/or a diastolic BP > 90 based on three measurements separated in time (see Table 2.1-13). Classified as 1° or 2°.


First_Aid_Step2

First_Aid_Step2. Defined as a systolic BP > 140 mmHg and/or a diastolic BP > 90 based on three measurements separated in time (see Table 2.1-13). Classified as 1° or 2°. Hypertension with no identifiable cause. Represents 95% of cases of hypertension. Risk factors include a family history of hypertension or heart disease, a high-sodium diet, smoking, obesity, race (blacks > whites), and advanced age. Hypertension is asymptomatic until complications develop. Patients should be evaluated for end-organ damage to the brain (stroke, dementia), eye (cotton-wool exudates, hemorrhage), heart (LVH), and kidney (proteinuria, chronic kidney disease). Renal bruits may signify renal artery stenosis as the cause of hypertension. Conduct cardiovascular, neurologic, ophthalmologic, and abdominal exams. Obtain a UA, BUN/creatinine, CBC, and electrolytes to assess the extent of end-organ damage. T AB LE 2.1 -1 2. Lipid-Lowering Agents


First_Aid_Step2

First_Aid_Step2. HMG-CoA reductase inhibitors (statins) Atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin Inhibit the rate-limiting step in cholesterol synthesis. ↓ LDL, ↓ triglycerides ↑ LFTs, myositis, warfarin potentiation. Lipoprotein lipase stimulators (f brates) Gemf brozil ↑ lipoprotein lipase, leading to ↑ VLDL and triglyceride catabolism. ↓ triglycerides, ↑ HDL GI upset, cholelithiasis, myositis, ↑ LFTs. Cholesterol absorption inhibitors Ezetimibe (Zetia) ↓ absorption of cholesterol at the small intestine brush border. ↓ LDL Diarrhea, abdominal pain. Can cause angioedema. Niacin Niaspan ↓ fatty acid release from adipose tissue; ↓ hepatic synthesis of LDL. ↑ HDL, ↓ LDL Skin fushing (can be prevented with ASA), paresthesias, pruritus, GI upset, ↑ LFTs. Bile acid resins Cholestyramine, colestipol, colesevelam Bind intestinal bile acids lead to ↓ bile acid stores and ↑ catabolism of LDL from plasma. ↓ LDL Constipation, GI upset, LFT abnormalities, myalgias. Can ↓ absorption of


First_Aid_Step2

First_Aid_Step2. colestipol, colesevelam Bind intestinal bile acids lead to ↓ bile acid stores and ↑ catabolism of LDL from plasma. ↓ LDL Constipation, GI upset, LFT abnormalities, myalgias. Can ↓ absorption of other drugs from the small intestine.


First_Aid_Step2

First_Aid_Step2. T AB LE 2.1 -1 3. JNC-7 Classifcation and Management of Hypertension Normal < 120 and < 80 Encourage Prehypertension 120–139 or 80–89 Yes No antihypertensive drug indicated. Stage 1 hypertension 140–159 or 90–99 Yes Thiazide diuretics for most patients; ACEIs, ARBs, β-blockers, CCBs, or a combination may be considered. Stage 2 hypertension ≥ 160 or ≥ 100 Yes Two-drug combination for most patients (usually a thiazide diuretic plus an ACEI, an ARB, a β-blocker, or a CCB). Hypertensive crises are diagnosed on the basis of the extent of end-organ damage, not BP measurement. Rule out 2° causes of hypertension, particularly in younger patients. Begin with lifestyle modifications (e.g., weight loss, smoking cessation, salt reduction). Weight loss is the single most effective lifestyle modification. The BP goal in otherwise healthy patients is < 140/< 90. The goal in diabetics or patients with renal disease with proteinuria is < 130/< 80.


First_Aid_Step2

First_Aid_Step2. Diuretics (which are inexpensive and particularly effective in African-Americans), ACEIs, and β-blockers (which are beneficial for patients with CAD) have been shown to ↓ mortality in uncomplicated hypertension. They are first-line agents unless a comorbid condition requires another medication (see Table 2.1-14). Periodically test for end-organ complications, including renal (BUN, creatinine, urine protein-to-creatinine ratio) and cardiac (ECG evidence of hypertrophy) complications. Hypertension 2° to an identifiable organic cause. See Table 2.1-15 for the diagnosis and treatment of common causes. A spectrum of clinical presentations in which elevated BPs lead to end-organ damage. Presents with end-organ damage revealed by chest pain (ischemia or MI), back pain (aortic dissection), or changes in mental status (hypertensive encephalopathy).


First_Aid_Step2

First_Aid_Step2. Presents with end-organ damage revealed by chest pain (ischemia or MI), back pain (aortic dissection), or changes in mental status (hypertensive encephalopathy). Hypertensive urgency: Diagnosed on the basis of an elevated BP with only mild to moderate symptoms (headache, chest pain, syncope) and without end-organ damage. Hypertensive emergency: Diagnosed by a significantly elevated BP with signs or symptoms of impending end-organ damage such as ARF, intracra- T AB LE 2.1 -1 4. Treatment of 1° Hypertension with Comorbid Conditions Heart failure Thiazide diuretics, β-blockers, ACEIs, ARBs, aldosterone antagonists. Post-MI β-blockers, ACEIs, aldosterone antagonists. High CVD risk Thiazide diuretics, β-blockers, ACEIs, CCBs. Diabetes Thiazide diuretics, β-blockers, ACEIs, ARBs, CCBs. Chronic kidney disease ACEIs, ARBs. Recurrent stroke prevention Thiazide diuretics, ACEIs.


First_Aid_Step2

First_Aid_Step2. T AB LE 2.1 -1 5. Common Causes of 2° Hypertension 1° renal disease Often unilateral renal parenchymal disease. Treat with ACEIs, which slow the progression of renal disease. Renal artery stenosis Especially common in patients < 25 and > 50 years of age with recent-onset hypertension. Etiologies include f bromuscular dysplasia (usually in younger patients) and atherosclerosis (usually in older patients). Diagnose with MRA or renal artery Doppler ultrasound. May be treated with angioplasty or stenting. Consider ACEIs as adjunctive or temporary therapy in unilateral disease. (In bilateral disease, ACEIs can accelerate kidney failure by preferential vasodilation of the efferent arteriole.) Open surgery is a second option if angioplasty is not effective or feasible. OCP use Common in women > 35 years of age, obese women, and those with long-standing use. Discontinue OCPs (effect may be delayed). Pheochromocytoma An adrenal gland tumor that secretes epinephrine and norepinephrine, leading


First_Aid_Step2

First_Aid_Step2. 35 years of age, obese women, and those with long-standing use. Discontinue OCPs (effect may be delayed). Pheochromocytoma An adrenal gland tumor that secretes epinephrine and norepinephrine, leading to episodic headache, sweating, and tachycardia. Diagnose with urinary metanephrines and catecholamine levels or plasma metanephrine. Surgical removal of tumor after treatment with both α-blockers and β-blockers. Conn’s syndrome (hyperaldosteronism) Most often 2° to an aldosterone-producing adrenal adenoma. Causes the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis. Surgical removal of tumor. Cushing’s syndrome Due to an ACTH-producing pituitary tumor, an ectopic ACTH-secreting tumor, or cortisol secretion by an adrenal adenoma or carcinoma. (See the Endocrinology chapter for more details.) Surgical removal of tumor. Coarctation of the aorta See the Pediatrics chapter. Surgical repair.


First_Aid_Step2

First_Aid_Step2. nial hemorrhage, papilledema, or ECG changes suggestive of ischemia or pulmonary edema. ■Malignant hypertension: Diagnosed on the basis of progressive renal failure and/or encephalopathy with papilledema. Hypertensive urgencies: Can be treated with oral antihypertensives (e.g., β-blockers, clonidine, ACEIs) with the goal of gradually lowering BP over 24–48 hours (see Tables 2.1-16 and 2.1-17). Hypertensive emergencies: Treat with IV medications (labetalol, nitroprusside, nicardipine) with the goal of lowering mean arterial pressure by no more than 25% over the first two hours to prevent cerebral hypoperfusion or coronary insufficiency. T AB LE 2.1 -1 6. Major Classes of Antihypertensive Agents


First_Aid_Step2

First_Aid_Step2. Diuretics Thiazide, loop, K+ sparing ↓ extracellular fuid volume and thereby ↓ vascular resistance. Hypokalemia (not with K+ sparing), hyperglycemia, hyperlipidemia, hyperuricemia, azotemia. β-adrenergic blockers (β-blockers) Propranolol, metoprolol, nadolol, atenolol, timolol, carvedilol, labetalol ↓ cardiac contractility and renin release. Bronchospasm (in severe active asthma), bradycardia, CHF exacerbation, impotence, fatigue, depression. Centrally acting adrenergic agonists Methyldopa, clonidine Inhibit the sympathetic nervous system via central α2-adrenergic receptors. Somnolence, orthostatic hypotension, impotence, rebound hypertension. α1-adrenergic blockers Prazosin, terazosin, phenoxybenzamine Cause vasodilation by blocking actions of norepinephrine on vascular smooth muscle. Orthostatic hypotension. CCBs Dihydropyridines (nifedipine, felodipine, amlodipine), nondihydropyridines (diltiazem, verapamil) ↓ smooth muscle tone and cause vasodilation; may also ↓ cardiac output.


First_Aid_Step2

First_Aid_Step2. Orthostatic hypotension. CCBs Dihydropyridines (nifedipine, felodipine, amlodipine), nondihydropyridines (diltiazem, verapamil) ↓ smooth muscle tone and cause vasodilation; may also ↓ cardiac output. Dihydropyridines: Headache, fushing, peripheral edema. Nondihydropyridines: ↓ contractility. Vasodilators Hydralazine, minoxidil ↓ peripheral resistance by dilating arteries/arterioles. Hydralazine: Headache, lupus-like syndrome. Minoxidil: Orthostasis, hirsutism. Captopril, enalapril, fosinopril, benazepril, lisinopril Block aldosterone formation, reducing peripheral resistance and salt/water retention. Cough, rashes, leukopenia, hyperkalemia. Losartan, valsartan, irbesartan Block aldosterone effects, reducing peripheral resistance and salt/water retention. Rashes, leukopenia, and hyperkalemia but no cough. ACEIs ARBs


First_Aid_Step2

First_Aid_Step2. Results from acute or chronic pericardial insults; may lead to pericardial effusion. Inﬂammation of the pericardial sac. Can compromise cardiac output via tamponade or constrictive pericarditis. Most commonly idiopathic, although known etiologies include viral infection, TB, SLE, uremia, drugs, radiation, and neoplasms. May also occur after MI (either within days after MI or as a delayed phenomenon, i.e., Dressler’s syndrome) or open heart surgery. TABLE 2.1-17. Antihypertensive Agents for Specifc Patient Populations Diabetes with proteinuria ACEIs or ARBs. CHF β-blockers, ACEIs or ARBs, diuretics (including spironolactone). Isolated systolic hypertension Diuretics are preferred; long-acting dihydropyridines. MI β-blockers without intrinsic sympathomimetic activity; ACEIs. Osteoporosis Thiazide diuretics. BPH α1-adrenergic blockers. May present with pleuritic chest pain, dyspnea, cough, and fever. Chest pain tends to worsen in the supine position and with inspiration.


First_Aid_Step2

First_Aid_Step2. May present with pleuritic chest pain, dyspnea, cough, and fever. Chest pain tends to worsen in the supine position and with inspiration. Exam may reveal a pericardial friction rub, elevated JVP, and pulsus paradoxus (a ↓ in systolic BP > 10 mmHg on inspiration). CXR, ECG, and echocardiogram to rule out MI and pneumonia. ECG changes include diffuse ST-segment elevation and PR-segment depressions followed by T-wave inversions (see Figure 2.1-7). Pericardial thickening or effusion may be evident on echocardiography. Address the underlying cause (e.g., corticosteroids/immunosuppressants for SLE, dialysis for uremia) or symptoms (e.g., ASA for post-MI pericarditis, ASA/NSAIDs for viral pericarditis). Avoid corticosteroids within a few days after MI, as they can predispose to ventricular wall rupture. Pericardial effusions without symptoms can be followed, but evidence of tamponade requires pericardiocentesis, with continuous drainage as needed.


First_Aid_Step2

First_Aid_Step2. Pericardial effusions without symptoms can be followed, but evidence of tamponade requires pericardiocentesis, with continuous drainage as needed. Excess ﬂuid in the pericardial sac, leading to compromised ventricular filling and ↓ cardiac output. The condition is more closely related to the rate of ﬂ uid formation than to the size of the effusion. Risk factors include pericarditis, malignancy, SLE, TB, and trauma (commonly stab wounds medial to the left nipple). ■Presents with fatigue, dyspnea, anxiety, tachycardia, and tachypnea that can rapidly progress to shock and death. Causes of pericarditis— Beck’s triad can diagnose acute cardiac tamponade: F IGU R E 2.1 -7. Acute pericarditis.


First_Aid_Step2

First_Aid_Step2. Causes of pericarditis— Beck’s triad can diagnose acute cardiac tamponade: F IGU R E 2.1 -7. Acute pericarditis. Diffuse ST-segment elevations in multiple leads not consistent with any discrete coronary vas cular territory and PR-segment depressions. (Reproduced, with permission, from Gomella LG et al. Clinician’s Pocket Reference, 11th ed. New York: McGraw-Hill, 2006: Fig. 19-34.) ■Examination of a patient with acute tamponade may reveal Beck’s triad (hypotension, distant heart sounds, and JVD), a narrow pulse pressure, pulsus paradoxus, and Kussmaul’s sign (JVD on inspiration). Echocardiogram shows right atrial and right ventricular diastolic collapse. CXR shows an enlarged, globular heart. If present on ECG, electrical alternans is diagnostic. Aggressive volume expansion with IV ﬂ uids. Urgent pericardiocentesis (aspirate will be nonclotting blood). Decompensation may warrant balloon pericardiotomy and pericardial window.


First_Aid_Step2

First_Aid_Step2. Aggressive volume expansion with IV ﬂ uids. Urgent pericardiocentesis (aspirate will be nonclotting blood). Decompensation may warrant balloon pericardiotomy and pericardial window. Until recently, rheumatic fever (which affects the mitral valve more often than the aortic valve) was the most common cause of valvular heart disease in U.S. adults; the leading cause is now mechanical degeneration. Subtypes are listed in Table 2.1-18 along with their etiologies, presentation, diagnosis, and treatment. Aortic aneurysms are most commonly associated with atherosclerosis. Most are abdominal, and > 90% originate below the renal arteries. Usually asymptomatic and discovered incidentally on exam or radiologic study. Risk factors include hypertension, high cholesterol, other vascular disease, a family history, smoking, gender (males > females), and age. Exam demonstrates a pulsatile abdominal mass or abdominal bruits.


First_Aid_Step2

First_Aid_Step2. Exam demonstrates a pulsatile abdominal mass or abdominal bruits. Ruptured aneurysm leads to hypotension and severe, tearing abdominal pain that radiates to the back. Abdominal ultrasound for diagnosis or to follow an aneurysm over time. CT may be useful to determine the precise anatomy. In asymptomatic patients, monitoring is appropriate for lesions < 5 cm. Surgical repair is indicated if the lesion is > 5.5 cm (abdominal), > 6 cm (thoracic), or smaller but rapidly enlarging. Emergent surgery for symptomatic or ruptured aneurysms. A transverse tear in the intima of a vessel that results in blood entering the media, creating a false lumen and leading to a hematoma that propagates longitudinally. Most commonly 2° to hypertension. The most common sites of origin are above the aortic valve and distal to the left subclavian artery. Most often occurs at 40–60 years of age, with a greater frequency in males than in females.


First_Aid_Step2

First_Aid_Step2. Aortic aneurysm is most often associated with atherosclerosis, while aortic dissection is commonly linked to hypertension. TABLE 2.1-18. Types of Valvular Heart Disease


First_Aid_Step2

First_Aid_Step2. Aortic stenosis Most often seen in the elderly. Unicuspid and bicuspid valves can lead to symptoms in childhood and adolescence. May be asymptomatic for years despite signif cant stenosis. Once symptomatic, usually progresses from angina to syncope to CHF to death within f ve years. Cx (also indications for valve replacements): ACS—Angina, CHF, Syncope. PE: Pulsus parvus et tardus (weak, delated carotid upstroke) and a single or paradoxically split S2 sound; systolic murmur radiating to the carotids. Dx: Echocardiography. Valve replacement. Balloon valvuloplasty can bridge patients to aortic valve replacement but is not def nitive treatment. Aortic regurgitation Acute: Infective endocarditis, aortic dissection, chest trauma. Chronic: Valve malformations, rheumatic fever, connective tissue disorders. Causes: CREAM— Congenital Rheumatic damage, Endocarditis, Aortic dissection/ Aortic root dilatation, Marfan’s syndrome. Acute: Rapid onset of pulmonary congestion, cardiogenic shock, and


First_Aid_Step2

First_Aid_Step2. disorders. Causes: CREAM— Congenital Rheumatic damage, Endocarditis, Aortic dissection/ Aortic root dilatation, Marfan’s syndrome. Acute: Rapid onset of pulmonary congestion, cardiogenic shock, and severe dyspnea. Chronic: Slowly progressive onset of dyspnea on exertion, orthopnea, and PND. PE: Blowing diastolic murmur at the left sternal border, mid-diastolic rumble (Austin Flint murmur), and midsystolic apical murmur. Widened pulse pressure causes de Musset’s sign (head bob with heartbeat), Corrigan’s sign (water-hammer pulse), and Duroziez’s sign (femoral bruit). Dx: Echocardiography. Vasodilator therapy (dihydropyridines or ACEIs) for isolated aortic regurgitation until symptoms become severe enough to warrant valve replacement. Mitral valve stenosis The most common etiology continues to be rheumatic fever. Symptoms range from dyspnea, orthopnea, and PND to infective endocarditis and arrhythmias. PE: Opening snap and mid-diastolic murmur at apex; pulmonary edema. Dx:


First_Aid_Step2

First_Aid_Step2. continues to be rheumatic fever. Symptoms range from dyspnea, orthopnea, and PND to infective endocarditis and arrhythmias. PE: Opening snap and mid-diastolic murmur at apex; pulmonary edema. Dx: Echocardiography. Antiarrhythmics (digoxin, β-blockers) for symptomatic relief; mitral balloon valvotomy and valve replacement are effective for severe cases. Mitral valve regurgitation Primarily 2° to rheumatic fever or chordae tendineae rupture after MI. Patients present with dyspnea, orthopnea, and fatigue. PE: Holosystolic murmur radiating to axillae. Dx: Echocardiography will demonstrate regurgitant f ow; angiography can assess the severity of disease. Antiarrhythmics if necessary (AF is common with LAE; nitrates and diuretics to ↓ preload).


First_Aid_Step2

First_Aid_Step2. Sudden tearing/ripping pain in the anterior chest in ascending dissection; interscapular back pain in descending dissection. The patient is typically hypertensive. If a patient is hypotensive, consider pericardial tamponade, hypovolemia from blood loss, or acute MI from involvement of the coronary arteries. Asymmetric pulses and BP measurements are indicative of aortic dissection. Signs of pericarditis or pericardial tamponade may be seen; a murmur of aortic regurgitation may be heard if the aortic valve is involved with a proximal dissection. Neurologic deficits may be seen if the aortic arch or spinal arteries are involved. ECG, CXR (shows widening of the mediastinum, cardiomegaly, or new left pleural effusion). CT angiography is the gold standard of imaging. TEE can provide details of the thoracic aorta, the proximal coronary arteries, the origins of arch vessels, the presence of a pericardial effusion, and aortic valve integrity.


First_Aid_Step2

First_Aid_Step2. TEE can provide details of the thoracic aorta, the proximal coronary arteries, the origins of arch vessels, the presence of a pericardial effusion, and aortic valve integrity. There are two systems of classification for aortic dissection: DeBakey system: Classifies dissections as involving both the ascending and descending aorta (type I), confined to the ascending aorta (type II), or confined to the descending aorta (type III). Stanford system: Classifies dissection of the ascending aorta as type A and all others as type B. Monitor and medically manage BP and heart rate as necessary. Do not give thrombolytics. If the dissection involves the ascending aorta, it is a surgical emergency; descending dissections can often be managed with BP and heart rate control. Ascending aortic dissections are surgical emergencies, but descending dissections can often be treated medically.


First_Aid_Step2

First_Aid_Step2. Ascending aortic dissections are surgical emergencies, but descending dissections can often be treated medically. Clot formation in the large veins of the extremities or pelvis. The classic Virchow’s triad of risk factors includes venous stasis (e.g., from plane ﬂ ights, bed rest, or incompetent venous valves in the lower extremities), endothelial trauma (injury to the lower extremities), and hypercoagulable states (e.g., malignancy, pregnancy, OCP use). Presents with unilateral lower extremity pain, erythema, and swelling. Homans’ sign is calf tenderness with passive foot dorsiﬂexion (poor sensitivity and specificity for DVT). Doppler ultrasound; spiral CT or V/Q scan may be used to evaluate for pulmonary embolism (see Figure 2.1-8). Virchow’s triad: hemostasis, trauma (endothelial damage), hypercoagulability. A negative D-dimer test can be used to rule out the possibility of pulmonary embolism in low-risk patients.


First_Aid_Step2

First_Aid_Step2. Virchow’s triad: hemostasis, trauma (endothelial damage), hypercoagulability. A negative D-dimer test can be used to rule out the possibility of pulmonary embolism in low-risk patients. F IGU R E 2.1 -8. Algorithm for diagnostic imaging of DVT and PE. (Reproduced, with permission, from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008: Fig. 256-1.) Initial anticoagulation with IV unfractionated heparin or SQ lowmolecular-weight heparin followed by PO warfarin for a total of 3–6 months. Consider an IVC filter in patients with contraindications to anticoagulation. Hospitalized patients should receive DVT prophylaxis consisting of exercise as tolerated, anti-thromboembolic stockings, and SQ unfractionated heparin or low-molecular-weight heparin.


First_Aid_Step2

First_Aid_Step2. Hospitalized patients should receive DVT prophylaxis consisting of exercise as tolerated, anti-thromboembolic stockings, and SQ unfractionated heparin or low-molecular-weight heparin. Occlusion of the blood supply to the extremities by atherosclerotic plaque. The lower extremities are most commonly affected. Clinical manifestations depend on the vessels involved, the extent and rate of obstruction, and the presence of collateral blood ﬂ ow. Presents with intermittent claudication (reproducible leg pain that occurs with walking and is always relieved with rest). As the disease progresses, pain occurs at rest and affects the distal extremities. Dorsal foot ulcerations may develop 2° to poor perfusion. A painful, cold, numb foot is characteristic of critical limb ischemia. Aortoiliac disease: Associated with Leriche’s syndrome (buttock claudication, ↓ femoral pulses, male impotence). Femoropopliteal disease: Calf claudication; pulses below the femoral artery are absent.


First_Aid_Step2

First_Aid_Step2. Femoropopliteal disease: Calf claudication; pulses below the femoral artery are absent. Acute ischemia: Most often caused by embolization from the heart; acute occlusions commonly occur at bifurcations distal to the last palpable pulse. May also be 2° to cholesterol atheroembolism (“blue toe syndrome”). ■Severe chronic ischemia: Lack of blood perfusion leads to muscle atrophy, pallor, cyanosis, hair loss, and gangrene/necrosis. Carefully palpate pulses and auscultate for bruits. Measurement of ankle and brachial systolic BP (ankle-brachial index, or ABI) can provide objective evidence of atherosclerosis (rest pain usually occurs with an ABI < 0.4). A high ABI can indicate calcification of the arteries. Doppler ultrasound helps identify stenosis and occlusion. Doppler ankle systolic pressure readings that are > 90% of brachial readings are normal. Arteriography and digital subtraction angiography are necessary for surgical evaluation.


First_Aid_Step2

First_Aid_Step2. Arteriography and digital subtraction angiography are necessary for surgical evaluation. Control underlying conditions (e.g., DM, other cardiac risk factors); eliminate tobacco and institute careful hygiene and foot care. Exercise helps develop collateral circulation. ASA, cilostazol, and thromboxane inhibitors may improve symptoms; anticoagulants may prevent clot formation. Angioplasty and stenting have a variable success rate that is dependent on the area of occlusion. Surgery (arterial bypass) or amputation can be employed when conservation treatment fails. Avoid β-blockers in peripheral arterial disease 2° to B2-mediated peripheral vasoconstriction.


First_Aid_Step2

First_Aid_Step2. Surgery (arterial bypass) or amputation can be employed when conservation treatment fails. Avoid β-blockers in peripheral arterial disease 2° to B2-mediated peripheral vasoconstriction. Disruption of the lymphatic circulation that results in peripheral edema and chronic infection of the extremities. Often a complication of surgery involving lymph node dissection. In underdeveloped countries, parasitic infection can lead to lymphatic obstruction, resulting in edema. Congenital malformations of the lymphatic system, such as Milroy’s disease, can present with lymphedema in childhood. Postmastectomy patients present with unexplained swelling of the upper extremity. Immigrants present with progressive swelling of the lower extremities bilaterally with no cardiac abnormalities (i.e., filariasis). Children present with progressive, bilateral swelling of the extremities. Diagnosis is clinical. Rule out other causes of edema, such as cardiac and metabolic disorders.


First_Aid_Step2

First_Aid_Step2. Children present with progressive, bilateral swelling of the extremities. Diagnosis is clinical. Rule out other causes of edema, such as cardiac and metabolic disorders. Directed at symptom management, as no curative treatment exists. Agents such as diuretics are ineffective and relatively contraindicated. Exercise, massage therapy, and pressure garments to mobilize and limit ﬂuid accumulation may be of help. ■Maintain vigilance for cellulitis with prompt gram-antibiotic coverage for infection. Cardiac syncope is associated with one-year sudden cardiac death rates of up to 40%. A sudden, temporary loss of consciousness and postural tone 2° to cerebral hypoperfusion. Etiologies are either cardiac or noncardiac: Cardiac: Valvular lesions, arrhythmias, pulmonary embolism, cardiac tamponade, aortic dissection.


First_Aid_Step2

First_Aid_Step2. Cardiac: Valvular lesions, arrhythmias, pulmonary embolism, cardiac tamponade, aortic dissection. Noncardiac: Orthostatic/hypovolemic hypotension, neurologic (TIA, stroke), metabolic abnormalities, neurocardiogenic syndromes (e.g., vasovagal/micturition syncope), psychiatric. Rule out many potential etiologies. Triggers, prodromal symptoms, and associated symptoms should be investigated. Cardiac causes of syncope are typically associated with very brief or absent prodromal symptoms, a history of exertion, lack of association with changes in position, and/or a history of cardiac disease. Depending on the suspected etiology, Holter monitors or event recorders (arrhythmias), echocardiograms (structural abnormalities), and stress tests (ischemia) can be useful diagnostic tools. Tailored to the etiology. Layers of the Skin 75 Common Terminology 75 Allergic and Immune-Mediated Disorders 75


First_Aid_Step2

First_Aid_Step2. Tailored to the etiology. Layers of the Skin 75 Common Terminology 75 Allergic and Immune-Mediated Disorders 75 The skin consists of three layers: the epidermis, the dermis, and subcutaneous tissue (see Figure 2.2-1). Table 2.2-1 describes pertinent components of the epidermis, the dermis, and the various skin appendages. Table 2.2-2 outlines terms frequently used to describe common manifestations of dermatologic disease. Table 2.2-3 outlines the types and mechanisms of hypersensitivity reactions. Descriptions of common allergic and immune-mediated disorders follow. A relapsing inﬂammatory skin disorder that is common in infancy and presents differently in different age groups. It is characterized by pruritus that leads to lichenification (see Figure 2.2-2). Eczema is the “itch that rashes.” Atopic dermatitis is commonly associated with asthma and allergic rhinitis. Patients are at ↑ risk of 2° bacterial and viral infection.


First_Aid_Step2

First_Aid_Step2. Eczema is the “itch that rashes.” Atopic dermatitis is commonly associated with asthma and allergic rhinitis. Patients are at ↑ risk of 2° bacterial and viral infection. Triggers include climate, food, contact with allergens or physical or chemical irritants, and emotional factors. FIGURE 2.2-1. Layers of the skin. (Adapted, with permission, from Hardman JG et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York: McGraw-Hill, 2001: 1805.) TABLE 2.2-1. Components of Skin Layers Keratinocytes Melanocytes Langerhans cells Merkel cells Fibroblasts (synthesize collagen, elastin, and ground substance) Mast cells Monocytes/macrophages Vessels/lymphatics Nerves Smooth muscle Nails (nail matrix, nail fold, nail plate, nail bed) Hair complex (hair follicles, sebaceous glands, apocrine glands) T AB LE 2.2-2. Common Terms Used to Describe Skin Lesions


First_Aid_Step2

First_Aid_Step2. Macule A fat lesion that differs in color from surrounding skin (< 1 cm in diameter). Papule An elevated solid lesion that is generally small (< 5 mm in diameter). Patch A small, circumscribed area differing in color from the surrounding surface (> 1 cm in diameter). Plaque An elevated solid lesion (> 5 mm in diameter). Cyst An epithelial-lined sac containing fuid or semisolid material. Vesicle A f uid-flled, very small (< 0.5-mm), elevated lesion. Bulla A large vesicle (> 5 mm). Wheal (or hive) An area of localized edema that follows vascular leakage and usually disappears within hours. Erosion A circumscribed, superfcial depression resulting from the loss of some or all of the epidermis. Ulcer A deeper depression resulting from destruction of the epidermis and upper dermis. Scale Abnormal shedding or accumulation of stratum corneum in f akes. Crust A hardened deposit of dried serum, blood, or purulent exudates. Lichenifcation Thickening of the epidermis. Scar A healing defect of the


First_Aid_Step2

First_Aid_Step2. shedding or accumulation of stratum corneum in f akes. Crust A hardened deposit of dried serum, blood, or purulent exudates. Lichenifcation Thickening of the epidermis. Scar A healing defect of the dermis (the epidermis alone heals without a scar).


First_Aid_Step2

First_Aid_Step2. T AB LE 2.2-3. Types and Mechanisms of Hypersensitivity Reactions


First_Aid_Step2

First_Aid_Step2. Type I Anaphylactic and atopic: Antigen cross-links IgE on presensitized mast cells and basophils, triggering the release of vasoactive amines (i.e., histamine). Reaction develops rapidly after antigen exposure as a result of preformed antibody. Examples include anaphylaxis, asthma, urticarial drug reactions, and local wheal and f are. First and Fast (anaphylaxis). Types I, II, and III are all antibody, or B-cell, mediated. Type II Cytotoxic: IgM and IgG bind to antigen on an “enemy” cell, leading to lysis (by complement) or phagocytosis. Examples include autoimmune hemolytic anemia, Rh disease (erythroblastosis fetalis), Goodpasture’s syndrome, and rheumatic fever. Cy-2-toxic. Antibody and complement lead to membrane attack complex (MAC). Type III Immune complex: Antigen-antibody complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes. Examples include polyarteritis nodosa, immune complex glomerulonephritis, SLE, and rheumatoid arthritis.


First_Aid_Step2

First_Aid_Step2. activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes. Examples include polyarteritis nodosa, immune complex glomerulonephritis, SLE, and rheumatoid arthritis. Serum sickness: An immune complex disease (type III) in which antibodies to the foreign proteins are produced (takes f ve days). Immune complexes form and are deposited in membranes, where they fx complement (leading to tissue damage). More common than Arthus reaction. Arthus reaction: A local subacute antibody-mediated hypersensitivity (type III) reaction. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin. Characterized by edema, necrosis, and activation of complement. Examples include hypersensitivity pneumonitis and thermophilic actinomycetes. Imagine an immune complex as three things stuck together: antigen-antibody complement. Includes many glomerulonephritides and vasculitides. Most serum sickness is now caused by drugs (not serum).


First_Aid_Step2

First_Aid_Step2. Imagine an immune complex as three things stuck together: antigen-antibody complement. Includes many glomerulonephritides and vasculitides. Most serum sickness is now caused by drugs (not serum). Fever, urticaria, arthralgias, proteinuria, and lymphadenopathy occur 5–10 days after antigen exposure. Antigen-antibody complexes cause the Arthus reaction. Type IV Delayed (cell-mediated) type: Sensitized T lymphocytes encounter antigen and then release lymphokines (leading to macrophage activation). Examples include TB skin tests, transplant rejection, and contact dermatitis (e.g., poison ivy, poison oak). 4th and last—delayed. Cell mediated, not antibody mediated; therefore, it is not transferable by serum.


First_Aid_Step2

First_Aid_Step2. Clinical manifestations by age group are as follows: Infants: Erythematous, weeping, pruritic patches on the face, scalp, and diaper area. Children: Dry, scaly, pruritic, excoriated patches in the ﬂ exural areas and neck. Adults: Lichenification and dry, fissured skin, often limited to the hands. FIGURE 2.2-2. Atopic dermatitis. Erythema toxicum of the newborn resembles eczema, presenting with red papules/ vesicles with surrounding erythema. ↑ eosinophils will be seen on biopsy. This typically benign rash rarely appears after f ve days of age and is usually gone in 7–14 days; treatment is typically observation. Hyperpigmentation, lichenification, and scaling are seen in the antecubital fossae. (Courtesy of Robert Swerlick, MD, as published in Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008.)


First_Aid_Step2

First_Aid_Step2. Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008.) Diagnosis is made clinically. Patients may have mild eosinophilia and ↑ IgE. Rule out seborrheic dermatitis, contact dermatitis, pityriasis rosea, drug eruption, and cutaneous T-cell lymphoma. Prophylactic measures include use of nondrying soaps, application of moisturizers, and avoidance of known triggers. Treat with topical corticosteroids (avoid systemic steroids in light of their side effect profile), PUVA, and topical immunomodulators (e.g., tacrolimus, pimecrolimus). Topical corticosteroids should not be used for longer than 2–3 weeks. A type IV hypersensitivity reaction that results from contact with an allergen to which the patient has previously been exposed and sensitized. Dermatitis develops when the patient is reexposed to the allergen or to a cross-reactive compound. More common in adults than in children.


First_Aid_Step2

First_Aid_Step2. Commonly presents with pruritus and rash, but can also present with edema, fever, and lymphadenopathy. Frequently implicated allergens include poison ivy, poison oak, nickel, soaps, detergents, cosmetics, and rubber products containing latex (e.g., gloves and elastic bands in clothing). Characteristic distributions involve areas where makeup, clothing, perfume, nickel jewelry, and plants come into contact with the skin. The dermatitis begins in the area of contact with the antigen, with its appearance varying with the acuity of the lesion. Acute: Approximately 24–48 hours after an allergic contact, the skin becomes erythematous, presenting with tiny blisters followed by scale and crusts. Lesions are intensely pruritic. Subacute: Results from episodic exposure or a weak allergen. Lesions are less “angry appearing” than those of an acute inﬂ ammatory rash, and some lichenification is seen.


First_Aid_Step2

First_Aid_Step2. Subacute: Results from episodic exposure or a weak allergen. Lesions are less “angry appearing” than those of an acute inﬂ ammatory rash, and some lichenification is seen. Chronic: Results from extended exposure to an allergen. Characterized by erythema and lichenification with fissuring, often with superimposed acute dermatitis. The overall shape of the rash often mimics that of the exposing object (see Figure 2.2-3), but it can also spread over the body via transfer of allergen by the hands or via circulating T lymphocytes. Patients are at ↑ risk of 2° infection. Diagnosed by clinical impression. A patch test can be used to establish the causative allergen after the acute-phase rash has been treated. The differential includes atopic dermatitis, seborrheic dermatitis, impetigo, HSV, herpes zoster, and fungal infection. Prophylaxis consists of avoidance of the offending allergen.


First_Aid_Step2

First_Aid_Step2. Prophylaxis consists of avoidance of the offending allergen. Treat with topical or systemic corticosteroids as needed and with cool, wet compresses to relieve and debride the skin. The pathogenesis of contact dermatitis involves allergenic molecules that are passed through the epidermis and taken up by Langerhans cells, which carry them to the lymph nodes and expose them to T lymphocytes. FIGURE 2.2-3. Contact dermatitis. Shown above are erythematous papules and vesicles with serous weeping localized to areas of contact with the offending agent. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 3.) Suspect HIV in a young person with severe seborrheic dermatitis.


First_Aid_Step2

First_Aid_Step2. Suspect HIV in a young person with severe seborrheic dermatitis. A common disease that may be caused by Pityrosporum ovale, a generally harmless yeast found in sebum and hair follicles. It has a predilection for areas with oily skin such as the scalp, eyebrows, nasolabial folds, and midchest. The appearance of rash varies with age: Infants: Presents as a severe, red diaper rash with yellow scale, erosions, and blisters. A thick crust (“cradle cap”) may be seen on the scalp. Children/adults: Red, scaly patches are seen around the ears, eyebrows, nasolabial fold, midchest, and scalp. The rash is more localized and less dramatic than that seen in infants. Patients with HIV/AIDS can develop severe seborrheic dermatitis or an overlapping syndrome of severe seborrheic dermatitis, psoriasis, psoriatic arthritis, and even Reiter’s syndrome. Diagnosed by clinical impression. Rule out contact dermatitis and psoriasis.


First_Aid_Step2

First_Aid_Step2. Diagnosed by clinical impression. Rule out contact dermatitis and psoriasis. Treatment consists of selenium sulfide or zinc pyrithione shampoos for the scalp, and topical antifungals and/or topical corticosteroids for other areas. Low-concentration coal tar shampoos are still available despite concerns about carcinogenicity. A T-cell-mediated inﬂammatory dermatosis characterized by erythematous patches and silvery scales due to dermal inﬂammation and epidermal hyperplasia. Five percent of patients also have a seronegative arthritis. The condition usually starts in puberty or young adulthood, and its incidence is 2–4%. The typical lesion is a round, sharply bordered erythematous patch with silvery scales (see Figure 2.2-4A). Lesions are classically found on the extensor surfaces, including the elbows, knees, scalp, and lumbosacral regions.


First_Aid_Step2

First_Aid_Step2. Lesions are classically found on the extensor surfaces, including the elbows, knees, scalp, and lumbosacral regions. Lesions may initially appear very small (guttate) but may slowly enlarge and become conﬂuent. Psoriatic nails feature pitting, “oil spots,” and onycholysis, or lifting of the nail plate (see Figure 2.2-4B). Psoriatic lesions can be provoked by local irritation or by trauma (Koebner’s phenomenon). Streptococcal infection can lead to cutaneous immune complex deposition, which triggers guttate psoriasis. Some medications, such as β-blockers, lithium, and ACEIs, can also induce psoriasis. Psoriatic arthritis usually begins in the hands with “sausage digits,” but the knees, wrists and ankles as well as the lumbosacral region may also be affected. Arthritic patients with spinal involvement are usually HLAB27 .


First_Aid_Step2

First_Aid_Step2. When pustular psoriasis, a less common form, is generalized, it can be life threatening, presenting with fever, electrolyte abnormalities, and loss of serum proteins. AB FIGURE 2.2-4. Psoriasis. (A) Skin changes. The classic sharply demarcated plaques with silvery scales are commonly located on the extensor surfaces (e.g., elbows, knees). (B) Nail changes. Note the pitting, onycholysis, and “oil spots.” (Reproduced, with permission, from Hur witz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 15, 18.) Clinical impression is usually sufficient for diagnosis. Classically presents with the Auspitz sign (bleeding when scale is scraped), but biopsy can be useful. Histology classically shows a thickened epidermis, elongated rete ridges, an absent granular cell layer, preservation of nuclei, and a sterile neutrophilic infiltrate (Munro’s microabscess) in the stratum corneum.


First_Aid_Step2

First_Aid_Step2. Treat with topical steroids combined with keratolytic agents, tar, or anthralin along with UV therapy, including PUVA. Methotrexate may be used for severe cases. Retinoids (vitamin A derivatives) may also be used. Arthritis should be treated first with NSAIDs and then with methotrexate if necessary. Systemic corticosteroids should be avoided, as tapering can induce psoriatic ﬂ ares. Recently, biologic agents such as TNF-α inhibitors have proven effective in severe psoriatic arthritis and psoriasis. Urticaria is characterized by superficial, intense edema in a localized area. It is usually acute but can also be chronic (lasting > 6 weeks). The condition results from the release of vasoactive substances (histamine, prostaglandins) from mast cells in a type I hypersensitivity response. ■Hives can range in severity from a few itchy bumps to life-threatening anaphylaxis.


First_Aid_Step2

First_Aid_Step2. ■Hives can range in severity from a few itchy bumps to life-threatening anaphylaxis. The typical lesion is an elevated papule or plaque that is reddish or white and variable in size. Lesions are widespread and last a few hours. In severe allergic reactions, extracutaneous manifestations can include tongue swelling, angioedema (deeper, more diffuse swelling), asthma, GI symptoms, joint swelling, and fever. Acute urticaria is a response to a trigger that may be a food, drug, virus, insect bite, or physical stimulus. Chronic urticaria is usually idiopathic. Diagnosed by clinical impression and patient report. Biopsy demonstrates perivascular edema. It can often be difficult to determine the cause. Treat with systemic antihistamines. Topical medications are of no benefit.


First_Aid_Step2

First_Aid_Step2. Treat with systemic antihistamines. Topical medications are of no benefit. Maintain a high suspicion for a cutaneous drug reaction in patients who are hospitalized and develop rashes. Such reactions can take many forms, including urticarial, lupus-like, vasculitic, purpuric, lichenoid, and vesicular. Drugs can cause all four types of hypersensitivity reactions, and sometimes the same drug may cause different types of reactions in different patients. Eruptions occur 7–14 days after exposure, so if a patient reacts within a day or two of starting a new drug (i.e., a drug they have never taken before), that drug is probably not the causative agent. Eruptions are generally widespread, relatively symmetrical, and pruritic. Most are relatively short-lived, disappearing within 1–2 weeks following removal of the offending agent.


First_Aid_Step2

First_Aid_Step2. Eruptions are generally widespread, relatively symmetrical, and pruritic. Most are relatively short-lived, disappearing within 1–2 weeks following removal of the offending agent. The exception is fixed drug eruption, which consists of reddish macules or papules that develop in the same area (usually the genitalia, face, or extremities) each time the patient is exposed to the triggering agent. After these lesions resolve, there is often a persistent brown pigmentation. Extreme complications of drug eruptions include erythroderma and toxic epidermal necrolysis (TEN). Diagnosed by clinical impression. Patients may have eosinophilia and eosinophils on histopathology. Discontinue the offending agent; treat symptoms with antihistamines.


First_Aid_Step2

First_Aid_Step2. Diagnosed by clinical impression. Patients may have eosinophilia and eosinophils on histopathology. Discontinue the offending agent; treat symptoms with antihistamines. A cutaneous reaction pattern with classic targetoid lesions that has many triggers and is often recurrent. Although some cases are idiopathic, many are triggered by recurrent HSV infection of the lip. Other common triggers are drugs (e.g., sulfa drugs, anticonvulsants, barbiturates, penicillin, NSAIDs) and mycoplasmal infections. The characteristic lesion has a target appearance (see Figure 2.2-5), but other types of lesions may be seen as well. The disease can occur on mucous membranes, where erosions are seen. Typically, lesions start as erythematous macules that become centrally clear and then develop a blister. The palms and soles are often affected. May be associated with systemic symptoms, including fever, myalgias, headache, and arthralgias (these symptoms may precede eruption).


First_Aid_Step2

First_Aid_Step2. May be associated with systemic symptoms, including fever, myalgias, headache, and arthralgias (these symptoms may precede eruption). In its minor form, the disease is uncomplicated and localized to the skin. However, severe erythema multiforme can lead to TEN or Stevens-Johnson syndrome, in which patients are very ill with involvement of at least two mucosal surfaces. Diagnosed by clinical impression. A history of recurrent labial herpes should be sought in all cases with multiple recurrences. Symptomatic treatment is all that is necessary; systemic corticosteroids are of no benefit. Minor cases can be treated with antipruritics; major cases should be treated as burns. In patients with HSV, suppressive acyclovir may ↓ the frequency of rashes. FIGURE 2.2-5. Erythema multiforme.


First_Aid_Step2

First_Aid_Step2. Minor cases can be treated with antipruritics; major cases should be treated as burns. In patients with HSV, suppressive acyclovir may ↓ the frequency of rashes. FIGURE 2.2-5. Erythema multiforme. Evolving erythematous plaques and papules are seen with a target appearance consisting of a dull red center, a pale zone, and a darker outer ring. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 24.) SJS and TEN may be confused with staphylococcal scalded-skin syndrome (SSSS), another condition in which patients lose widespread sheets of skin. SSSS is usually seen in children < 6 years of age and has an infectious etiology. SJS/TEN is generally seen in adults and is usually caused by a drug reaction. Patients with erythema nodosum may have a falseVDRL (as in SLE).


First_Aid_Step2

First_Aid_Step2. Patients with erythema nodosum may have a falseVDRL (as in SLE). SJS and TEN constitute two different points on the spectrum of life-threatening exfoliative mucocutaneous diseases that are often caused by a drug-induced immunologic reaction. The epidermal separation of SJS involves < 10% of body surface area (BSA), whereas TEN involves > 30% of BSA. Involvement of 10–30% of BSA is often considered SJS/TEN overlap. May be preceded by erythema multiforme, a ﬂulike prodrome, skin tenderness, a maculopapular drug rash, or painful mouth lesions. Often associated with a history of exposure to new drugs, such as penicillin, sulfonamides, seizure medications (e.g., phenytoin, carbamazepine), quinolones, cephalosporins, allopurinol, corticosteroids, or NSAIDs. Exam reveals severe mucosal erosions with widespread erythematous, cutaneous macules or atypical targetoid lesions. The epidermal lesions often become conﬂuent and show a Nikolsky’s sign and epidermal detachment.


First_Aid_Step2

First_Aid_Step2. Mucous membranes of the eyes, mouth, and genitals often become eroded and hemorrhagic as well. SJS: Biopsy shows degeneration of the basal layer of the epidermis and perivascular mononuclear infiltrate with some eosinophils in the papillary dermis. Subepidermal blisters may also be seen. TEN: Biopsy shows full-thickness eosinophilic epidermal necrosis with cell-poor infiltrate; there is a sparse perivascular lymphocytic infiltrate. TEN vs. SSSS: On biopsy, TEN demonstrates full-thickness epidermal damage, whereas SSSS shows only superficial damage. The differential also includes graft-versus-host reaction (usually after bone marrow transplant), radiation therapy, and burns.


First_Aid_Step2

First_Aid_Step2. The differential also includes graft-versus-host reaction (usually after bone marrow transplant), radiation therapy, and burns. Patients have the same complications as burn victims, including thermoregulatory difficulties, electrolyte disturbances, and 2° infections. Treatment includes skin coverage and maintenance of ﬂuid and electrolyte balance. Controversial treatments include systemic corticosteroids in the early stages of SJS/ TEN or IVIG. There is a high risk of mortality. A panniculitis whose triggers include infection (e.g., Streptococcus, Coccidioides, Yersinia, TB), drug reactions (e.g., sulfonamides, various antibiotics, OCPs), and chronic inﬂ ammatory diseases (e.g., sarcoidosis, Crohn’s disease, ulcerative colitis, Behçet’s disease). Painful, erythematous nodules appear on the patient’s lower legs (see Figure 2.2-6) and slowly spread, turning brown or gray. Patients may present with fever and joint pain. FIGURE 2.2-6. Erythema nodosum.


First_Aid_Step2

First_Aid_Step2. FIGURE 2.2-6. Erythema nodosum. Erythematous plaques and nodules are commonly located on pretibial areas. Lesions are pain ful and indurated but heal spontaneously without ulceration. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 132.) Diagnosed by clinical impression. Histology shows nonspecific septal panniculitis. Workup should include an ASO titer, a PPD test in patients who are high risk, a CXR to rule out sarcoid, and a small bowel series to rule out IBD in patients with GI symptoms. Remove the triggering factor and treat the underlying disease where possible. NSAIDs can be used but may lead to erythema multiforme.


First_Aid_Step2

First_Aid_Step2. Remove the triggering factor and treat the underlying disease where possible. NSAIDs can be used but may lead to erythema multiforme. A life-threatening autoimmune condition characterized by an intraepidermal blister leading to widespread painful erosions of the skin and mucous membranes. Antibodies are directed against desmoglein molecules responsible for keratinocyte adherence, leading to loss of cellular attachment. Patients are generally middle-aged (40–60). Initial presentation is with mucous membrane involvement, typically mouth ulcers, with progression to skin involvement. Rarely, an intact blister may be seen, but generally presents only with erosions, often accompanied by crusting, weeping, and 2° infections. Along with the clinical picture, a Nikolsky’s sign (the ability to produce a blister by rubbing skin adjacent to a natural blister) and skin biopsy with immunoﬂ uorescence confirm the diagnosis.


First_Aid_Step2

First_Aid_Step2. Along with the clinical picture, a Nikolsky’s sign (the ability to produce a blister by rubbing skin adjacent to a natural blister) and skin biopsy with immunoﬂ uorescence confirm the diagnosis. Biopsy shows acantholysis (intraepidermal split with free-ﬂ oating keratinocytes in the blister). Immunoﬂ uorescence and ELISA are confirmatory for antidesmoglein antibodies. Long-term treatment is generally required. Initially, systemic corticosteroids are used at high doses in combination with steroid-sparing agents introduced early to ↓ corticosteroid side effects. Steroid-sparing agents include mycophenolate mofetil and azathioprine. Recently, rituximab and IVIG have been successfully used for recalcitrant disease.