First_Aid_for_the_USMLE_Step_1_2023_Compressed_-1-450

["280 SECTION III HIGH-YIELD ORGAN SYSTEMS `\u2009APPROACHING THE ORGAN SYSTEMS In this section, we have divided the High-Yield Facts into the major Organ Systems. Within each Organ System are several subsections, including Embryology, Anatomy, Physiology, Pathology, and Pharmacology. As you progress through each Organ System, refer back to information in the previous subsections to organize these basic science subsections into a \u201cvertically integrated\u201d framework for learning. Below is some general advice for studying the organ systems by these subsections. Embryology Relevant embryology is included in each organ system subsection. Embryology tends to correspond well with the relevant anatomy, especially with regard to congenital malformations. Anatomy Several topics fall under this heading, including gross anatomy, histology, and neuroanatomy. Do not memorize all the small details; however, do not ignore anatomy altogether. Review what you have already learned and what you wish you had learned. Many questions require two or more steps. The first step is to identify a structure on anatomic cross section, electron micrograph, or photomicrograph. The second step may require an understanding of the clinical significance of the structure. While studying, emphasize clinically relevant material. For example, be familiar with gross anatomy and radiologic anatomy \u00adrelated to specific diseases (eg, Pancoast tumor, Horner syndrome), traumatic injuries (eg, fractures, sensory and motor nerve deficits), procedures (eg, lumbar puncture), and common surgeries (eg, cholecystectomy). There are also many questions on the exam involving x-rays, CT scans, and neuro MRI scans. Many students suggest browsing through a general radiology atlas, pathology atlas, and histology atlas. Focus on learning basic anatomy at key levels in the body (eg,\u00a0 sagittal brain MRI; axial CT of the midthorax, abdomen, and pelvis). Basic neuroanatomy (especially pathways, blood supply, and functional anatomy), associated neuropathology, and neurophysiology have good yield. Please note that many of the photographic images in this book are for illustrative purposes and are not necessarily reflective of Step 1 emphasis. Physiology The portion of the examination dealing with physiology is broad and concept oriented and thus does not lend itself as well to fact-based review. Diagrams are often the best study aids, especially given the increasing number of questions requiring the interpretation of diagrams. Learn to apply basic physiologic relationships in a variety of ways (eg, the Fick equation, clearance equations). You are seldom asked to perform complex calculations. Hormones","HIGH-YIELD ORGAN SYSTEMS SECTION III 281 are the focus of many questions; learn where and how they are synthesized, their regulatory mechanisms and sites of action. A large portion of the physiology tested on the USMLE Step 1 is clinically relevant and involves understanding physiologic changes associated with pathologic processes (eg, changes in pulmonary function with COPD). Thus, it is worthwhile to review the physiologic changes that are found with common pathologies of the major organ systems (eg, heart, lungs, kidneys, GI tract) and endocrine glands. Pathology Questions dealing with this discipline are difficult to prepare for because of the sheer volume of material involved. Review the basic principles and hallmark characteristics of the key diseases. Given the clinical orientation of Step 1, it is no longer sufficient to know only the \u201cbuzzword\u201d associations of certain diseases (eg, caf\u00e9-au-lait macules and neurofibromatosis); you must also recognize the clinical descriptions of these high-yield physical exam findings. Given the clinical slant of the USMLE Step 1, it is also important to review the classic presenting signs and symptoms of diseases as well as their associated laboratory findings. Delve into the signs, symptoms, and pathophysiology of major diseases that have a high prevalence in the United States (eg, alcohol use disorder, diabetes, hypertension, heart failure, ischemic heart disease, infectious disease). Be prepared to think one step beyond the simple diagnosis to treatment or complications. The examination includes a number of color photomicrographs and photographs of gross specimens that are presented in the setting of a brief clinical history. However, read the question and the choices carefully before looking at the illustration, because the history will help you identify the pathologic process. Flip through an illustrated pathology textbook, color atlases, and appropriate Web sites in order to look at the pictures in the days before the exam. Pay attention to potential clues such as age, sex, ethnicity, occupation, recent activities and exposures, and specialized lab tests. Pharmacology Preparation for questions on pharmacology is straightforward. Learning all the key drugs and their characteristics (eg, mechanisms, clinical use, and important adverse effects) is high yield. Focus on understanding the prototype drugs in each class. Avoid memorizing obscure derivatives. Learn the \u201cclassic\u201d and distinguishing toxicities of the major drugs. Do not bother with drug dosages or brand names. Reviewing associated biochemistry, physiology, and microbiology can be useful while studying pharmacology. There is a strong emphasis on ANS, CNS, antimicrobial, and cardiovascular agents as well as NSAIDs. Much of the material is clinically relevant. Newer drugs on the market are also fair game. uploaded by medbooksvn","282 SECTION III HIGH-YIELD ORGAN SYSTEMS ` \u2009N O T E S","HIGH-YIELD SYSTEMS Cardiovascular \u201cAs for me, except for an occasional heart attack, I feel as young as I ever `\tEmbryology\t 284 did.\u201d `\tAnatomy\t 288 `\tPhysiology\t 289 \u2014Robert Benchley `\tPathology\t 302 `\tPharmacology\t 321 \u201cHearts will never be practical until they are made unbreakable.\u201d \u2014The Wizard of Oz \u201cAs the arteries grow hard, the heart grows soft.\u201d \u2014H. L. Mencken \u201cNobody has ever measured, not even poets, how much the heart can hold.\u201d \u2014Zelda Fitzgerald \u201cThe art of medicine has its roots in the heart.\u201d \u2014Paracelsus \u201cIt is not the size of the man but the size of his heart that matters.\u201d \u2014Evander Holyfield The cardiovascular system is one of the highest yield areas for the boards and, for some students, may be the most challenging. Focusing on understanding the mechanisms instead of memorizing the details can make a big difference. Pathophysiology of atherosclerosis and heart failure, mechanism of action of drugs (particularly, physiology interactions) and their adverse effects, ECGs of heart blocks, the cardiac cycle, and the Starling curve are some of the more high-yield topics. Differentiating between systolic and diastolic dysfunction is also very important. Heart murmurs and maneuvers that affect these murmurs have also been high yield and may be asked in a multimedia format. 283 uploaded by medbooksvn","284 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Embryology ` \u2009C A R D I O VA S C UL A R \u2014 E M B R Y O LO G Y Heart morphogenesis First functional organ in vertebrate embryos; beats spontaneously by week 4 of development. Cardiac looping Primary heart tube loops to establish left-right Defect in left-right dynein (involved in left-right polarity; begins in week 4 of development. asymmetry) can lead to dextrocardia, as seen in Kartagener syndrome. Septation of the chambers Atria Septum primum grows toward endocardial 6. \u0007Septum primum closes against septum cushions, narrowing ostium primum. secundum, sealing the foramen ovale soon Ostium secundum forms in septum primum after birth because of \u008f LA pressure and \u0090 RA due to cell death (ostium primum regresses). pressure. Septum secundum develops on the right 7. \u0007Septum secundum and septum primum fuse side of septum primum, as ostium secundum during infancy\/early childhood, forming the maintains right-to-left shunt. atrial septum. S\u0007 eptum secundum expands and covers most Patent foramen ovale\u2014caused by failure of of ostium secundum. The residual foramen is septum primum and septum secundum the foramen ovale. to fuse after birth; most are left untreated. R\u0007 emaining portion of septum primum forms Can lead to paradoxical emboli (venous the one-way valve of the foramen ovale. thromboemboli entering the systemic arterial circulation through right-to-left shunt) as can occur in atrial septal defect (ASD). Septum RA LA Dorsal Ostium Septum Developing primum endocardial secundum primum septum cushion Ostium Ostium secundum primum primum Ostium secundum Septum primum Septum Ostium Degenerating secundum secundum septum primum Foramen Septum Foramen ovale primum ovale Septum (closed) secundum","Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Embryology SEC TION III 285 Heart morphogenesis (continued) Ventricles Muscular interventricular septum forms. Ventricular septal defect\u2014most common \u2002\u2002 Opening is called interventricular foramen. congenital cardiac anomaly, usually occurs in membranous septum. A\u0007 orticopulmonary septum rotates and fuses with muscular ventricular septum to form membranous interventricular septum, closing interventricular foramen. \u0007Growth of endocardial cushions separates atria from ventricles and contributes to both atrial septation and membranous portion of the interventricular septum. Aorticopulmonary septum Interventricular RA LA RA LA RA LA foramen Membranous Outflow tract Atrioventricular interventricular formation canals septum Valve development Muscular Conotruncal abnormalities associated with interventricular failure of neural crest cells to migrate: \u0083\t Transposition of great arteries. septum \u0083\t Tetralogy of Fallot. \u0083\t Persistent truncus arteriosus. Neural crest cell migrations \u008e\u00a0truncal and bulbar ridges that spiral and fuse to form Valvular anomalies may be stenotic, regurgitant, aorticopulmonary septum \u008e\u00a0ascending aorta atretic (eg, tricuspid atresia), or displaced (eg, and pulmonary trunk. Ebstein anomaly). Aortic\/pulmonary: derived from endocardial cushions of outflow tract. Mitral\/tricuspid: derived from fused endocardial cushions of the AV canal. Aortic arch derivatives Develop into arterial system. External Right recurrent 1st carotid artery laryngeal nerve 2nd Part of maxillary artery (branch of external loops around 3rd carotid). 1st arch is maximal. Internal product of 4th arch carotid artery (subclavian artery) 4th Stapedial artery and hyoid artery. Second = stapedial. Common Left recurrent 6th carotid laryngeal nerve Common carotid artery and proximal part artery loops around of internal carotid artery. C is 3rd letter of product of 6th arch alphabet. (ductus arteriosus) On left, aortic arch; on right, proximal part of 3rd right subclavian artery. 4th arch (4 limbs) = 4th systemic. 6th Proximal part of pulmonary arteries and (on left only) ductus arteriosus. 6th arch = pulmonary and the pulmonary-to-systemic shunt (ductus arteriosus). uploaded by medbooksvn","286 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Embryology Heart embryology EMBRYONIC STRUCTURE GIVES RISE TO Truncus arteriosus Ascending aorta and pulmonary trunk Bulbus cordis Smooth parts (outflow tract) of left and right Primitive ventricle ventricles Primitive atrium Trabeculated part of left and right ventricles Left horn of sinus venosus Trabeculated part of left and right atria Right horn of sinus venosus Coronary sinus Endocardial cushion Smooth part of right atrium (sinus venarum) Atrial septum, membranous interventricular Right common cardinal vein and right anterior cardinal vein septum; AV and semilunar valves Superior vena cava (SVC) Posterior cardinal, subcardinal, and supracardinal veins Inferior vena cava (IVC) Primitive pulmonary vein Smooth part of left atrium First aortic Pericardium SVC Aortic arch arch Aortic roots Truncus Primitive Ascending aorta arteriosus left atrium Bulbus Pulmonary trunk cordis Right Left atrium atrium Sinus horn Ventricle Cardinal Atrium veins Sinus venosus Left ventricle Ventricles 22 days 24 days 35 days 50 days","Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Embryology SEC TION III 287 Fetal circulation LA 3 Ductus Blood in umbilical vein has a Po2 of \u2248 30 mm\u00a0Hg arteriosus and is \u2248 80% saturated with O2. Umbilical Superior vena cava RA arteries have low O2 saturation. 2 Foramen ovale RV LV Pulmonary artery 3 important shunts: Portal vein 1 Ductus \u0007Blood entering fetus through the venosus umbilical vein is conducted via the ductus venosus into the IVC, bypassing hepatic Aorta circulation. Inferior vena cava \u0007Most of the highly oxygenated blood Umbilical vein Umbilical Internal iliac artery reaching the heart via the IVC is directed To placenta arteries through the foramen ovale into the left High O2 From placenta Moderate O2 atrium. Low O2 Deoxygenated blood from the SVC passes Very low O2 through the RA \u008e\u00a0RV \u008e main pulmonary artery \u008e\u00a0ductus arteriosus \u008e\u00a0descending aorta; shunt is due to high fetal pulmonary artery resistance. At birth, infant takes a breath \u008e\u00a0\u0090\u00a0resistance in pulmonary vasculature \u008e\u00a0\u008f left atrial pressure vs right atrial pressure\u008e\u00a0foramen ovale closes (now called fossa ovalis); \u008f in O2 (from respiration) and \u0090 in prostaglandins (from placental separation) \u008e closure of ductus arteriosus. NSAIDs (eg, indomethacin, ibuprofen) or acetaminophen help close the patent ductus arteriosus \u008e\u00a0ligamentum arteriosum (remnant of ductus arteriosus). \u201cEndomethacin\u201d ends the PDA. Prostaglandins E1 and E2 kEEp PDA open. Fetal-postnatal derivatives FETAL STRUCTURE POSTNATAL DERIVATIVE NOTES Ductus arteriosus Ligamentum arteriosum Near the left recurrent laryngeal nerve Ductus venosus Ligamentum venosum Urachus is part of allantois between bladder and umbilicus Foramen ovale Fossa ovalis Contained in falciform ligament Allantois \u008e urachus Median umbilical ligament Umbilical arteries Medial umbilical ligaments Umbilical vein Ligamentum teres hepatis (round ligament) uploaded by medbooksvn","288 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Anatomy ` \u2009C A R D I O VA S C UL A R \u2014 A N AT O M Y Heart anatomy LA is the most posterior part of the heart A \u200a; B Aortic knob A enlargement of the LA (eg, in mitral stenosis) Pulmonary artery can lead to compression of the esophagus SVC RV (dysphagia) and\/or the left recurrent laryngeal Azygos vein RA LA RA LV nerve, a branch of the vagus nerve, causing Descending aorta hoarseness (Ortner syndrome). IVC LA LV pv RV is the most anterior part of the heart and RV most commonly injured in trauma. LV is Ao about 2\/3 and RV is about 1\/3 of the inferior (diaphragmatic) cardiac surface B . Pericardium Consists of 3 layers (from outer to inner): Fibrous pericardium Coronary blood \u0083\t Fibrous pericardium Parietal pericardium supply \u0083\t Parietal pericardium Pericardial space \u0083\t Epicardium (visceral pericardium) Epicardium Pericardial space lies between parietal (visceral pericardium) pericardium and epicardium. Coronary vessels Pericardium innervated by phrenic nerve. Pericarditis can cause referred pain to the neck, Myocardium arms, or one or both shoulders (often left). Endocardium LAD and its branches supply anterior 2\/3 of Dominance: interventricular septum, anterolateral papillary \u0083\t Right-dominant circulation (most common) muscle, and anterior surface of LV. Most = PDA arises from RCA commonly occluded. \u0083\t Left-dominant circulation = PDA arises from LCX PDA supplies posterior 1\/3 of interventricular \u0083\t Codominant circulation = PDA arises from septum, posterior 2\/3 walls of ventricles, and both LCX and RCA posteromedial papillary muscle. Coronary blood flow to LV and interventricular RCA supplies AV node and SA node. Infarct septum peaks in early diastole. may cause nodal dysfunction (bradycardia or heart block). Right (acute) marginal artery Coronary sinus runs in the left AV groove and supplies RV. drains into the RA. PV LCA (or LM) PV SVC LA LCX LA RA OMA RCA Aorta IVC SVC LAD Key: RV AMA = Acute marginal artery PT PDA LAD = Left anterior descending artery RA LCA Posterior view (or LM) = Left (main) coronary artery LV LV LCX = Left circum\ufb02ex artery OMA = Obtuse marginal artery IVC RV PDA = Posterior descending artery PT = Pulmonary trunk AMA PV = Pulmonary vein Anterior view RCA = Right coronary artery","C ardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology SEC TION III 289 ` \u2009C A R D I O VA S C UL A R \u2014 P H Y S I O LO G Y Cardiac output variables Stroke volume Stroke Volume affected by Contractility, SV CAP. Afterload, and Preload. Stroke work (SW) is work done by ventricle to \u008f SV with: eject SV. \u0083\t \u008f\u00a0Contractility (eg, anxiety, exercise) SW \u221d SV \u00d7 MAP \u0083\t \u008f Preload (eg, early pregnancy) A failing heart has \u0090 SV (systolic and\/or diastolic \u0083\t \u0090 Afterload dysfunction). Contractility Contractility (and SV) \u008f with: Contractility (and SV) \u0090 with: \u0083\t Catecholamine stimulation via \u03b21 receptor: \u0083\t \u03b21-blockade (\u0090 cAMP) \u0083\t Activated protein kinase A \u0083\t Heart failure (HF) with systolic dysfunction \u0083\t Acidosis \u008e\u00a0phospholamban phosphorylation \u0083\t Hypoxia\/hypercapnia (\u0090 Po2\/\u200a\u008f Pco2) \u008e\u00a0active Ca2+ ATPase \u008e\u00a0\u008f\u00a0Ca2+ storage \u0083\t Nondihydropyridine Ca2+ channel blockers in sarcoplasmic reticulum \u0083\t Activated protein kinase A \u008e\u00a0Ca2+ channel phosphorylation \u008e\u00a0\u008f\u00a0Ca2+ entry \u008e\u00a0\u008f\u00a0Ca2+-induced Ca2+ release \u0083\t \u008f intracellular Ca2+ \u0083\t \u0090 extracellular Na+ (\u0090 activity of Na+\/Ca2+ exchanger) \u0083\t Digoxin (blocks Na+\/K+ pump \u008e \u008f intracellular Na+ \u008e \u0090 Na+\/Ca2+ exchanger activity \u008e \u008f intracellular Ca2+) Preload Preload approximated by ventricular end- Venous vasodilators (eg, nitroglycerin) \u0090\u00a0preload. diastolic volume (EDV); depends on venous tone and circulating blood volume. Afterload Afterload approximated by MAP. Arterial vasodilators (eg, hydralazine) \u008f\u00a0wall tension per Laplace\u2019s law \u008e\u00a0\u008f\u00a0pressure \u0090\u00a0afterload. \u008e\u00a0\u008f\u00a0afterload. ACE inhibitors and ARBs \u0090 both preload and afterload. LV compensates for \u008f afterload by thickening (hypertrophy) in order to \u0090 wall stress. Chronic hypertension (\u008f MAP) \u008e LV hypertrophy. Myocardial O2 demand is \u008f by: Cardiac oxygen \u0083\t \u008f contractility Wall tension follows Laplace\u2019s law: demand \u0083\t \u008f afterload (proportional to arterial pressure) \u0083\t \u008f heart rate Wall tension = pressure \u00d7 radius \u0083\t \u008f diameter of ventricle (\u008f wall tension) W\tall stress = pressure \u00d7 radius Coronary sinus contains most deoxygenated 2 \u00d7 wall thickness blood in body. uploaded by medbooksvn","290 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology Cardiac output equations EQUATION NOTES Stroke volume SV = EDV \u2212 ESV ESV = end-systolic volume. Ejection fraction E\tF = \u2002ESDVV\u2002\t= EDVED\u2212 VESV EF is an index of ventricular contractility (\u0090 in Cardiac output CO = Q\u02d9 = SV \u00d7 HR systolic HF; usually normal in diastolic HF). Fick principle: In early stages of exercise, CO maintained by \u008f\u00a0HR and \u008f SV. In later stages, CO maintained C\tO = (arterial rate of O2 consumption content) by \u008f HR only (SV plateaus). O2 content \u2013 venous O2 Diastole is shortened with \u008f\u008f HR (eg, ventricular Pulse pressure PP = systolic blood pressure (SBP) \u2013 diastolic tachycardia) \u008e \u0090 diastolic filling time \u008e \u0090 SV blood pressure (DBP) \u008e \u0090 CO. Mean arterial pressure MAP = CO \u00d7 total peripheral resistance (TPR) PP directly proportional to SV and inversely proportional to arterial compliance. \u008f PP in aortic regurgitation, aortic stiffening (isolated systolic hypertension in older adults), obstructive sleep apnea (\u008f\u00a0sympathetic tone), high-output state (eg, anemia, hyperthyroidism), exercise (transient). \u0090 PP in aortic stenosis, cardiogenic shock, cardiac tamponade, advanced HF. MAP (at resting HR) = 2\/3 DBP + 1\/3 SBP = DBP + 1\/3 PP. Starling curves Normal (exercise) Force of contraction is proportional to end- Normal (rest) diastolic length of cardiac muscle fiber Stroke volume (CO) Running Heart failure + (preload). Walking positive inotrope Rest \u008f contractility with catecholamines, positive Myocardial contractility inotropes (eg, dobutamine, milrinone, Heart failure digoxin). Ventricular EDV (preload) \u0090 contractility with loss of functional myocardium (eg, MI), \u03b2-blockers (acutely), nondihydropyridine Ca2+ channel blockers, HF.","C ardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology SEC TION III 291 Resistance, pressure, Volumetric flow rate ( ) = flow velocity (v) \u00d7 Q \u221d r4 flow R \u221d 1\/r4 cross-sectional area (A) Capillaries have highest total cross-sectional Resistance area and lowest flow velocity. Pressure gradient drives flow from high pressure \tTTR=ToRo\tRoTttdT=atTa=alrRll=irRev\u2081rre\u2081sie+Rnis+ssi1RitgsRas\u2082t+tanp\u2082+anc+rRnReceQRc\u20832esoes\u2083\t.+of.u..vf.o.rRevfese3vs(see.\u0394slse.sPsl.ies)nli=snseis8rnei\u03b7erssiee:(svr:iiescs:osit\u03c0y)r4\u00d7 length to low pressure. R\u2081 R\u2082 R\u2083 Arterioles account for most of TPR. Veins R\u2081 R\u2082 R\u2083 provide most of blood storage capacity. TToottaallrerseisitastnacnecoef voefsvselsssienlspainralplealr: allel: Viscosity depends mostly on hematocrit. \t\u2014R1T\u2014R1T\u2009\u2009o\u2009RT\u2009=1t=Ta\u2009\u2014R\u20061\u2009l\u2014R\t1\u2081=r\u2081e+\u2009+s\u2009\u2014R\u2009R\u200ai11s\u2014R\u208211\u200at\u2009\t\u2082+a++n\u2014R1c\u2014RR\u2083\u20091\u200ae1\u2083..2\u200a\u2009o.\t..+.f vRe\u2009\u200a1s3\u200a\u2009se. l.s.in parallel: Viscosity \u008f in hyperproteinemic states (eg, R\u2081 multiple myeloma), polycythemia. R\u2081 Viscosity \u0090 in anemia. R\u2082 R\u2082 R\u2083 R\u2083 Cardiac and vascular function curves inotropy \u2193 \u2193 volume, venous tone \u2193TPR Cardiac output\/venous returnNormalCardiac function curve Cardiac output\/venous return\u2193inotropy Cardiac output\/venous return Mean Vascular function curve \u2193volume, \u2193 TPR systemic venous tone C RAP pressure B RAP A RAP Intersection of curves = operating point of heart (ie, venous return and CO are equal, as circulatory system is a closed system). GRAPH EFFECT EXAMPLES Inotropy Changes in contractility \u008e altered SV \u008e altered Catecholamines, dobutamine, milrinone, CO\/VR and RA pressure (RAP) digoxin, exercise \u2295 \u0007HF with reduced EF, narcotic overdose, sympathetic inhibition \u229d Venous return Changes in circulating volume \u008e altered RAP Fluid infusion, sympathetic activity, \u008e altered SV \u008e change in CO arteriovenous shunt \u2295 Acute hemorrhage, spinal anesthesia \u229d T\u0007 otal peripheral Changes in TPR \u008e\u00a0altered CO Vasopressors \u2295 resistance Change in RAP unpredictable Exercise, arteriovenous shunt \u229d Changes often occur in tandem, and may be reinforcing (eg, exercise \u008f inotropy and \u0090 TPR to maximize CO) or compensatory (eg, HF \u0090 inotropy \u008e fluid retention to \u008f preload to maintain CO). uploaded by medbooksvn","292 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology Pressure-volume loops and cardiac cycle The black loop represents normal cardiac physiology. 140 Contractility Afterload Aortic pressure Phases\u2014left ventricle: 120 SV SV I\u0007 sovolumetric contraction\u2014period ESV between mitral valve closing and aortic Left ventricular pressure (mm Hg) EF S2 valve opening; period of highest O2 ESV Preload consumption SV \u0007Systolic ejection\u2014period between aortic 100 Aortic valve opening and closing valve \u0007Isovolumetric relaxation\u2014period between 80 closes Aortic aortic valve closing and mitral valve valve opening Stroke opens \u0007Rapid filling\u2014period just after mitral volume valve opening 60 (EDV-ESV) R\u0007 educed filling\u2014period just before mitral valve closing 40 Mitral Mitral valve valve Heart sounds: closes S1\u2014mitral and tricuspid valve closure. Loudest opens 20 & at mitral area. S3 S4 S1 S2\u2014aortic and pulmonary valve closure. ESV Left ventricular volume EDV Loudest at left upper sternal border. S3\u2014in early diastole during rapid ventricular Ventricular systole Ventricular diastole filling phase. Best heard at apex with patient Pressure (mm Hg)120 in left lateral decubitus position. Associated Atrial100 with \u008f filling pressures (eg, MR, AR, HF, systole80 thyrotoxicosis) and more common in dilated Isovolumetric60 ventricles (but can be normal in children, contraction40 young adults, athletes, and pregnancy). Rapid20 Turbulence caused by blood from LA mixing ejection with \u008f\u00a0ESV. Reduced0 S4\u2014in late diastole (\u201catrial kick\u201d). Turbulence ejection caused by blood entering stiffened LV. Best IsovolumetricHeart heard at apex with patient in left lateral relaxationsounds decubitus position. High atrial pressure. RapidVentricular Associated with ventricular noncompliance (eg, \ufb01llingvolume hypertrophy). Considered abnormal if palpable. Reduced Common in older adults. \ufb01lling Aortic Aortic valve closes Aortic Jugular venous pulse (JVP): valve Dicrotic notch pressure a wave\u2014atrial contraction. Prominent in AV opens dissociation (cannon a wave), absent in atrial Mitral c Left atrial pressure Left ventricular fibrillation. valve x pressure c wave\u2014RV contraction (closed tricuspid valve closes bulging into atrium). v Mitral valve opens x descent\u2014atrial relaxation and downward a y displacement of closed tricuspid valve during rapid ventricular ejection phase. Reduced or S4 S1 S2 S3 absent in tricuspid regurgitation and right HF because pressure gradients are reduced. Right a c vy v wave\u2014\u008f RA pressure due to \u008f\u00a0volume against atrial x closed tricuspid valve. pressure R y descent\u2014RA emptying into RV. Prominent curve P T P in constrictive pericarditis, absent in cardiac (JVP) Q tamponade. S ECG 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Time (sec)","C ardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology SEC TION III 293 Pressure-volume loops and valvular disease Aortic stenosis 200 LV > aortic \u008f\u00a0LV pressure 120 pressure \u008f\u00a0ESV LV pressure (mm Hg) 100 Blood pressure (mm Hg) No change in EDV (if mild) 50 \u0090\u00a0SV 0 100 200 0 Ventricular hypertrophy \u008e\u00a0\u0090\u00a0ventricular LV volume (ml) Time (RR interval) compliance \u008e\u00a0\u008f\u00a0EDP for given EDV Aortic regurgitation 200 No true isovolumetric phase \u008f\u00a0EDV LV pressure (mm Hg) 100 Blood pressure (mm Hg) 120 Large \u008f\u00a0SV pulse Loss of dicrotic notch 0 100 200 pressure \u008f\u00a0LA pressure LV volume (ml) 50 \u0090\u00a0EDV because of impaired ventricular 0 filling Time (RR interval) \u0090\u00a0ESV \u0090\u00a0SV Mitral stenosis 200 No true isovolumetric phase LV pressure (mm Hg) 100 Blood pressure (mm Hg) 120 \u0090\u00a0ESV due to \u0090\u00a0resistance and 0 100 200 LA > LV \u008f\u00a0regurgitation into LA during systole 50 pressure \u008f\u00a0EDV due to \u008f\u00a0LA volume\/pressure from LV volume (ml) 0 regurgitation \u008e\u00a0\u008f\u00a0ventricular filling Time (RR interval) \u008f\u00a0SV (forward flow into systemic circulation Mitral regurgitation 200 plus backflow into LA) LV pressure (mm Hg) Blood pressure (mm Hg) 120 100 Tall V-wave 50 0 100 200 0 Time (RR interval) LV volume (ml) uploaded by medbooksvn","294 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology Splitting of S2 Inspiration \u008e drop in intrathoracic pressure E Physiologic splitting \u008e\u00a0\u008f\u00a0venous return \u008e\u00a0\u008f RV filling \u008e\u00a0\u008f\u00a0RV S1 A2 P2 stroke volume \u008e\u00a0\u008f\u00a0RV ejection time Wide splitting \u008e\u00a0delayed closure of pulmonic valve. I Fixed splitting \u0090\u00a0pulmonary impedance (\u008f capacity of the Normal delay Paradoxical splitting pulmonary circulation) also occurs during inspiration, which contributes to delayed E = Expiration closure of pulmonic valve. I = Inspiration Seen in conditions that delay RV emptying (eg, E pulmonic stenosis, right bundle branch block). S1 A2 P2 Causes delayed pulmonic sound (especially on inspiration). An exaggeration of normal I splitting. Abnormal delay Heard in ASD. ASD \u008e\u00a0left-to-right shunt E = \u008e\u00a0\u008f\u00a0RA and RV volumes \u008e\u00a0\u008f\u00a0flow through S1 A2 P2 pulmonic valve \u008e\u00a0delayed pulmonic valve closure (independent of respiration). I = Heard in conditions that delay aortic valve E P2 A2 closure (eg, aortic stenosis, left bundle branch S1 block). Normal order of semilunar valve closure is reversed: in paradoxical splitting P2 I occurs before A2. On inspiration, P2 closes later and moves closer to A2, \u201cparadoxically\u201d eliminating the split. On expiration, the split can be heard (opposite to physiologic splitting).","C ardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology SEC TION III 295 Auscultation of the heart Where to listen: APT M 1 Aortic stenosis P Pulmonic area: 2 A Aortic area: 3 P Systolic ejection murmur 4 T Pulmonic stenosis Systolic murmur 5 Atrial septal defect Aortic stenosis 6 M Flow murmur Flow murmur 7 (eg, physiologic murmur) A M Mitral area (apex): Aortic valve sclerosis Mitral Systolic murmur T Tricuspid area: regurgitation Mitral regurgitation Mitral valve prolapse Holosystolic murmur Tricuspid regurgitation Diastolic murmur Ventricular septal defect Mitral stenosis Diastolic murmur Left sternal border: Tricuspid stenosis Systolic murmur Aortic Hypertrophic Pulmonic cardiomyopathy Tricuspid Diastolic murmur Mitral Aortic regurgitation Pulmonic regurgitation MANEUVER CARDIOVASCULAR CHANGES MURMURS THAT INCREASE WITH MANEUVER MURMURS THAT DECREASE WITH MANEUVER Standing, Valsalva \u0090 preload (\u0090 LV volume) MVP (\u0090 LV volume) with Most murmurs (\u0090 flow through (strain phase) earlier midsystolic click stenotic or regurgitant valve) \u008f preload (\u008f LV volume) Passive leg raise \u008f preload, \u008f afterload (\u008f LV HCM (\u0090 LV volume) MVP (\u008f LV volume) with later Squatting midsystolic click volume) Most murmurs (\u008f flow through Hand grip \u008f\u008f afterload \u008e \u008f reverse flow stenotic or regurgitant valve) HCM (\u008f LV volume) Inspiration across aortic valve (\u008f LV Most other left-sided murmurs AS (\u0090 transaortic valve pressure volume) (AR, MR, VSD) gradient) \u008f venous return to right heart, \u0090\u00a0venous return to left heart Most right-sided murmurs HCM (\u008f LV volume) Most left-sided murmurs uploaded by medbooksvn","296 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology Heart murmurs AUSCULTATION CLINICAL ASSOCIATIONS NOTES SyS1stolic S2 Crescendo-decrescendo In older (>60 years old) patients, Can lead to Syncope, Aortic stenosis S2 ejection murmur, loudest most commonly due to age- Angina, Dyspnea on at heart base, radiates to related calcification exertion (SAD) S1 carotids In younger patients, most LV pressure > aortic S1 S2 Soft S2 +\/\u2013 ejection click commonly due to early-onset pressure during \u201cPulsus parvus et tardus\u201d\u2014 calcification of bicuspid aortic systole MSS11itral\/tricuMCspid reSS22gurgitation valve weak pulses with delayed peak MC due to sudden S1 S2 MR: often due to ischemic heart tensing of chordae S1 Holosystolic, high-pitched disease (post-MI), MVP, LV tendineae as mitral S1 SS22 \u201cblowing\u201d murmur dilatation, rheumatic fever leaflets prolapse into LA (chordae cause S1 MR: loudest at apex, radiates TR: often due to RV dilatation crescendo with click) S1 S2 toward axilla Either MR or TR: infective S1 S2 OS Larger VSDs have TR: loudest at tricuspid area endocarditis lower intensity Mitral valve prolapse murmur than Late crescendo murmur with Usually benign, but can smaller VSDs S1 S2 midsystolic click (MC) that predispose to infective S1 MC S2 occurs after carotid pulse endocarditis Hyperdynamic pulse S1 S2 and head bobbing Best heard over apex Can be caused by rheumatic when severe and SSS111 MC SSS222 Loudest just before S2 fever, chordae rupture, or chronic S1 S2 myxomatous degeneration (1\u00b0 or Holosystolic, harsh-sounding 2\u00b0 to connective tissue disease) Can progress to left SS11 murmur HF S1 SSS222 Congenital Loudest at tricuspid area OS due to abrupt halt VSe1ntricular septalS2dOeSfect\u2008 in leaflet motion in diastole after rapid S1SS11 S2SS22 opening due to S1 S2 OS fusion at leaflet tips S1 S2 LA >> LV pressure DS1SSSi111astolic MMCC S2SS22 during diastole S2 You need a patent for Aortic regurgitation Early diastolic, decrescendo, Causes include BEAR: that machine. high-pitched \u201cblowing\u201d \u0083\t Bicuspid aortic valve S1SSS111 SSS2S222 murmur best heard at base \u0083\t Endocarditis (aortic root dilation) or left \u0083\t Aortic root dilation S1SSS111 MC S2SSS222 OOSS sternal border (valvular \u0083\t Rheumatic fever disease) S1SSS111 S2SSS222 Wide pulse pressure, pistol shot Follows opening snap (OS) femoral pulse, pulsing nail bed Mitral stenosis Delayed rumbling mid-to-late (Quincke pulse) S1S1 MC S2S2OS murmur (\u0090 interval between Late and highly specific sequelae S2 and OS correlates with \u008f of rheumatic fever S1S1 SS22 severity) Chronic MS can result in S1 S2 OS LA dilation and pulmonary congestion, atrial fibrillation, Continuous Ortner syndrome, hemoptysis, right HF Patent ductus arteriosus Continuous machinelike Often due to congenital rubella murmur, best heard at left or prematurity S1 S2 infraclavicular area Loudest at S2","C ardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology SEC TION III 297 Myocardial action Phase 0 = rapid upstroke and depolarization\u2014 Phase 1 ( IK) potential voltage-gated Na+ channels open. Phase 2 (ICa and IK) Pacemaker action Phase 1 = initial repolarization\u2014inactivation of 0 mV 200 msec Phase 3 (IK) potential voltage-gated Na+ channels. Voltage-gated K+ Phase 0 K+ K+ E ective refractory period channels begin to open. (INa) Phase 4 (dominated by IK) Phase 2 = plateau (\u201cplatwo\u201d)\u2014Ca2+ influx \u201385 mV K+ through voltage-gated Ca2+ channels balances Extracellular K+ efflux. Ca2+ influx triggers Ca2+ release Intracellular from sarcoplasmic reticulum and myocyte Na+ Ca2+ contraction (excitation-contraction coupling). Myocyte Phase 3 = rapid repolarization\u2014massive K+ Occurs in all cardiac myocytes except for those efflux due to opening of voltage-gated slow in the SA and AV nodes. delayed-rectifier K+ channels and closure of voltage-gated Ca2+ channels. Phase 4 = resting potential\u2014high K+ permeability through K+ channels. In contrast to skeletal muscle: \u0083\t Cardiac muscle action potential has a plateau due to Ca2+ influx and K+ efflux. \u0083\t Cardiac muscle contraction requires Ca2+ influx from ECF to induce Ca2+ release from sarcoplasmic reticulum (Ca2+-induced Ca2+ release). \u0083\t Cardiac myocytes are electrically coupled to each other by gap junctions. Occurs in the SA and AV nodes. Key differences from the ventricular action potential include: Phase 0 = upstroke\u2014opening of voltage-gated Ca2+ channels. Fast voltage-gated Na+ channels are permanently inactivated because of the less negative resting potential of these cells. Results in a slow conduction velocity that is used by the AV node to prolong transmission from the atria to ventricles. Phases 1 and 2 are absent. Phase 3 = repolarization\u2014inactivation of the Ca2+ channels and \u008f activation of K+ channels \u008e \u008f K+ efflux. Phase 4 = slow spontaneous diastolic depolarization due to If (\u201cfunny current\u201d). If channels responsible for a slow, mixed Na+ inward\/K+ outward current; different from INa in phase 0 of ventricular action potential. Accounts for automaticity of SA and AV nodes. The slope of phase 4 in the SA node determines HR. ACh\/adenosine \u0090 the rate of diastolic depolarization and \u0090 HR, while catecholamines \u008f\u00a0depolarization and \u008f HR. Sympathetic stimulation \u008f the chance that If channels are open and thus \u008f HR. 0 Membrane potential (mV) \u201320 ICa(L-type) IK Phase 0 Phase 3 \u201340 Threshold Time (ms) Phase 4 \u201360 If (Na+ and K+) \u201380 and ICa(T-type) uploaded by medbooksvn","298 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology Electrocardiogram Conduction pathway: SA node \u008e\u00a0atria P wave\u2014atrial depolarization. \u008e\u00a0AV\u00a0node \u008e\u00a0bundle of His \u008e\u00a0right and PR interval\u2014time from start of atrial left bundle branches \u008e\u00a0Purkinje fibers \u008e\u00a0ventricles; left bundle branch divides into depolarization to start of ventricular left anterior and posterior fascicles. depolarization (normally 120-200 msec). QRS complex\u2014ventricular depolarization SA node\u2014located in upper part of crista (normally < 100 msec). terminalis near SVC opening; \u201cpacemaker\u201d QT interval\u2014ventricular depolarization, inherent dominance with slow phase of mechanical contraction of the ventricles, upstroke. ventricular repolarization. T wave\u2014ventricular repolarization. T-wave AV node\u2014located in interatrial septum near inversion may indicate ischemia or recent MI. coronary sinus opening. Blood supply usually J point\u2014junction between end of QRS complex from RCA. 100-msec delay allows time for and start of ST segment. ventricular filling. ST segment\u2014isoelectric, ventricles depolarized. U wave\u2014prominent in hypokalemia (think Pacemaker rates: SA > AV > bundle of His\/ hyp\u201cU\u201dkalemia), bradycardia. Purkinje\/ventricles. Speed of conduction: His-Purkinje > Atria > Ventricles > AV node. He Parks At Ventura AVenue. 5 mm +1.0 0.2 seconds Aorta Aorta R Superior vena cava Superior P-R S-T vena cava segment segment Bachmann +0.5 Sinoatrial SA node bundle P J point T 0 mV (SA) node \u20130.5 Bachmann U AV node bundle Atrioventricular LberaftnbcuhndLbleeraftnbcuhndle P-R Q Q-T interval interval S (AV) nodeBundle of His Lfaesfct iacnleterLioerft anterior Coronary sinus fascicle QRS interval ori\ufb01ce Left posterior fascicle Left posterior Atrial Ventricular Ventricular Right bundle Purkinje \ufb01fbasecriscle depolarization depolarization repolarization Bundle of His branch Right bundlPeurkinje \ufb01bers branch","C ardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology SEC TION III 299 Atrial natriuretic Released from atrial myocytes in response to \u008f blood volume and atrial pressure. Acts via cGMP. peptide Causes vasodilation and \u0090 Na+ reabsorption at the renal collecting tubule. Dilates afferent renal arterioles and constricts efferent arterioles, promoting diuresis and contributing to \u201caldosterone escape\u201d mechanism. B-type (brain) Released from ventricular myocytes in response to \u008f tension. Similar physiologic action to ANP, natriuretic peptide with longer half-life. BNP blood test used for diagnosing HF (very good negative predictive value). Baroreceptors and chemoreceptors Receptors: AFFERENT EFFERENT \u0083\t Aortic arch transmits via vagus nerve to solitary nucleus of Solitary nucleus medulla (responds to changes in BP). IX: Medulla Sympathetic \u0083\t Carotid sinus (dilated region superior to bifurcation of carotid Glossopharyngeal X: chain arteries) transmits via glossopharyngeal nerve to solitary nucleus Vagus of medulla (responds to changes in BP). nerve nerve Parasympathetic vagus nerve Chemoreceptors: Spinal cord Sympathetic \u0083\t Peripheral\u2014carotid and aortic bodies are stimulated by \u008f\u00a0Pco2, nerves \u0090\u00a0pH of blood, and \u0090\u00a0Po2 (<\u00a060 mm\u00a0Hg). Carotid sinus baroreceptor \u0083\t Central\u2014are stimulated by changes in pH and Pco2 of brain Carotid body interstitial fluid, which in turn are influenced by arterial CO2 as chemoreceptor H+ cannot cross the blood-brain barrier. Do not directly respond to Po2. Central chemoreceptors become less responsive with Aortic Blood chronically \u008f\u00a0Pco2 (eg, COPD) \u008e\u00a0\u008f\u00a0dependence on peripheral chemoreceptor vessels chemoreceptors to detect \u0090\u00a0O2 to drive respiration. Aortic Baroreceptors: baroreceptor \u0083\t Hypotension\u2014\u0090 arterial pressure \u008e\u00a0\u0090\u00a0stretch \u008e \u0090 afferent SA node baroreceptor firing \u008e \u008f efferent sympathetic firing and \u0090\u00a0efferent AV node parasympathetic stimulation \u008e\u00a0vasoconstriction, \u008f\u00a0HR, \u008f contractility, \u008f\u00a0BP. Important in the response to hypovolemic shock. \u0083\t Carotid massage\u2014\u008f carotid sinus pressure \u008e \u008f afferent baroreceptor firing \u008e \u008f AV node refractory period \u008e \u0090 HR \u008e \u0090 CO. Also leads to peripheral vasodilation. Can cause presyncope\/syncope. Exaggerated in underlying atherosclerosis, prior neck surgery, older age. \u0083\t Component of Cushing reflex (triad of hypertension, bradycardia, and respiratory depression)\u2014\u008f intracranial pressure constricts arterioles \u008e cerebral ischemia \u008e\u00a0\u008f\u00a0pCO2 and \u0090\u00a0pH \u008e\u00a0central reflex sympathetic \u008f\u00a0in perfusion pressure (hypertension) \u008e \u008f stretch \u008e peripheral reflex baroreceptor\u2013 induced bradycardia. uploaded by medbooksvn","300 SEC TION III Cardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology Normal resting cardiac Pulmonary capillary wedge pressure (PCWP; 120\/80 4 12 PCWP pressures in mm Hg) is a good approximation of left 25\/8 atrial pressure, except in mitral stenosis when PCWP > LV end diastolic pressure. PCWP <12 is measured with pulmonary artery catheter (Swan-Ganz catheter). <5 120\/<12 25\/<5 Autoregulation How blood flow to an organ remains constant over a wide range of perfusion pressures. ORGAN FACTORS DETERMINING AUTOREGULATION Lungs Hypoxia causes vasoconstriction The pulmonary vasculature is unique in that Heart alveolar hypoxia causes vasoconstriction so Brain Local metabolites (vasodilatory): NO, CO2, \u0090\u00a0O2 that only well-ventilated areas are perfused. In Kidneys other organs, hypoxia causes vasodilation Local metabolites (vasodilatory): CO2 (pH) Skeletal muscle Myogenic (stretch-dependent response of \u00adSkin afferent arteriole) and tubuloglomerular feedback Local metabolites during exercise (vasodilatory): CHALK CO2, H+, Adenosine, Lactate, K+ At rest: sympathetic tone in arteries Sympathetic vasoconstriction most important mechanism for temperature control","C ardiovascular\u2003 \uf07d\u2009cardiovascular\u2014Physiology SEC TION III 301 Capillary fluid Starling forces determine fluid movement through capillary membranes: exchange \u0083\t Pc = capillary hydrostatic pressure\u2014pushes fluid out of capillary \u0083\t Pi = interstitial hydrostatic pressure\u2014pushes fluid into capillary \u0083\t \u03c0c = plasma oncotic pressure\u2014pulls fluid into capillary \u0083\t \u03c0i = interstitial fluid oncotic pressure\u2014pulls fluid out of capillary Jv = net fluid flow = Kf [(Pc \u2212 Pi) \u2212 \u03c3(\u03c0c \u2212 \u03c0i)] Kf = capillary permeability to fluid \u03c3 = reflection coefficient (measure of capillary impermeability to protein) Edema\u2014excess fluid outflow into interstitium commonly caused by: \u0083\t \u008f capillary pressure (\u008f Pc; eg, HF) \u0083\t \u008f capillary permeability (\u008f Kf\u2009; eg, toxins, infections, burns) \u0083\t \u008f interstitial fluid oncotic pressure (\u008f \u03c0i; eg, lymphatic blockage) \u0083\t \u0090 plasma proteins (\u0090 \u03c0c; eg, nephrotic syndrome, liver failure, protein malnutrition) Interstitium Filtration Reabsorption Net \ufb02ow into capillary Net \ufb02ow out of capillary Osmotic pressure Arteriole end Venous end of capillary of capillary Interstitium Hydrostatic pressure Net \ufb02uid \ufb02ow = Kf [ (Pc - Pi ) - \u03c3 (\u03c0c- \u03c0i) ] uploaded by medbooksvn","302 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology ` \u2009C A R D I O VA S C UL A R \u2014 PAT H O LO G Y Congenital heart diseases RIGHT-TO-LEFT SHUNTS Early cyanosis\u2014\u201cblue babies.\u201d Often diagnosed The 5 T\u2019s: prenatally or become evident immediately 1. Truncus arteriosus (1 vessel) after birth. Usually require urgent surgical 2. Transposition (2 switched vessels) treatment and\/or maintenance of a PDA. 3. Tricuspid atresia (3 = Tri) 4. Tetralogy of Fallot (4 = Tetra) 5. TAPVR (5 letters in the name) Persistent truncus Truncus arteriosus fails to divide into Aorta arteriosus pulmonary trunk and aorta due to failure of Pulmonary aorticopulmonary septum formation; most artery D-transposition of patients have accompanying VSD. great arteries Left A Aorta leaves RV (anterior) and pulmonary ventricle trunk leaves LV (posterior) \u008e separation of Tricuspid atresia systemic and pulmonary circulations A . Not Right Tetralogy of Fallot compatible with life unless a shunt is present ventricle B to allow mixing of blood (eg, VSD, PDA, or patent foramen ovale). PROVe. Squatting: \u008f SVR, \u0090 right-to-left shunt, improves Due to failure of the aorticopulmonary septum to spiral (narrow superior mediastinum causes \u201cegg cyanosis. on a string\u201d appearance on CXR). Associated with 22q11 syndromes. Without surgical intervention, most infants die Pulmonary Overriding within the first few months of life. stenosis aorta Ventricular Absence of tricuspid valve, hypoplastic RV; Right ventricular septal defect requires both ASD and VSD for viability. hypertrophy Caused by anterosuperior displacement of the infundibular septum. Most common cause of early childhood cyanosis. P\u0007 ulmonary infundibular stenosis (most important determinant for prognosis) R\u0007 ight ventricular hypertrophy (RVH)\u2014 boot\u2011shaped heart on CXR B O\u0007 verriding aorta V\u0007 SD Pulmonary stenosis forces right-to-left flow across VSD \u008e RVH, \u201ctet spells\u201d (often caused by crying, fever, and exercise due to exacerbation of RV outflow obstruction). Total anomalous Pulmonary veins drain into right heart Can be caused by lithium exposure in utero. pulmonary venous circulation (SVC, coronary sinus, etc); return associated with ASD and sometimes PDA to allow for right-to-left shunting to maintain CO. Ebstein anomaly Displacement of tricuspid valve leaflets downward into RV, artificially \u201catrializing\u201d the ventricle. Associated with tricuspid regurgitation, accessory conduction pathways, right-sided HF.","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 303 Congenital heart diseases (continued) LEFT-TO-RIGHT SHUNTS Acyanotic at presentation; cyanosis may occur Right-to-left shunts: early cyanosis. years later. Frequency: VSD > ASD > PDA. Left-to-right shunts: \u201clater\u201d cyanosis. O2 saturation \u008f\u00a0in RV and pulmonary artery. Ventricular septal Asymptomatic at birth, may manifest weeks defect later or remain asymptomatic throughout O2 saturation \u008f\u00a0in RA, RV, and pulmonary life. Most smaller defects self-resolve; larger artery. May lead to paradoxical emboli Atrial septal defect defects, if left surgically untreated, cause (systemic venous emboli use ASD to bypass C ASD \u008f\u00a0pulmonary blood flow and LV overload, lungs and become systemic arterial emboli). which may progress to HF. Associated with Down syndrome. Defect in interatrial septum C ; wide, fixed split S2. Ostium secundum defects most common PDA is normal in utero and normally closes only and usually an isolated finding; ostium after birth. primum defects rarer and usually occur with other cardiac anomalies. Symptoms Patent ductus range from none to HF. Distinct from patent arteriosus foramen ovale, which is due to failed fusion. Patent ductus In fetal period, shunt is right to left (normal). arteriosus In neonatal period, \u0090 pulmonary vascular resistance \u008e shunt becomes left to right D \u008e\u00a0progressive RVH and\/or LVH and HF. Associated with a continuous, \u201cmachinelike\u201d murmur. Patency is maintained by PGE synthesis and low O2 tension. Uncorrected PDA D can eventually result in late cyanosis in the lower extremities (differential cyanosis). Eisenmenger Right Left ventricle syndrome ventricle Left-to-right shunt Uncorrected left-to-right shunt (VSD, ASD, Right-to-left shunt PDA) \u008e \u008f pulmonary blood flow \u008e\u00a0pathologic (Eisenmenger syndrome) remodeling of vasculature \u008e\u00a0pulmonary arterial hypertension. RVH occurs to compensate \u008e shunt becomes right to left when RV > LV pressure (see illustration). Causes late cyanosis, clubbing, and polycythemia. Age of onset varies depending on size and severity of initial left-to-right shunt. uploaded by medbooksvn","304 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Coarctation of the Aortic narrowing A near insertion of ductus arteriosus (\u201cjuxtaductal\u201d). Associated with bicuspid aorta aortic valve, other heart defects, and Turner syndrome. Hypertension in upper extremities. Lower A extremities are cold with weak, delayed pulses (brachiofemoral delay). With age, intercostal arteries enlarge due to collateral circulation; arteries erode ribs \u008e\u00a0notched appearance on CXR. Coarct Complications include HF, \u008f\u00a0risk of cerebral hemorrhage (berry aneurysms), aortic rupture, and possible infective endocarditis. Persistent pulmonary Persistence of \u008f\u00a0pulmonary vascular resistance after birth. Associated with abnormal development hypertension of the and postpartum adaptation of pulmonary vasculature. Risk factors include aspiration of meconium- newborn stained amniotic fluid and neonatal pneumonia. Leads to right-to-left shunt through foramen ovale and ductus arteriosus. Newborn presents with signs of respiratory distress (eg, tachypnea) and cyanosis. Preductal O2 saturation is often higher than postductal. Equal pulses (no delay). Congenital cardiac ASSOCIATION DEFECT defect associations Prenatal alcohol exposure (fetal alcohol VSD, PDA, ASD, tetralogy of Fallot syndrome) PDA, pulmonary artery stenosis, septal defects Congenital rubella AV septal defect (endocardial cushion defect), Down syndrome VSD, ASD Infant of patient with diabetes during pregnancy Transposition of great arteries, truncus Marfan syndrome arteriosus, tricuspid atresia, VSD MVP, thoracic aortic aneurysm and dissection, Prenatal lithium exposure Turner syndrome aortic regurgitation Williams syndrome Ebstein anomaly 22q11 syndromes Bicuspid aortic valve, coarctation of aorta Supravalvular aortic stenosis Truncus arteriosus, tetralogy of Fallot Hypertension Persistent systolic BP \u2265 130 mm Hg and\/or diastolic BP \u2265 80 mm Hg. RISK FACTORS \u008f age, obesity, diabetes, physical inactivity, high-sodium diet, excess alcohol intake, tobacco FEATURES smoking, family history; incidence greatest in Black > White > Asian populations. A 90% of hypertension is 1\u00b0 (essential) and related to \u008f CO or \u008f TPR. Remaining 10% mostly 2\u00b0 PREDISPOSES TO to renal\/renovascular diseases such as fibromuscular dysplasia (characteristic \u201cstring of beads\u201d appearance of renal artery A , usually seen in adult females) and atherosclerotic renal artery stenosis, 1\u00b0 hyperaldosteronism, or obstructive sleep apnea. Hypertensive urgency\u2014severe (\u2265 180\/\u2265 120 mm\u00a0Hg) hypertension without acute end-organ damage. Hypertensive emergency\u2014formerly called malignant hypertension. Severe hypertension with evidence of acute end-organ damage (eg, encephalopathy, stroke, retinal hemorrhages and exudates, papilledema, MI, HF, aortic dissection, kidney injury, microangiopathic hemolytic anemia, eclampsia). Arterioles may show fibrinoid necrosis. CAD, LVH, HF, atrial fibrillation; aortic dissection, aortic aneurysm; stroke; CKD (hypertensive nephropathy); retinopathy.","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 305 Hyperlipidemia signs Plaques or nodules composed of lipid-laden histiocytes in skin A , especially the eyelids Xanthomas (xanthelasma B ). Tendinous xanthoma Lipid deposit in tendon C , especially Achilles tendon and finger extensors. Corneal arcus Lipid deposit in cornea. Common in older adults (arcus senilis D ), but appears earlier in life with hypercholesterolemia. ABCD Atherosclerosis Very common form of arteriosclerosis (hardening of arteries). Disease of elastic arteries and large- and medium-sized muscular arteries; caused by buildup of cholesterol plaques in tunica intima. LOCATION RISK FACTORS Abdominal aorta > coronary artery > popliteal artery > carotid artery > circle of Willis. SYMPTOMS A copy cat named Willis. PROGRESSION Modifiable: hypertension, tobacco smoking, dyslipidemia (\u008f\u00a0LDL, \u0090\u00a0HDL), diabetes. COMPLICATIONS Non-modifiable: age, male sex, postmenopausal status, family history. Normal artery Angina, claudication, but can be asymptomatic. Lumen Inflammation important in pathogenesis: endothelial cell dysfunction \u008e macrophage and LDL accumulation \u008e foam cell formation \u008e fatty streaks \u008e smooth muscle cell migration (involves PDGF and FGF), proliferation, and extracellular matrix deposition \u008e fibrous plaque \u008e complex atheromas A \u008e calcification (calcium content correlates with risk of complications). Ischemia, infarction, aneurysm formation, peripheral vascular disease, thrombosis, embolism. Endothelial Fatty streak Fibrous plaque dysfunction formation formation A Endothelium Monocyte LDL-laden Foam cell Smooth muscle Smooth macrophage Fatty streak migration muscle Smooth muscle Damaged endothelium Fibrous plaque uploaded by medbooksvn","306 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Cholesterol emboli Microembolization of cholesterol displaced from atherosclerotic plaques in large arteries (usually syndrome the aorta). Results in end-organ damage due to small artery emboli and an inflammatory response (eg, livedo reticularis, digital ischemia [blue toe syndrome], acute renal failure, cerebrovascular accident, gut ischemia). Pulses remain palpable because larger arteries are unaffected. May follow invasive vascular procedures (angiography, angioplasty, endovascular grafting). Arteriolosclerosis Common form of arteriosclerosis. Affects small A B arteries and arterioles. Two types: \u0083\t Hyaline\u2014vessel wall thickening 2\u00b0 to plasma protein leak into subendothelium in hypertension or diabetes mellitus A . \u0083\t Hyperplastic\u2014\u201conion skinning\u201d B in severe hypertension with proliferation of smooth muscle cells. Aortic aneurysm Localized pathologic dilation of the aorta. May cause abdominal and\/or back pain, which is a sign of leaking, dissection, or imminent rupture. Thoracic aortic aneurysm Associated with cystic medial degeneration. Risk factors include hypertension, bicuspid aortic valve, connective tissue disease (eg, Marfan syndrome). Also associated with 3\u00b0 syphilis (obliterative endarteritis of the vasa vasorum). Aortic root dilatation may lead to aortic valve regurgitation. Abdominal aortic Associated with transmural (all 3 layers) Fusiform aneurysm inflammation and extracellular matrix aneurysm A degradation. Risk factors include tobacco use, \u008f age, male sex, family history. May present as Ascending thoracic aorta Saccular Liver Sp palpable pulsatile abdominal mass (arrows in Aortic arch aneurysm A point to outer dilated aortic wall). Rupture Descending thoracic aorta may present as triad of pulsatile abdominal Abdominal aorta mass, acute abdominal\/back pain, and resistant hypotension. Most often infrarenal (distribution of vasa vasorum is reduced).","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 307 Traumatic aortic Due to trauma and\/or deceleration injury, most commonly at aortic isthmus (proximal descending rupture aorta just distal to origin of left subclavian artery). X-ray may reveal widened mediastinum. Aortic dissection Longitudinal intimal tear forming a false Stanford classi\ufb01cation Type B A lumen. Associated with hypertension (most important risk factor), bicuspid aortic valve, Type A Subclavian steal inherited connective tissue disorders (eg, syndrome Marfan syndrome). Can present with tearing, Ascending sudden-onset chest pain radiating to the back Descending +\/\u2212 markedly unequal BP in arms. CXR can show mediastinal widening. Can result in Type I Type II Type III organ ischemia, aortic rupture, death. DeBakey classi\ufb01cation Stanford type A (proximal): involves Ascending aorta (red arrow in A ). May extend to aortic arch or descending aorta (blue arrow in A ). May result in acute aortic regurgitation or cardiac tamponade. Treatment: surgery. Stanford type B (distal): involves only descending aorta (Below left subclavian artery). Treatment: \u03b2-blockers, then vasodilators. Stenosis of subclavian artery proximal to origin Right Left of vertebral artery \u008e\u00a0hypoperfusion distal to vertebral vertebral stenosis \u008e\u00a0reversed blood flow in ipsilateral artery vertebral artery \u008e\u00a0reduced cerebral perfusion artery on exertion of affected arm. Causes arm ischemia, pain, paresthesia, vertebrobasilar insufficiency (dizziness, vertigo). >15 mm Hg difference in systolic BP between arms. Associated with arteriosclerosis, Takayasu arteritis, heart surgery. Proximal left subclavian artery stenosis uploaded by medbooksvn","308 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Ischemic heart disease manifestations Angina Chest pain due to ischemic myocardium 2\u00b0 to coronary artery narrowing or spasm; no necrosis. \u0083\t Stable\u2014usually 2\u00b0 to atherosclerosis (\u2265 70% occlusion); exertional chest pain in classic distribution (possibly with ST depression on ECG), resolving with rest or nitroglycerin. \u0083\t Vasospastic (formerly Prinzmetal or variant)\u2014occurs at rest 2\u00b0 to coronary artery spasm; transient ST elevation on ECG. Tobacco smoking is a risk factor; hypertension and hypercholesterolemia are not. Triggers include cocaine, alcohol, and triptans. Treat with Ca2+ channel blockers, nitrates, and smoking cessation (if applicable). \u0083\t Unstable\u2014thrombosis with incomplete coronary artery occlusion; +\/\u2212 ST depression and\/or T-wave inversion on ECG but no cardiac biomarker elevation (unlike non\u2013ST-segment elevation MI [NSTEMI]); \u008f in frequency or intensity of chest pain or any chest pain at rest. Stable angina Unstable angina NSTEMI STEMI PAIN On exertion Mild exertion or at rest At rest At rest TROPONIN LEVEL No elevation No elevation Elevated Elevated INFARCTION None None RV LV RV LV Subendocardial Transmural ECG CHANGES None Possible ST depression ST depression and\/or ST elevation and\/or T-wave T-wave inversion Coronary steal inversion syndrome Distal to coronary stenosis, vessels are maximally dilated at baseline. Administration of vasodilators Sudden cardiac death (eg, dipyridamole, regadenoson) dilates normal vessels \u008e\u00a0blood is shunted toward well-perfused areas \u008e\u00a0ischemia in myocardium perfused by stenosed vessels. Principle behind pharmacologic Chronic ischemic stress tests with coronary vasodilators. heart disease Unexpected death due to cardiac causes within 1 hour of symptom onset, most commonly due Myocardial infarction to lethal arrhythmia (eg, ventricular fibrillation). Associated with CAD (up to 70% of cases), cardiomyopathy (hypertrophic, dilated), and hereditary channelopathies (eg, long QT syndrome, INFARCT LOCATION Brugada syndrome). Prevent with implantable cardioverter-defibrillator. LAYERS INVOLVED ECG CHANGES Progressive onset of HF over many years due to chronic ischemic myocardial damage. Myocardial hibernation\u2014potentially reversible LV systolic dysfunction in the setting of chronic ischemia. Contrast with myocardial stunning, a transient LV systolic dysfunction after a brief episode of acute ischemia. Most often due to rupture of coronary artery atherosclerotic plaque \u008e\u00a0acute thrombosis. \u008f\u00a0cardiac biomarkers (CK-MB, troponins) are diagnostic. NSTEMI STEMI Subendocardial Transmural Subendocardium (inner 1\/3) especially Full thickness of myocardial wall vulnerable to ischemia ST-segment depression, T-wave inversion ST-segment elevation, pathologic Q waves","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 309 Evolution of Commonly occluded coronary arteries: LAD > RCA > circumflex. myocardial infarction Symptoms: diaphoresis, nausea, vomiting, severe retrosternal pain, pain in left arm and\/or jaw, TIME shortness of breath, fatigue. 0\u201324 hours GROSS LIGHT MICROSCOPE COMPLICATIONS Wavy fibers (0\u20134 hr), early Ventricular arrhythmia, HF, coagulative necrosis (4\u201324 hr) cardiogenic shock A \u008e\u00a0cell content released into Occluded blood; edema, hemorrhage artery Reperfusion injury \u008e\u00a0free Dark mottling; radicals and \uf08f\u00a0Ca2+ influx pale with \u008e\u00a0hypercontraction of tetrazolium myofibrils (dark eosinophilic stain stripes) A 1\u20133 days Extensive coagulative necrosis Postinfarction fibrinous Tissue surrounding infarct pericarditis 3\u201314 days shows acute inflammation 2 weeks to several with neutrophils B months B Hyperemia Hyperemic border; Macrophages, then granulation Free wall rupture \u008e\u00a0tamponade; central yellow-brown tissue at margins C papillary muscle rupture softening C \u008e mitral regurgitation; interventricular septal rupture Contracted scar complete D due to macrophage-mediated D structural degradation \u008e\u00a0left- to-right shunt LV pseudoaneurysm (risk of rupture) Postcardiac injury syndrome, HF, arrhythmias, true ventricular aneurysm (risk of mural thrombus) Gray-white scar uploaded by medbooksvn","310 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Diagnosis of In the first 6 hours, ECG is the gold standard. Multiples of upper limit of normal 50 Troponin I myocardial infarction Cardiac troponin I rises after 4 hours (peaks 10 at 24 hr) and is \u008f for 7\u201310 days; more specific 5 than other protein markers. CK-MB increases after 6\u201312 hours (peaks CK-MB Normal at 16\u201324 hr) and is predominantly found 2 in myocardium but can also be released 1 from skeletal muscle. Useful in diagnosing reinfarction following acute MI because levels 12345678 return to normal after 48 hours. Days after MI onset ECG changes can include ST elevation (STEMI, transmural infarct), ST depression (NSTEMI, subendocardial infarct), hyperacute (peaked) T waves, T-wave inversion, and pathologic Q waves or poor R wave progression (evolving or old transmural infarct). ECG localization of INFARCT LOCATION LEADS WITH ST-SEGMENT ELEVATIONS OR Q WAVES STEMI Anteroseptal (LAD) V1\u2013V2 Anteroapical (distal LAD) V3\u2013V4 Anterolateral (LAD or LCX) V5\u2013V6 Lateral (LCX) I, aVL InFerior (RCA) Posterior (PDA) II, III, aVF V7\u2013V9, ST depression in V1\u2013V3 with tall R waves Scapula I aVR V1 V4 aVL V2 V5 Sternum II aVF V3 V6 III aVR II","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 311 Narrow complex Narrow QRS complex < 120 msec, rapid ventricular activation via normal ventricular conduction tachycardias system, tachycardia originates within or above AV node (supraventricular arrhythmia). ARRHYTHMIA DESCRIPTION ECG FINDINGS RR2 \u2260 RR3 \u2260 RR4 RR1 \u2260 Atrial fibrillation Irregularly irregular rate and rhythm with no discrete P waves. Arrhythmogenic activity usually originates from automatic Irregular baseline (absent P waves) Multifocal atrial foci near pulmonary vein ostia in left atrium. Common risk tachycardia factors include hypertension and CAD. May predispose to RR1 = RR2 = RR3 thromboembolic events, particularly stroke. Atrial flutter 4:1 sawtooth pattern Management: rate and rhythm control, cardioversion. Definitive Paroxysmal treatment is ablation of pulmonary vein ostia. Consider supraventricular anticoagulation based on stroke risk. tachycardia Irregularly irregular rate and rhythm with at least 3 distinct P wave morphologies, due to multiple ectopic foci in atria. Associated with underlying conditions such as COPD, pneumonia, HF. Rapid succession of identical, consecutive atrial depolarization waves causing \u201csawtooth\u201d appearance of P waves. Arrhythmogenic activity usually originates from reentry circuit around tricuspid annulus in right atrium. Treat like atrial fibrillation +\/\u2013 catheter ablation of region between tricuspid annulus and IVC. Most often due to a reentrant tract between atrium and ventricle, most commonly in AV node. Commonly presents with sudden- onset palpitations, lightheadedness, diaphoresis. Treatment: terminate reentry rhythm by slowing AV node conduction (eg, vagal maneuvers, IV adenosine), electrical cardioversion if hemodynamically unstable. Definitive treatment is catheter ablation of reentry tract. Wolff-Parkinson-White Most common type of ventricular preexcitation syndrome syndrome. Abnormal fast accessory conduction pathway from atria to ventricle (bundle of Kent) bypasses rate-slowing AV Delta wave node \u008e ventricles partially depolarize earlier \u008e characteristic delta wave with widened PR interval QRS complex and shortened PR interval. May Shortened PR interval result in reentry circuit \u008e supraventricular Normal PR interval tachycardia. Treatment: procainamide. Avoid AV nodal blocking drugs. uploaded by medbooksvn","312 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Wide complex Wide QRS complex \u2265 120 msec, slow ventricular activation outside normal ventricular conduction tachycardias system, tachycardia originates below AV node (ventricular arrhythmia). ARRHYTHMIA DESCRIPTION ECG FINDINGS Ventricular Typically regular rhythm, rate > 100. Most commonly due to tachycardia structural heart disease (eg, cardiomyopathy, scarring after myocardial infarction). High risk of sudden cardiac death. Torsades de Polymorphic ventricular tachycardia. Shifting sinusoidal pointes waveforms. May progress to ventricular fibrillation. Long QT interval predisposes to torsades de pointes. Caused by drugs, Ventricular \u0090\u00a0K+, \u0090 Mg2+, \u0090 Ca2+. fibrillation Torsades de pointes = twisting of the points Treatment: defibrillation for unstable patients, magnesium sulfate for stable patients. Drug-induced long QT (ABCDEF+NO): \u0083\t anti-Arrhythmics (Ia and III), Arsenic \u0083\t anti-Biotics (macrolides, fluoroquinolones) \u0083\t anti-Cychotics (haloperidol), Chloroquine \u0083\t anti-Depressants (TCAs), Diuretics (thiazides) \u0083\t anti-Emetics (ondansetron) \u0083\t anti-Fungals (Fluconazole) \u0083\t Navir (protease inhibitors) \u0083\t Opioids (methadone) Disorganized rhythm with no identifiable waves. Treatment: fatal without immediate CPR and defibrillation. No discernible rhythm Hereditary Inherited mutations of cardiac ion channels \u008e\u00a0abnormal myocardial action potential \u008e\u00a0\u008f\u00a0risk of channelopathies ventricular tachyarrhythmias and sudden cardiac death (SCD). Brugada syndrome Autosomal dominant; most commonly due to loss of function mutation of Na+ channels. Congenital long QT \u008f\u00a0prevalence in Asian males. ECG pattern of pseudo-right bundle branch block and ST-segment syndrome elevations in leads V1\u2013V2. Prevent SCD with ICD. Most commonly due to loss of function mutation of K+ channels (affects repolarization). Includes: \u0083\t Romano-Ward syndrome\u2014autosomal dominant, pure cardiac phenotype (no deafness). \u0083\t Jervell and Lange-Nielsen syndrome\u2014autosomal recessive, sensorineural deafness. Sick sinus Age-related degeneration of SA node. ECG can show bradycardia, sinus pause syndrome sinus pauses, sinus arrest, junctional escape beats.","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 313 Conduction blocks DESCRIPTION ECG FINDINGS ARRHYTHMIA Prolonged PR interval (>200 msec). Treatment: none required (benign and asymptomatic). First-degree AV block PR1 = PR2 = PR3 = PR4 Second-degree AV block Mobitz type I Progressive lengthening of PR interval until a beat is \u201cdropped\u201d (Wenckebach) (P wave not followed by QRS complex). Variable RR interval with a pattern (regularly irregular). Treatment: none required (usually asymptomatic) PR1 < PR1 < PR2 < PR3 P wave, absent QRS Mobitz type II Dropped beats that are not preceded by a change in PR interval. Third-degree May progress to 3rd-degree block, as it usually indicates a (complete) AV block structural abnormality such as ischemia or fibrosis. Bundle branch Treatment: usually a pacemaker. PR1 = PR1 = PR2 P wave, absent QRS block P waves and QRS complexes RR1 = RR2 P wave rhythmically dissociated. Atria and PP1 = PP2 = PP3 = PP4 P wave on QRS complex on T wave ventricles beat independently of each other. Atrial rate > ventricular rate. May be caused by Lym3 disease. Treatment: pacemaker. Interruption of conduction of normal left or right bundle branches. Affected ventricle depolarizes via slower myocyte- to-myocyte conduction from the unaffected ventricle, which depolarizes via the faster His-Purkinje system. Commonly due to degenerative changes (eg, cardiomyopathy, infiltrative disease). sinus pause Premature beats DESCRIPTION sinus pause ARRHYTHMIA Extra beats arising from ectopic foci in atria instead of the SA ECG FINDINGS node. Often 2\u00b0 to \u008f adrenergic drive (eg, caffeine consumption). Premature atrial Benign, but may increase risk for atrial fibrillation and flutter. contraction Narrow QRS complex with preceding P wave on ECG. Premature Ectopic beats arising from ventricle instead of the SA node. ventricular Shortened diastolic filling time \u008e \u0090 SV compared to a normal contraction beat. Prognosis is largely influenced by underlying heart disease. Wide QRS complex with no preceding P wave on ECG. uploaded by medbooksvn","314 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Myocardial infarction complications COMPLICATION TIMEFRAME FINDINGS NOTES Cardiac arrhythmia First few days to Can be supraventricular arrhythmias, Due to myocardial death and several months ventricular arrhythmias, or scarring. Important cause of conduction blocks. death before reaching the Peri-infarction 1\u20133 days hospital and within the first 48 pericarditis 2\u20137 days Pleuritic chest pain, pericardial hours post-MI. friction rub, ECG changes, and\/or Papillary muscle small pericardial effusion. Usually self-limited. rupture Can result in acute mitral Posteromedial >> anterolateral Interventricular 3\u20135 days regurgitation \u008e cardiogenic shock, papillary muscle rupture A , as septal rupture severe pulmonary edema. the posteromedial has single artery blood supply (PDA) Ventricular 3\u201314 days Symptoms can range from mild to whereas anterolateral has dual severe with cardiogenic shock and (LAD, LCX). pseudoaneurysm pulmonary edema. Macrophage-mediated Ventricular free 5\u201314 days May be asymptomatic. Symptoms degradation \u008e VSD \u008e \u008f O2 wall rupture may include chest pain, murmur, saturation and \u008f pressure in RV. arrhythmia, syncope, HF, embolus True ventricular 2 weeks to several from mural thrombus. Rupture \u008e Free wall rupture contained aneurysm months cardiac tamponade. by adherent pericardium or scar tissue\u2014does not contain Postcardiac injury Weeks to several Free wall rupture B \u008e cardiac endocardium or myocardium. syndrome months tamponade; acute form usually leads More likely to rupture than true to sudden death. aneurysm. Similar to pseudoaneurysm. LV hypertrophy and previous MI protect against free wall rupture. Fibrinous pericarditis due to autoimmune reaction. Outward bulge with contraction (\u201cdyskinesia\u201d). Associated with A fibrosis. Mitral valve Also called Dressler syndrome. Cardiac antigens released after injury \u008e deposition of immune complexes in pericardium \u008e inflammation. B Pap LV Ventricular Pseudoaneaurysm aneurysm","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 315 Acute coronary Unstable angina\/NSTEMI\u2014Anticoagulation (eg, heparin), antiplatelet therapy (eg, aspirin) syndrome treatments + ADP receptor inhibitors (eg, clopidogrel), \u03b2-blockers, ACE inhibitors, statins. Symptom control with nitroglycerin +\/\u2013 morphine. STEMI\u2014In addition to above, reperfusion therapy most important (percutaneous coronary intervention preferred over fibrinolysis). If RV affected (eg, RCA occlusion), support venous return\/ preload to maintain cardiac output (eg, IV fluids, avoiding nitroglycerin). Cardiomyopathies Most common cardiomyopathy (90% of cases). Leads to systolic dysfunction. Dilated Often idiopathic or familial (eg, due to mutation of Displays eccentric hypertrophy A cardiomyopathy TTN gene encoding the sarcomeric protein titin). A (sarcomeres added in series). Compare Other etiologies include drugs (eg, alcohol, to athlete\u2019s heart, where LV and RV RV LV cocaine, doxorubicin), infection (eg, coxsackie enlargement facilitates \u008f SV and \u008f CO. B virus, Chagas disease), ischemia (eg, CAD), Stress cardiomyopathy (also called takotsubo Hypertrophic systemic conditions (eg, hemochromatosis, cardiomyopathy, broken heart syndrome)\u2014 cardiomyopathy sarcoidosis, thyrotoxicosis, wet beriberi), ventricular apical ballooning likely due B peripartum cardiomyopathy. to \u008f sympathetic stimulation (eg, stressful situations). RV LV Findings: HF, S3, systolic regurgitant murmur, dilated heart on echocardiogram, balloon Diastolic dysfunction ensues. Restrictive\/infiltrative appearance of heart on CXR. Displays ventricular concentric hypertrophy cardiomyopathy Treatment: Na+ restriction, ACE inhibitors\/ARBs, (sarcomeres added in parallel) B , often \u03b2-blockers, sacubitril, diuretics, mineralocorticoid septal predominance. Myofibrillar disarray receptor blockers (eg, spironolactone), ICD, heart and fibrosis. transplant. Classified as hypertrophic obstructive cardiomyopathy when LV outflow tract is 60\u201370% of cases are familial, autosomal dominant obstructed. Asymmetric septal hypertrophy (most commonly due to mutations in genes and systolic anterior motion of mitral valve encoding sarcomeric proteins, such as myosin \u008e\u00a0outflow obstruction \u008e\u00a0dyspnea, possible binding protein C and \u03b2-myosin heavy chain). syncope. Causes syncope during exercise and may lead Other causes of concentric LV hypertrophy: to sudden death (eg, in young athletes) due to chronic HTN, Friedreich ataxia. ventricular arrhythmia. Diastolic dysfunction ensues. Can have low- Findings: S4, systolic murmur. May see mitral voltage ECG despite thick myocardium regurgitation due to impaired mitral valve closure. (especially in amyloidosis). Treatment: cessation of high-intensity athletics, L\u00f6ffler endocarditis\u2014associated with use of \u03b2-blocker or nondihydropyridine Ca2+ hypereosinophilic syndrome; histology shows channel blockers (eg, verapamil). ICD if high risk. eosinophilic infiltrates in myocardium. Avoid drugs that decrease preload (eg, diuretics, vasodilators). Postradiation fibrosis, L\u00f6ffler endocarditis, Endocardial fibroelastosis (thick fibroelastic tissue in endocardium of young children), Amyloidosis, Sarcoidosis, Hemochromatosis (PLEASe Help!). uploaded by medbooksvn","316 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Heart failure Clinical syndrome of cardiac pump dysfunction \u008e\u00a0congestion and low perfusion. Symptoms A include dyspnea, orthopnea, fatigue; signs include S3 heart sound, rales, jugular venous distention (JVD), pitting edema A . Left heart failure Orthopnea Systolic dysfunction\u2014heart failure with reduced ejection fraction (HFrEF), \u008f\u00a0EDV; \u0090\u00a0contractility Paroxysmal nocturnal often 2\u00b0 to ischemia\/MI or dilated cardiomyopathy. dyspnea Pulmonary edema Diastolic dysfunction\u2014heart failure with preserved ejection fraction (HFpEF), normal EDV; Right heart failure \u0090\u00a0compliance (\u008f\u00a0EDP) often 2\u00b0 to myocardial hypertrophy. Congestive hepatomegaly Right HF most often results from left HF. Cor pulmonale refers to isolated right HF due to Jugular venous pulmonary cause. distention Peripheral edema ACE inhibitors, ARBs, angiotensin receptor\u2013neprilysin inhibitors, \u03b2-blockers (except in acute decompensated HF), and aldosterone receptor antagonists \u0090 mortality in HFrEF. Loop and HFrEF thiazide diuretics are used mainly for symptomatic relief. Hydralazine with nitrate therapy \u2193Contractility improves both symptoms and mortality in select patients. Shortness of breath when supine: \u008f venous return from redistribution of blood (immediate gravity effect) exacerbates pulmonary vascular congestion. Breathless awakening from sleep: \u008f venous return from redistribution of blood, reabsorption of peripheral edema, etc. \u008f pulmonary venous pressure \u008e pulmonary venous distention and transudation of fluid. Presence of hemosiderin-laden macrophages (\u201cHF\u201d cells) in lungs. \u008f central venous pressure \u008e \u008f resistance to portal flow. Rarely, leads to \u201ccardiac cirrhosis.\u201d Associated with nutmeg liver (mottled appearance) on gross exam. \u008f venous pressure. Pressure (mm Hg) \u008f venous pressure \u008e fluid transudation. \uf08f CO Deleterious cardiac remodeling Neurohormonal \uf08f sympathetic tone \uf08f renin-angiotensin-aldosterone system stress Volume (mL) Catecholamines (\u02dc 1) Catecholamines (\u00b0 1) Angiotensin II (AT1) Angiotensin II, aldosterone, ADH (V1) ADH (V2) HFpEF \u2193Compliance \uf08f contractility \uf08f heart rate Vasoconstriction \uf08f circulating volume Pressure (mm Hg) Volume (mL) \uf08f arterial tone \uf08f venous tone Hemodynamic Maintained BP \uf08f venous return to heart stress Maintained CO (preload) \uf08f stroke volume","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 317 High-output heart Uncommon form of HF characterized by \u008f CO. High-output state is due to \u0090 SVR from either failure vasodilation or arteriovenous shunting. Causes include severe obesity, advanced cirrhosis, severe anemia, hyperthyroidism, wet beriberi, Paget disease of bone. Presents with symptoms and signs of pulmonary and\/or systemic venous congestion. Shock Inadequate organ perfusion and delivery of nutrients necessary for normal tissue and cellular function. Initially may be reversible but life threatening if not treated promptly. TYPE CAUSED BY MECHANISM SKIN CVP PCWP CO SVR SVO2 Hypovolemic shock Hemorrhage, Volume depletion Cold, \u0090 \u0090\u0090 \u008f\u0090 dehydration, clammy burns Left heart \u008f \u008f\u0090 \u008f\u0090 dysfunction Warm, Cardiogenic shock MI, HF, valvular dry \u008f \u0090\u0090 \u008f\u008f dysfunction, Impeded \u008f \u008f\u0090 \u008f\u0090 arrhythmia cardio\u00adpulmonary \u0090 \u0090\u008f \u0090\u008f blood flow \u0090 \u0090\u0090 \u0090 normal\/\u008f Obstructive shock PE, tension pneumothorax Systemic vasodilation Cardiac tamponade Distributive shock Sepsis (early), anaphylaxis CNS injury \u0090 = 1\u00b0 disturbance driving the shock. Cardiac tamponade Compression of the heart by fluid (eg, blood, effusions) \u008e \u0090 CO. Equilibration of diastolic A pressures in all 4 chambers. B Findings: Beck triad (hypotension, distended neck veins, distant heart sounds), \u008f HR, pulsus RV paradoxus. ECG shows low-voltage QRS and electrical alternans A (due to \u201cswinging\u201d movement LV of heart in large effusion). Echocardiogram shows pericardial effusion (arrows in B ), systolic RA collapse, diastolic RV collapse, and IVC plethora. Treatment: pericardiocentesis or surgical drainage. Pulsus paradoxus\u2014\u0090 in amplitude of systolic BP by > 10 mm\u00a0Hg during inspiration. \u008f venous return during inspiration \u008e \u008f RV filling \u008e interventricular septum bows toward LV (due to \u0090 pericardial compliance) \u008e \u0090 LV ejection volume \u008e \u0090 systolic BP. Seen in constrictive pericarditis, obstructive pulmonary disease (eg, Croup, OSA, Asthma, COPD), cardiac Tamponade (pea COAT). uploaded by medbooksvn","318 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Syncope Transient loss of consciousness caused by a period of \u0090\u00a0cerebral blood flow. Types: \u0083\t Reflex (most common)\u2014vasovagal (common faint), situational (eg, coughing\/sneezing, swallowing, defecation, micturition), carotid sinus hypersensitivity. \u0083\t Orthostatic\u2014hypovolemia, drugs (eg, antihypertensives), autonomic dysfunction. \u0083\t Cardiac\u2014arrhythmias, structural (eg, aortic stenosis, HCM). Infective endocarditis Infection of the endocardial surface of the Mitral valve (most common) > aortic valve. heart, typically involving \u22651 heart valves. Tricuspid valve involvement is associated with injection drug use (don\u2019t \u201ctri\u201d drugs). Caused by bacteria >> fungi. Forms: \u0083\t Acute\u2014classically S aureus (high virulence). Common associations: Large destructive vegetations A on \u0083\t Prosthetic valves\u2014S epidermidis previously normal valves. Rapid onset. \u0083\t GI\/GU procedures\u2014Enterococcus \u0083\t Subacute\u2014classically viridans streptococci \u0083\t Colon cancer\u2014S gallolyticus (low virulence). Smaller vegetations on \u0083\t Gram \u229d\u2014HACEK organisms congenitally abnormal or diseased valves. (Haemophilus, Aggregatibacter [formerly Sequela of dental procedures. Gradual Actinobacillus], Cardiobacterium, Eikenella, onset. Kingella) \u0083\t Culture \u229d\u2014Coxiella, Bartonella Presents with fever (most common), new \u0083\t Injection drug use\u2014S aureus, Pseudomonas, murmur, vascular and immunologic Candida phenomena. Endothelial injury \u008e formation of vegetations Vascular phenomena\u2014septic embolism, consisting of platelets, fibrin, and microbes petechiae, splinter hemorrhages (linear on heart valves \u008e valve regurgitation, septic hemorrhagic lesions on nail bed B ), Janeway embolism (systemic circulation in left-sided lesions (painless, flat, erythematous lesions on endocarditis, pulmonary in right-sided). palms or soles). Diagnosis requires multiple blood cultures and Immunologic phenomena\u2014immune complex echocardiography. deposition, glomerulonephritis, Osler nodes (painful [\u201cOuchy\u201d], raised, violaceous lesions on finger or toe pads C ), Roth spots (Retinal hemorrhagic lesions with pale centers D ). ABCD Nonbacterial Also called marantic endocarditis. Rare, Associated with the hypercoagulable state seen thrombotic noninfective. Vegetations typically arise on in advanced malignancy (especially pancreatic endocarditis mitral or aortic valve and consist of sterile, adenocarcinoma) or SLE (called Libman- platelet-rich thrombi that dislodge easily. Sacks endocarditis in this setting). Usually asymptomatic until embolism occurs.","Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology SEC TION III 319 Rheumatic fever A consequence of pharyngeal infection with J\u2665NES (major criteria): group A \u03b2-hemolytic streptococci. Late Joint (migratory polyarthritis) Syphilitic heart sequelae include rheumatic heart disease, \u2665 (carditis) disease which affects heart valves\u2014mitral > aortic >> Nodules in skin (subcutaneous) Acute pericarditis tricuspid (high-pressure valves affected most). Erythema marginatum (evanescent rash with A Early valvular regurgitation, late valvular ring margin) stenosis. Sydenham chorea (involuntary irregular movements of limbs and face) Associated with Aschoff bodies (granuloma with giant cells, Anitschkow cells (enlarged macrophages with ovoid, wavy, rodlike nucleus), \u008f anti-streptolysin O (ASO) and \u008f\u00a0anti-DNase B titers. Immune mediated (type II hypersensitivity); not a direct effect of bacteria. Antibodies to M protein cross-react with self antigens, often myosin (molecular mimicry). Treatment\/prophylaxis: penicillin. 3\u00b0 syphilis disrupts the vasa vasorum of the Can result in aneurysm of ascending aorta or aorta with consequent atrophy of vessel wall aortic arch, aortic insufficiency. and dilation of aorta and valve ring. May see calcification of aortic root, ascending aortic arch, and thoracic aorta. Leads to \u201ctree bark\u201d appearance of aorta. Inflammation of the pericardium (red arrows in A ). Commonly presents with sharp pain, aggravated by inspiration, and relieved by sitting up and leaning forward. Often complicated by pericardial effusion (between yellow arrows in A ). Presents with friction rub. ECG changes include widespread\/diffuse ST-segment elevation and\/or PR depression. Usually idiopathic, but may be due to viral infections (eg, coxsackievirus B), malignancy (metastasis), cardiac surgery, thoracic radiotherapy (early), MI (eg, postcardiac injury syndrome), autoimmune diseases (eg, SLE, rheumatoid arthritis), renal failure (uremia). Treatment: NSAIDs, colchicine, glucocorticoids, dialysis (uremia). Constrictive Chronic inflammation of pericardium \u008e pericardial fibrosis +\/\u2013 calcification \u008e limited space pericarditis for expansion \u008e\u00a0\u0090\u00a0ventricular filling. Usually idiopathic, but may be due to viral infections, cardiac surgery, thoracic radiotherapy (late). TB is the most common cause in resource-limited countries. \u0090\u00a0EDV \u008e\u00a0\u0090\u00a0CO \u008e\u00a0\u0090\u00a0venous return. Presents with dyspnea, peripheral edema, jugular venous\u00a0distention, Kussmaul sign, pulsus paradoxus, pericardial knock. uploaded by medbooksvn","320 SEC TION III Cardiovascular\u2003 \uf07d\u2009CARDIOVASCULAR\u2014Pathology Kussmaul sign Paradoxical \u008f in JVP on inspiration (normally, inspiration \u008e negative intrathoracic pressure Myocarditis \u008e \u008f venous return \u008e \u0090 JVP). Hereditary Impaired RV filling \u008e RV cannot accommodate \u008f venous return during inspiration \u008e blood hemorrhagic backs up into vena cava \u008e Kussmaul sign. May be seen with constrictive pericarditis, restrictive telangiectasia cardiomyopathy, right HF, massive pulmonary embolism, right atrial or ventricular tumors. Cardiac tumors Inflammation of myocardium. Major cause of SCD in adults < 40 years old. Presentation highly variable, can include dyspnea, chest pain, fever, arrhythmias (persistent Myxomas tachycardia out of proportion to fever is characteristic). A Multiple causes: RV \u0083\t Viral (eg, adenovirus, coxsackie B, parvovirus B19, HIV, HHV-6, COVID-19); lymphocytic RA LV infiltrate with focal necrosis highly indicative of viral myocarditis LA \u0083\t Parasitic (eg, Trypanosoma cruzi, Toxoplasma gondii) Ao \u0083\t Bacterial (eg, Borrelia burgdorferi, Mycoplasma pneumoniae, Corynebacterium diphtheriae) \u0083\t Toxins (eg, carbon monoxide, black widow venom) Rhabdomyomas \u0083\t Rheumatic fever \u0083\t Drugs (eg, doxorubicin, cocaine) \u0083\t Autoimmune (eg, Kawasaki disease, sarcoidosis, SLE, polymyositis\/dermatomyositis) Complications include sudden death, arrhythmias, heart block, dilated cardiomyopathy, HF, mural thrombus with systemic emboli. Also called Osler-Weber-Rendu syndrome. Autosomal dominant disorder of blood vessels. Findings: blanching lesions (telangiectasias) on skin and mucous membranes, recurrent epistaxis, AVMs (eg, brain, lung, liver), GI bleeding, hematuria. Arteriovenous malformation\u2014abnormal, high-flow connection between artery and vein. Most common cardiac tumor is a metastasis (eg, melanoma). Most common 1\u00b0 cardiac tumor in adults (arrows in A ). 90% occur in the atria (mostly left atrium). Myxomas are usually described as a \u201cball valve\u201d obstruction in the left atrium (associated with multiple syncopal episodes). IL-6 production by tumor \u008e constitutional symptoms (eg, fever, weight loss). May auscultate early diastolic \u201ctumor plop\u201d sound (mimics mitral stenosis). Histology: gelatinous material, myxoma cells immersed in glycosaminoglycans. Adults make 6 myxed drinks. Most frequent 1\u00b0 cardiac tumor in children (associated with tuberous sclerosis). Histology: hamartomatous growths. More common in the ventricles.","Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology SEC TION III 321 ` \u2009C A R D I O VA S C UL A R \u2014 P H A R M A C O LO G Y Hypertension treatment Primary (essential) Thiazide diuretics, ACE inhibitors, angiotensin hypertension II receptor blockers (ARBs), dihydropyridine Ca2+ channel blockers. Hypertension with Diuretics, ACE inhibitors\/ARBs, \u03b2-blockers \u03b2-blockers must be used cautiously in heart failure (compensated HF), aldosterone antagonists. decompensated HF and are contraindicated in cardiogenic shock. Hypertension with ACE inhibitors\/ARBs, Ca2+ channel blockers, diabetes mellitus thiazide diuretics, \u03b2-blockers. In HF, ARBs may be combined with the neprilysin inhibitor sacubitril. Hypertension in ARBs, Ca2+ channel blockers, thiazide diuretics, asthma cardioselective \u03b2-blockers. ACE inhibitors\/ARBs are protective against diabetic nephropathy. Hypertension in Nifedipine, methyldopa, labetalol, hydralazine. pregnancy \u03b2-blockers can mask hypoglycemia symptoms. Avoid nonselective \u03b2-blockers to prevent \u03b22\u2011receptor\u2013induced bronchoconstriction. Avoid ACE inhibitors to prevent confusion between drug or asthma-related cough. New moms love hugs. uploaded by medbooksvn","322 SEC TION III Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology Cardiovascular agents and molecular targets DIHYDROPYRIDINE Gi AGONISTS Gs AGONISTS CALCIUM CHANNEL Epi\/NE (\u03b12) EPproi s(\u03b2ta2g) landins BLOCKERS Prostacyclin L-type voltage Fenoldopam (D1) Amlodipine gated Ca2+ Adenosine Clevidipine channel Nicardipine Nifedipine Nimodipine Gi G PDE-3 INHIBITOR s Milrinone Action Adenylate Ca2+ potent\u2013ia\u2013l cyclase SERCA \u2013 Ca2+ Ca2+ \uf069 cytosolic Ca2+ brarnizeation Ca2+\u2013calmodulin cAMP ATP complex AMP PDE-5 INHIBITOR depolMaem Sildena\ufb01l Ca2+ PDE-3 MLC-kinase PKA Ca2+ Sarcoplasmic PLB reticulum Ca2+ Myosin-P Myosin CONTRACTION + actin + actin RELAXATION PDE-5 IP3 MLC phosphatase GMP GTP Gq cGMP Rho kinase Guanylate cyclase L-arginine Gq AGONISTS NO synthase NO Natriuretic NATRIURETIC PEPTIDE peptide AGONISTS EEnpdi\/oNtEhe(\u03b1lin1)-1 receptor Angiotensin-II ANP Vasopressin Smooth muscle cell Bacterial NITRATES BNP LPS NO di usion Endothelial cell NO synthase NO L-arginine Ca2+ Ca2+ Acetylcholine Receptor(s) \u03b1Br2a-dagykoinniisnts Vascular lumen Cytokines Histamine Serotonin Shear stress","Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology SEC TION III 323 Calcium channel Amlodipine, clevidipine, nicardipine, nifedipine, nimodipine (dihydropyridines, act on vascular blockers smooth muscle); diltiazem, verapamil (nondihydropyridines, act on heart). MECHANISM Block voltage-dependent L-type calcium channels of cardiac and smooth muscle \u008e\u00a0\u0090\u00a0muscle contractility. CLINICAL USE Vascular smooth muscle\u2014amlodipine = nifedipine > diltiazem > verapamil. ADVERSE EFFECTS Heart\u2014verapamil > diltiazem > amlodipine = nifedipine. Dihydropyridines (except nimodipine): hypertension, angina (including vasospastic type), Raynaud Hydralazine phenomenon. Dihydropyridine mainly dilates arteries. MECHANISM Nimodipine: subarachnoid hemorrhage (prevents cerebral vasospasm). CLINICAL USE Nicardipine, clevidipine: hypertensive urgency or emergency. ADVERSE EFFECTS Nondihydropyridines: hypertension, angina, atrial fibrillation\/flutter. Gingival hyperplasia. Hypertensive Dihydropyridine: peripheral edema, flushing, dizziness. emergency Nondihydropyridine: cardiac depression, AV block, hyperprolactinemia (verapamil), constipation. Nitroprusside Fenoldopam \u008f cGMP \u008e smooth muscle relaxation. Hydralazine vasodilates arterioles > veins; afterload reduction. Nitrates Severe hypertension (particularly acute), HF (with organic nitrate). Safe to use during pregnancy. MECHANISM Frequently coadministered with a \u03b2-blocker to prevent reflex tachycardia. CLINICAL USE ADVERSE EFFECTS Compensatory tachycardia (contraindicated in angina\/CAD), fluid retention, headache, angina, drug-induced lupus. Treat with labetalol, clevidipine, fenoldopam, nicardipine, nitroprusside. Short acting vasodilator (arteries = veins); \u008f cGMP via direct release of NO. Can cause cyanide toxicity (releases cyanide). Dopamine D1 receptor agonist\u2014coronary, peripheral, renal, and splanchnic vasodilation. \u0090\u00a0BP, \u008f\u00a0natriuresis. Also used postoperatively as an antihypertensive. Can cause hypotension, tachycardia, flushing, headache, nausea. Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate. Vasodilate by \u008f NO in vascular smooth muscle \u008e \u008f in cGMP and smooth muscle relaxation. Dilate veins >> arteries. \u0090 preload. Angina, acute coronary syndrome, pulmonary edema. Reflex tachycardia (treat with \u03b2-blockers), methemoglobinemia, hypotension, flushing, headache, \u201cMonday disease\u201d in industrial nitrate exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend \u008e\u00a0tachycardia, dizziness, headache upon reexposure. Contraindicated in right ventricular infarction, hypertrophic cardiomyopathy, and with concurrent PDE-5 inhibitor use. uploaded by medbooksvn","324 SEC TION III Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology Antianginal therapy Goal is reduction of myocardial O2 consumption (MVO2) by \u0090 1 or more of the determinants of MVO2: end-diastolic volume, BP, HR, contractility. COMPONENT NITRATES \u03b2-BLOCKERS NITRATES + \u03b2-BLOCKERS End-diastolic volume \u0090 No effect or \u008f No effect or \u0090 Blood pressure \u0090 \u0090 \u0090 Contractility \u008f (reflex response) \u0090 Little\/no effect Heart rate \u008f (reflex response) \u0090 No effect or \u0090 Ejection time \u0090 \u008f Little\/no effect MVO2 \u0090 \u0090 \u0090\u0090 Verapamil is similar to \u03b2-blockers in effect. Ranolazine Inhibits the late phase of inward sodium current thereby reducing diastolic wall tension and oxygen consumption. Does not affect heart rate or blood pressure. MECHANISM Refractory angina. CLINICAL USE ADVERSE EFFECTS Constipation, dizziness, headache, nausea. Sacubitril A neprilysin inhibitor; prevents degradation of bradykinin, natriuretic peptides, angiotensin II, and substance P \u008e\u00a0\u008f\u00a0vasodilation, \u0090 ECF volume. MECHANISM Used in combination with valsartan (an ARB) to treat HFrEF. CLINICAL USE ADVERSE EFFECTS Hypotension, hyperkalemia, cough, dizziness; contraindicated with ACE inhibitors due to angioedema (both drugs \u008f\u00a0bradykinin). Lipid-lowering agents LDL HDL TRIGLYCERIDES MECHANISM ADVERSE EFFECTS DRUG \u0090\u0090\u0090 \u008f\u0090 Inhibit HMG-CoA reductase Hepatotoxicity (\u008f LFTs), \u008e\u00a0\u0090\u00a0cholesterol synthesis; myopathy (especially Statins \u008f slightly \u008f slightly \u008e\u00a0\u0090\u00a0intrahepatic cholesterol when used with fibrates Atorvastatin, \u008e\u00a0\u008f\u00a0LDL receptor recycling or niacin) lovastatin, \u008f\/\u2014 \u0090\/\u2014 \u008e\u00a0\u008f\u00a0LDL catabolism pravastatin, GI upset, \u0090\u00a0absorption of rosuvastatin, \u0090\u00a0in mortality in patients with other drugs and fat- simvastatin CAD soluble vitamins Bile acid resins \u0090\u0090 Disrupt enterohepatic bile acid Rare \u008f LFTs, diarrhea Cholestyramine, circulation \u008e\u00a0compensatory colesevelam, \u008f\u00a0conversion of cholesterol colestipol to bile \u008e\u00a0\u0090\u00a0intrahepatic cholesterol \u008e\u00a0\u008f\u00a0LDL receptor Ezetimibe \u0090\u0090 recycling Prevents cholesterol absorption at small intestine brush border","Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology SEC TION III 325 Lipid-lowering agents (continued) DRUG LDL HDL TRIGLYCERIDES MECHANISM ADVERSE EFFECTS Fibrates \u0090 \u008f \u0090\u0090\u0090 Activate PPAR-\u03b1 Myopathy (\u008f risk with Fenofibrate, \u008e\u00a0upregulate LPL \u008e\u00a0\u008f\u00a0TG statins), cholesterol gemfi rozil \u0090 clearance gallstones (via inhibition of cholesterol Niacin \u0090\u0090 \u008f\u008f Activate PPAR-\u03b1 \u008e\u00a0induce 7\u03b1-hydroxylase) HDL synthesis PCSK9 inhibitors \u0090\u0090\u0090 \u008f \u0090 Flushed face Alirocumab, \u008f slightly \u008f slightly \u0090\u00a0at high Inhibits lipolysis (hormone- (prostaglandin mediated; evolocumab sensitive lipase) in adipose \u0090\u00a0by NSAIDs or long- doses tissue; reduces hepatic term use) Fish oil and marine VLDL synthesis omega-3 fatty acids Hyperglycemia Inactivation of LDL-receptor Hyperuricemia degradation \u008e\u00a0\u008f\u00a0removal of Myalgias, delirium, LDL from bloodstream dementia, other Believed to decrease FFA neurocognitive effects delivery to liver and decrease activity of TG-synthesizing Nausea, fishlike taste enzymes Liver Blood Enterocyte Intestinal lumen Acetyl-CoA Triacylglyceride ApoE CHY Lymphatics CHY CHOLESTEROL receptor ABSORPTION HMG-CoA CHY LPL PPAR-\u03b1 Cholesterol Ezetimibe HMG-CoA rem FFA reductase Bile acids Cholesterol HDL FFA FFA Mevalonate pool Bile acids Cholesterol VLDL VLDL BILE ACID CHOLESTEROL REABSORPTION Niacin LPL SYNTHESIS HDL LPL- Bile acid resins receptor Cholestyramine Statins FFA UPREGULATION Colesevelam Atorvastatin HDL Colestipol Lovastatin HDL Lipolysis Pravastatin FFA Adipose tissue Fibrates Rosuvastatin Feno\ufb01brate Simvastatin LDL Gem\ufb01brozil LDL LDL receptor ADIPOSE LIPOLYSIS PCSK9 LDL-RECEPTOR Niacin DEGRADATION PCSK9 inhibitors Alirocumab Evolocumab uploaded by medbooksvn","326 SEC TION III Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology Digoxin Direct inhibition of Na+\/K+-ATPase. Na+\/Ca2+ Digoxin \u008e\u00a0indirect inhibition of Na+\/Ca2+ exchanger. exchanger Na+\/K+- MECHANISM \u008f [Ca2+]i \u008e\u00a0positive inotropy. Stimulates vagus ATPase CLINICAL USE nerve \u008e \u0090 HR. Ca2+ Na+ K+ ADVERSE EFFECTS SR \u2191\u2191Ca2+ \u2191TnC Ca2+ \u2191 cardiac ANTIDOTE binding contraction HF (\u008f contractility); atrial fibrillation (\u0090 conduction at AV node and depression of SA node). Cholinergic effects (nausea, vomiting, diarrhea), blurry yellow vision (\u201cvan Glow\u201d), arrhythmias, AV block. Can lead to hyperkalemia, which indicates poor prognosis. Factors predisposing to toxicity: renal failure (\u0090 excretion), hypokalemia (permissive for digoxin binding at K+-binding site on Na+\/K+-ATPase), drugs that displace digoxin from tissue-binding sites, and \u0090\u00a0clearance (eg, verapamil, amiodarone, quinidine). Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+. Antiarrhythmics\u2014 Slow or block conduction (especially in depolarized cells). \u0090 slope of phase 0 depolarization. sodium channel \u008f action at faster HR. State dependent \u008f HR \uf08e shorter diastole, Na+ channels spend less time in blockers (class I) Class IA resting state (drugs dissociate during this state) \uf08e less time for drug to dissociate from receptor. MECHANISM Effect most pronounced in IC>IA>IB due to relative binding strength. Fast taxi CAB. CLINICAL USE Quinidine, procainamide, disopyramide. 0 mV ADVERSE EFFECTS \u201cThe queen proclaims Diso\u2019s pyramid.\u201d 0 mSpVlhoapseeo0f Class IB Moderate Na+ channel blockade. SloIpNea of \u008f AP duration, \u008f effective refractory period phase 0 MECHANISM (ERP) in ventricular action potential, \u008f QT INa CLINICAL USE interval, some K+ channel blocking effects. ADVERSE EFFECTS Both atrial and ventricular arrhythmias, especially reentrant and ectopic SVT and VT. Cinchonism (headache, tinnitus with 0 mV quinidine), reversible SLE-like syndrome Slope of (procainamide), HF (disopyramide), thrombocytopenia, torsades de pointes due to 0 mSpVlhoIapNseaeo0f \u008f\u00a0QT interval. phase 0 INa Lidocaine, phenytoin, mexiletine. \u201cI\u2019d Buy Liddy\u2019s phine Mexican tacos.\u201d Weak Na+ channel blockade. \u0090 AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. Acute ventricular arrhythmias (especially post- MI), digitalis-induced arrhythmias. IB is Best post-MI. CNS stimulation\/depression, cardiovascular depression. 0 mV 0 mSVlope of phase 0 SloIpNea of phase 0","Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology SEC TION III 327 Antiarrhythmics\u2014sodium channel blockers (class I) (continued) Class IC Flecainide, propafenone. 0 mV \u201cCan I have fries, please?\u201d Slope of MECHANISM Strong Na+ channel blockade. phase 0 Significantly prolongs ERP in AV node and INa accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue. Minimal effect on AP duration. CLINICAL USE SVTs, including atrial fibrillation. Only as a last resort in refractory VT. ADVERSE EFFECTS Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease. Antiarrhythmics\u2014 Metoprolol, propranolol, esmolol, atenolol, timolol, carvedilol. \u03b2-blockers (class II) Decrease SA and AV nodal activity by \u0090 cAMP, \u0090 Ca2+ currents. Suppress abnormal pacemakers by MECHANISM \u0090\u00a0slope of phase 4. CLINICAL USE AV node particularly sensitive\u2014\u008f PR interval. Esmolol very short acting. ADVERSE EFFECTS SVT, ventricular rate control for atrial fibrillation and atrial flutter, prevent ventricular arrhythmia post-MI. Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV block, HF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia. Metoprolol can cause dyslipidemia. Propranolol can exacerbate vasospasm in vasospastic angina. \u03b2-blockers (except the nonselective \u03b1- and \u03b2-antagonists carvedilol and labetalol) cause unopposed \u03b11-agonism if given alone for pheochromocytoma or for cocaine toxicity (unsubstantiated). Treat \u03b2-blocker overdose with saline, atropine, glucagon. Membrane potential (mv) 60 Decrease slope Prolonged of phase 4 repolarization 30 depolarization (at AV node) 0 \u201330 Threshold potential \u201360 \u201390 100 200 300 400 500 600 700 800 0 Time (ms) Pacemaker cell action potential uploaded by medbooksvn","328 SEC TION III Cardiovascular\u2003 \uf07d\u2009Cardiovascular\u2014pharmacology Antiarrhythmics\u2014 Amiodarone, Ibutilide, Dofetilide, Sotalol. AIDS. potassium channel blockers (class III) \u008f AP duration, \u008f ERP, \u008f QT interval. Remember to check PFTs, LFTs, and TFTs when using amiodarone. MECHANISM Atrial fibrillation, atrial flutter; ventricular CLINICAL USE tachycardia (amiodarone, sotalol). Amiodarone is lipophilic and has class I, II, III, ADVERSE EFFECTS and IV effects. Sotalol\u2014torsades de pointes, excessive \u03b2 Antiarrhythmics\u2014 blockade. 0 mV calcium channel blockers (class IV) Ibutilide\u2014torsades de pointes. Markedly prolonged Amiodarone\u2014pulmonary fibrosis, repolarization (IK) MECHANISM CLINICAL USE hepatotoxicity, hypothyroidism or \u221285 mV ADVERSE EFFECTS hyperthyroidism (amiodarone is 40% iodine by weight), acts as hapten (corneal Cell action potential deposits, blue\/gray skin deposits resulting in photodermatitis), neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, HF). Diltiazem, verapamil. Decrease conduction velocity, \u008f ERP, \u008f PR Membrane potential (mv) 60 Slow rise of Prolonged interval. 30 action potential repolarization 0 (at AV node) Prevention of nodal arrhythmias (eg, SVT), \u201330 rate control in atrial fibrillation. \u201360 Threshold \u201390 potential Constipation, flushing, edema, cardiovascular effects (HF, AV block, sinus node depression). 0 100 200 300 400 500 600 700 800 Time (ms) Other antiarrhythmics \u008f K+ out of cells \u008e hyperpolarizing the cell and \u0090 ICa, decreasing AV node conduction. Drug of Adenosine choice in diagnosing\/terminating certain forms of SVT. Very short acting (~ 15 sec). Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists). Adverse effects Magnesium include flushing, hypotension, chest pain, sense of impending doom, bronchospasm. Effective in torsades de pointes and digoxin toxicity. Ivabradine IVabradine prolongs slow depolarization (phase \u201cIV\u201d) by selectively inhibiting \u201cfunny\u201d sodium channels (If). MECHANISM Chronic HFrEF. CLINICAL USE ADVERSE EFFECTS Luminous phenomena\/visual brightness, hypertension, bradycardia.","HIGH-YIELD SYSTEMS Endocrine \u201cIf you skew the endocrine system, you lose the pathways to self.\u201d `\tEmbryology\t 330 \u2014Hilary Mantel `\tAnatomy\t 331 `\tPhysiology\t 332 \u201cSometimes you need a little crisis to get your adrenaline flowing and help `\tPathology\t 342 you realize your potential.\u201d `\tPharmacology\t 358 \u2014Jeannette Walls, The Glass Castle \u201cChocolate causes certain endocrine glands to secrete hormones that affect your feelings and behavior by making you happy.\u201d \u2014Elaine Sherman, Book of Divine Indulgences The endocrine system comprises widely distributed organs that work in a highly integrated manner to orchestrate a state of hormonal equilibrium within the body. Generally speaking, endocrine diseases can be classified either as diseases of underproduction or overproduction, or as conditions involving the development of mass lesions\u2014which themselves may be associated with underproduction or overproduction of hormones. Therefore, study the endocrine system first by learning the glands, their hormones, and their regulation, and then by integrating disease manifestations with diagnosis and management. Take time to learn the multisystem connections. 329 uploaded by medbooksvn"]