Cardiovascular Pathology Case-based_Gross and Microscopic

Cardiovascular Pathology Gross and Microscopic An Integrated & Case-based Learning Sequence Companion: Cardiovascular Pathology Interactive Questions and Answers

Marc Imhotep Cray, M.D.

Prepared and presented by: Marc Imhotep Cray, M.D.

Photo: Photograph of chordae tendineae attached to papillary muscles of a ventricle. From Seeley’s Anatomy & Physiology. 10th ed. New York, NY: McGraw-Hill 2010.

Cardiovascular Disease (CVD) Classification Schemas CVD is a class of diseases that involve the heart and/or blood vessels.

CVD can be classified as:  Vascular  Inflammatory/Autoimmune  Anatomic  Degenerative  Traumatic/Emergency  Infectious  Congenital  Neoplastic

Marc Imhotep Cray, M.D.

CVD includes:  CAD such as AP and MI  CVA  Heart failure  Hypertensive heart disease  Rheumatic heart disease  Cardiomyopathy  Arrhythmias  Congenital heart disease  Valvular heart disease  Myocarditis  Aortic aneurysms and dissection  Peripheral Artery Disease(PAD)  Thromboembolic Disease  Venous Thrombosis

Baron SJ and Lee CI. Lange Pathology Flash Cards. New York: McGraw-Hill, 2009..

Marc Imhotep Cray, M.D.

3

Baron SJ and Lee CI. Lange Pathology Flash Cards. New York: McGraw-Hill, 2009..

Marc Imhotep Cray, M.D.

4

Learning Objectives 1. Define and classify arteriosclerosis.

2. List the risk factors and explain the pathogenesis of atherosclerosis and describe the morphology of atheromatous lesions.

3. Enumerate the complications of atherosclerosis.

4. Explain the pathogenesis of essential hypertension and describe the cardiac and vascular pathology and complications that it produces.

5. List the causes of secondary hypertension 6. Compare in a table form between benign and malignant hypertension.

Marc Imhotep Cray, M.D.

5

Learning Objectives (2) 7. Define and classify aneurysms and describe their clinical effects.

8. Define and classify vasculitis.

9. Describe the pathogenesis of vasculitis in general, and pathogenesis, morphology and clinical features of polyarthritis nodosa and giant cell arteritis in particular.

10. List the causes of congestive heart failure and describe its pathogenesis.

11.Tabulate the differences between right vs. left heart failure.

12. Classify ischemic heart disease and describe its pathogenesis.

Marc Imhotep Cray, M.D.

6

Learning Objectives (3) 13. Explain the pathogenesis, morphology, fate, and complications of myocardial infarction.

14. Explain the pathogenesis of acute rheumatic fever and rheumatic heart disease.

15. Describe the morphologic changes of acute and chronic rheumatic heart disease.

16. Define infective endocarditis.

17. Describe the pathogenesis and morphologic changes of acute and subacute infective endocarditis and their cardiac and extra-cardiac complications.

18. Define myocarditis, list its causes and describe its morphology and list its complications.

Marc Imhotep Cray, M.D.

7

Learning Objectives (4) 19. Define and classify congenital heart diseases and describe their pathogenesis.

20. List the causes of pericarditis and describe the morphology of acute and chronic pericarditis.

21. List the tumors of the heart and relate their location and morphology to the clinical features that they produce.

22. Describe the morphology of tumors of blood vessels with emphasis on benign vs malignant.

23. Hemangiomas and Kaposi sarcoma and its various types with their associations.

24. Define primary and secondary varicose veins. List their causes, risk factors, and complications.

Marc Imhotep Cray, M.D.

8

Presentation Topical Outline • Overview of Heart and Vascular Diseases • Normal Heart: Anatomy and Physiology • Atherosclerotic Cardiovascular Disease • Angina Pectoris • Myocardial Infarction • Aortic Aneurysm & Arterial Dissection • Infective Endocarditis • Pericarditis • Myocarditis and ARF & RHD • Neoplasm • Congenital Heart Disease • Cardiomyopathies • Arterial (Hypertension) and Venous Diseases Marc Cray, M.D. • Imhotep Congestive Heart Failure

Overview of Heart and Vascular Diseases

Marc Imhotep Cray, M.D.

10

The Six Principal Mechanisms of Heart Disease Although a wide range of diseases can affect CVS, pathophysiologic pathways that result in a “broken” heart distill down to six principal mechanisms: 1. Failure of the pump 2. Obstruction to flow 3. Regurgitant flow 4. Shunted flow 5. Disorders of cardiac conduction 6. Rupture of the heart or major vessel

Marc Imhotep Cray, M.D.

11

Mechanisms of Heart Disease: 1. Failure of the pump  In most common situation, cardiac muscle contracts weakly and chambers cannot empty properly so-called “systolic dysfunction”  In some cases, muscle cannot relax sufficiently to permit ventricular filling, resulting in diastolic dysfunction

Marc Imhotep Cray, M.D.

12

Mechanisms of Heart Disease: 2. Obstruction to flow  Lesions that prevent valve opening (e.g., calcific aortic valve stenosis) or  Lesions that cause increased ventricular chamber pressures (e.g., systemic hypertension or aortic coarctation) can overwork myocardium which has to pump against the obstruction

Marc Imhotep Cray, M.D.

13

Mechanisms of Heart Disease: 3. Regurgitant flow  Valve pathology that allows backward flow of blood results in increased volume workload and may overwhelm pumping capacity of affected chambers

Marc Imhotep Cray, M.D.

14

Mechanisms of Heart Disease: 4. Shunted flow  Defects (congenital or acquired) that divert blood inappropriately from one chamber to another, or from one vessel to another, lead to pressure and volume overloads

Marc Imhotep Cray, M.D.

15

Mechanisms of Heart Disease: 5. Disorders of cardiac conduction  Uncoordinated cardiac impulses or blocked conduction pathways can cause arrhythmias that slow contractions or prevent effective pumping altogether

Marc Imhotep Cray, M.D.

16

Mechanisms of Heart Disease: 6. Rupture of heart or major vessel  Loss of circulatory continuity (e.g., a gunshot wound through thoracic aorta) may lead to massive blood loss, hypotensive shock, and death

Marc Imhotep Cray, M.D.

17

Heart failure  Heart failure, often referred to as congestive heart failure (CHF), is the common end point for many forms of cardiac disease and typically is a progressive condition with a poor prognosis  In the United States alone, over 5 million individuals are affected, resulting in well over 1 million hospitalizations annually, and a financial burden in excess of $32 billion  Roughly one half of patients die within 5 years of receiving a diagnosis of CHF, and 1 in 9 deaths in the United States include heart failure as a contributory cause

Marc Imhotep Cray, M.D.

18

Vascular diseases  Vascular diseases are responsible for some of the most common and lethal conditions afflicting mankind  Although most clinically significant disorders involve arterial lesions, venous pathologies also can wreak havoc  Vascular disease develops through two principal mechanisms: 1. Narrowing or complete obstruction of vessel lumina, occurring either progressively (e.g., by atherosclerosis) or acutely (e.g., by thrombosis or embolism) 2. Weakening of vessel walls, causing dilation and/or rupture

Marc Imhotep Cray, M.D.

19

Normal Heart: Anatomy and Physiology Essential Normal Heart A&P Videos (Parent Folder)  Location of the heart  Pericardium  Conduction System of the Heart  Control of Heart Rate  Coronary Arteries  The Cardiac Cycle Marc Imhotep Cray, M.D.

20

Normal heart, gross • This is external appearance of a normal heart • Epicardial surface is smooth and glistening • Amount of epicardial fat is usual • Left anterior descending coronary artery extends down from the aortic root to the apex

Marc Imhotep Cray, M.D.

21

Normal tricuspid valve, gross • This is the tricuspid valve • Leaflets and thin and delicate • Just like mitral valve, leaflets have thin chordae tendineae that attach leaflet margins to papillary muscles of ventricular wall below Marc Imhotep Cray, M.D.

22

Normal coronary artery, microscopic • This is a normal coronary artery • Lumen is large, without any narrowing by atheromatous plaque • Muscular arterial wall is of normal proportion

Marc Imhotep Cray, M.D.

23

Normal myocardium, medium power microscopic • This is normal appearance of myocardial fibers in longitudinal section • Note central nuclei and syncytial arrangement of fibers, some of which have pale pink intercalated disks

Marc Imhotep Cray, M.D.

24

Physiologic Principles of Cardiac Output Cardiac Output (CO) • CO is equal product of stroke volume (SV) and heart rate (HR); thus, changes in either SV or HR cause a change in CO • SV is dependent upon contractility, preload, and afterload Contractility (inotropism) • Increases with sympathetic stimulation, increased intracellular calcium concentrations, decreased extracellular sodium concentrations, and administration of digitalis • Decreases with parasympathetic stimulation, heart failure, acidosis, hypoxia, and hypercapnia.

Preload • Preload is ventricular end-diastolic volume and is related to right atrial pressure.

• Increases with increased venous return caused by exercise, blood transfusion, and sympathetic stimulation • Venous dilators (eg, nitroglycerin) work by decreasing preload Marc Imhotep Cray, M.D.

25

Physiologic Principles of CO (2) Afterload • Afterload is diastolic arterial pressure and is proportional to peripheral resistance.

• LV afterload corresponds to aortic pressure and RV afterload corresponds with pulmonary artery pressure.

• Vasodilators (eg, hydralazine) work by decreasing the afterload.

Starling Curve (Illus.)

• Starling curve relates preload (or ventricular end-diastolic) volume with CO (or SV) • It shows that force of contraction is proportional to initial length of cardiac muscle fiber • An increase in preload will cause a corresponding increase in CO

Marc Imhotep Cray, M.D.

First Aid for the USMLE Step1, 2020, Pg.285.

26

Mean arterial pressure (MAP) • Mean arterial pressure (MAP) is determined by how much blood heart pumps into arterial system in a given time (cardiac output [CO]) and how much resistance arteries have to this input (total peripheral resistance [TPR]) • Mathematically, this is expressed as MAP = CO X TPR o Consequently all drugs that lower BP work by affecting either CO or TPR (or both) Important Note: • Primary determinant of SBP is CO, whereas • Primary determinant of DBP is TPR • B/C approximately one third of cardiac cycle is spent in systole and two thirds in diastole, MAP can be calculated as MAP=1/3 SBP + 2/3 DBP Marc Imhotep Cray, M.D.

27

Blood pressure regulation Blood pressure is determined by vascular resistance and cardiac output. Vascular resistance is regulated at the level of the arterioles, influenced by neural and hormonal inputs. Cardiac output is determined by heart rate and stroke volume, SV is strongly influenced by blood volume. Blood volume in turn is regulated mainly by renal sodium excretion or reabsorption.

Renin, a major regulator of BP, is secreted by the kidneys in response to decreased BP in afferent arterioles. In turn, renin cleaves angiotensinogen to angiotensin l; subsequent peripheral catabolism (ACE) produces angiotensin Il, which regulates BP by increasing vascular SMC tone and by increasing adrenal aldosterone secretion, which consequently increases renal sodium reabsorption.

Kumar V; Abbas AK; Aster JC. Robbins Basic Pathology, 10th ed. Philadelphia: Elsevier, 2018; Fig. 10.3, Pg.365.

Marc Imhotep Cray, M.D.

28

Physiology of Blood Vessels Arteries • Thick walled vessels under high pressure that carry stressed volume • Divided into three types: (1) large, elastic arteries (eg, aorta); (2) medium-sized, muscular arteries comprising branches of aorta; and (3) small arteries within tissues and organs • Atherosclerosis affects elastic and muscular arteries Arterioles • Smallest branches of arteries • Principal sites of physiologic blood flow resistance • Site of highest reduction in blood pressure and velocity • Hypertension affects small muscular arteries and arterioles Marc Imhotep Cray, M.D.

29

Physiology of Blood Vessels (2) Capillaries • Arise from arterioles and comprise largest total crosssectional area and surface area in cardiovascular system • Lined by endothelial cells and supported by a thin basement membrane of note, tunica media is absent • Slow flow, high surface area, and thin walls allow rapid exchange of materials betw. blood and tissue.

Veins • Large-caliber, thin-walled vessels under low pressure • Contain highest proportion of blood in cardiovascular system, and carry unstressed volume • Have poor support and are predisposed to compression, dilatation, and invasion by tumors and inflammation

Marc Imhotep Cray, M.D.

30

Structure of Blood Vessels (a) arteries and (b) veins share same general features, but walls of arteries are much thicker b/c of higher pressure of bld that flows through them (c) micrograph shows relative differences in thickness (LM ×160)  Resistance vessels =small arteries, arterioles, and precapillary sphincters  Capacitance vessels =sm. and lg. veins • Have great capacity to distend • For a similar rise in pressure, capacitance vessels may accommodate 20 times more bld than resistance vessels Marc Imhotep Cray, M.D.

https://opentextbc.ca/anatomyandphysiology/chapter/ 20-1-structure-and-function-of-blood-vessels/

Regional vascular specializations. Although all vessels share the same general constituents, the thickness and composition of the various layers differ as a function of hemodynamic forces and tissue requirements

Kumar V; Abbas AK; Aster JC. Robbins Basic Pathology, 10th ed. Philadelphia: Elsevier, 2018; Fig. 10.1, Pg.362.

Marc Imhotep Cray, M.D.

32

Basal and activated endothelial cell states. Normal blood pressure, laminar flow, and stable growth factor levels promote a basal endothelial cell state that maintains a nonthrombotic surface and appropriate vascular wall smooth muscle tone. Injury or exposure to certain mediators results in endothelial activation, a state in which endothelial cells develop adhesive, procoagulant surfaces and release factors that lead to smooth muscle contraction and/or proliferation and matrix synthesis.

Kumar V; Abbas AK; Aster JC. Robbins Basic Pathology, 10th ed. Philadelphia: Elsevier, 2018; Fig. 10.2, Pg.363.

Marc Imhotep Cray, M.D.

33

Endothelial Cell Properties and Functions

34

Marc Imhotep Cray, M.D. Kumar V; Abbas AK; Aster JC. Robbins Basic Pathology, 10th ed. Philadelphia: Elsevier, 2018; Table. 10.1, Pg.3

Vascular Structure and Function Key Points  All vessels are lined by endothelium; although all ECs share certain homeostatic properties, ECs in specific vascular beds have special features that allow for tissue-specific functions (e.g., fenestrated ECs in renal glomeruli)  Relative SMC (smooth muscle cell) and ECM (extracellular matrix) content of vessel walls (e.g., in arteries, veins, and capillaries) varies according to hemodynamic demands (e.g., pressure, pulsatility) and functional requirements  EC function is tightly regulated in both basal and activated states 

Various physiologic and pathophysiologic stimuli induce endothelial activation and dysfunction that alter EC phenotype (e.g., procoagulative versus anti-coagulative, proinflammatory versus anti-inflammatory, nonadhesive versus adhesive)

Marc Imhotep Cray, M.D.

35

Atherosclerotic Cardiovascular Disease

Marc Imhotep Cray, M.D.

36

Clinical Vignette 1 A 40-year-old white man presents to your office complaining of pressure-like chest pains radiating to his shoulder during strenuous physical activities. On further questioning, he indicates that he has painful muscle cramps in his legs when climbing stairs. Both his chest pains and leg cramps are relieved by rest. Family history reveals his father died of an MI in his early 50s and two paternal uncles experienced the same fate. Physical examination is notable for yellow nodules under both eyelids. You send him for laboratory studies including triglyceride and cholesterol levels to confirm your diagnosis.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

37

Atherosclerosis Capsule Very Common: Disease of elastic arteries and large- and medium-sized muscular arteries; a form of arteriosclerosis caused by buildup of cholesterol plaques in intima Location: Abdominal aorta > Coronary artery > Popliteal artery > Carotid artery > circle of Willis.

Risk Factors: Modifiable: smoking, hypertension, dyslipidemia (inc. LDL, dec.

HDL), diabetes; Non-modifiable: age, sex (inc. in men & postmenopausal women), family history Symptoms: Angina, claudication, but can be asymptomatic Progression: Inflammation important in pathogenesis: endothelial cell dysfunction macrophage and LDL accumulation foam cell formation fatty streaks smooth muscle cell migration (involves PDGF and FGF), proliferation, and extracellular matrix deposition fibrous plaque complex atheromas calcification (calcium content correlates with risk of complications) Complications: Aneurysms, ischemia, infarcts, peripheral vascular disease, thrombus, emboli Platelet-derived growth factor (PDGF) Fibroblast growth factor Marc Imhotep Cray, M.D.(FGF)

38

Atherosclerosis  Etiology:  Risk factors include smoking, HTN, diabetes, hypercholesterolemia (increased LDL), positive family history, old age, male gender, postmenopausal status in women, hyperuricemia, and oral contraceptive use

 Pathology:  Artery: Progresses from fatty streaks (lipid-laden foam cell accumulations in intima) to proliferative plaques to complex atheromas  Atheroma: Central core of cholesterol and foam cells (lipid-laden macrophages) covered by fibrous cap o atheromas may be complicated by overlying thrombus formation, ulceration, or calcification of plaque; o usually present in elastic arteries and medium/large muscular arteries Marc Imhotep Cray, M.D.

39

Atherosclerosis (2) Clinical Manifestations: Often asymptomatic; can present w angina or claudication (pain in muscles during exercise, relieved by rest)  Complications include aneurysms, MI, stroke, bowel ischemia, renal artery ischemia, peripheral vascular occlusive disease, and emboli of overlying thrombus or of plaque itself

Treatment: Lipid-lowering agents (eg, HMG-CoA reductase inhibitor)=Statins Note: Xanthomas are yellow plaques or nodules of skin composed of lipid-laden macrophages and are assoc. w hypercholesterolemia Marc Imhotep Cray, M.D.

40

Arteriosclerosis Arteriosclerosis is a general term for several disorders that cause thickening and loss of elasticity in the arterial wall  Atherosclerosis, the most common form, is also most serious b/c it causes coronary artery disease and cerebrovascular disease

Coronary artery with atherosclerotic narrowing, microscopic

Atherosclerosis is patchy intimal plaques (atheromas) in medium-sized and large arteries  Plaques contain lipids, inflammatory cells, smooth muscle cells, and connective tissue 41 Marc Imhotep Cray, M.D.

Marc Imhotep Cray, M.D.

42

Atherosclerosis Pathogenesis

First Aid for the USMLE Step1 , 2020, Pg.302.

Endothelial cell injury → macrophages/platelets adhere to damaged endothelium and release cytokines → smooth muscle hyperplasia/migration of cells to the tunica intima → macrophages form foam cells plus smooth muscle → fibrous cap develops → fibrous cap (plaque) calcifies dystrophically and ulcerates → platelets adhere to the ulcer, causing vessel thrombosis

Marc Imhotep Cray, M.D.

43

Atherosclerosis Pathogenesis (2)

First Aid for the Basic Sciences- Organ Systems, Pg. 47.

Marc Imhotep Cray, M.D.

44

Pathobiology of Atherosclerosis GROSS/MICRO BIOLOGY  Fatty streaks are flat and yellow and on microscopy contain foam cells (lipid-laden macrophages)

Fibrous plaque.

 Fibrous plaques are elevated white plaques that contain a necrotic core of cholesterol, lipids, foam cells, and debris surrounded by a fibrous cap of collagen, smooth muscle, and lymphocytes COMPLICATIONS  Plaque rupture unstable angina, MI, death, stroke, aneurysm formation due to artery wall degeneration, TIAs, renal artery ischemia, peripheral vascular occlusive disease (PVD), impotence, claudication, proximal renal thrombosis → RAAS activation and hypertension Marc Imhotep Cray, M.D.

First Aid for the Basic Sciences- Organ Systems, Pg. 47.

45

Atherosclerosis Complication (MI) and LAD coronary artery w recent thrombus  Symptoms develop when Heart  Anterior surface of heart demonstrates an opened left anterior descending coronary artery growth or rupture of plaque  Within lumen of coronary can be seen a dark red recent coronary thrombosis reduces or obstructs blood  Dull red color to myocardium as seen below glistening flow epicardium to lower right of thrombus is consistent with underlying myocardial infarction

 Diagnosis is clinical and confirmed by angiography, ultrasonography, or other imaging tests  Treatment includes risk factor and dietary, modification, physical activity, antiplatelet drugs, and antiatherogenic drugs Marc Imhotep Cray, M.D.

46

Risk Factors for Atherosclerosis Risk factors are divided into major and minor categories:  Major: Hyperlipidemia, hypertension, smoking, diabetes, and obesity  Minor: Male gender, oral contraceptives / decreased estrogen (Postmenopausal), increased age, sedentary lifestyle, stress, elevated homocysteine level, family history, and infections (Chlamydia pneumoniae) [See https://www.nature.com/articles/nrmicro796]

Marc Imhotep Cray, M.D.

47

Coronary artery with atherosclerotic narrowing, microscopic • Coronary artery shown here has narrowing of lumen due to build up of atherosclerotic plaque • Severe narrowing can lead to angina, ischemia, and infarction

Marc Imhotep Cray, M.D.

48

Coronary artery with recanalized thrombosis, microscopic • This section of coronary artery demonstrates remote thrombosis w recanalization to leave only two small, narrow channels

Marc Imhotep Cray, M.D.

49

Coronary artery with calcific atherosclerosis, microscopic • There is a severe degree of narrowing in this coronary artery • It is "complex" in that there is a large area of calcification on lower right, which appears bluish on this H&E stain • Complex atheroma have calcification, thrombosis, or hemorrhage • Such calcification would make coronary angioplasty difficult Marc Imhotep Cray, M.D.

50

Aortas demonstrating various degrees of atherosclerosis, gross • These three aortas demonstrate mild, moderate, and severe atherosclerosis from bottom to top • At bottom, mild atherosclerosis shows only scattered lipid plaques • Aorta in middle shows many more larger plaques • Severe atherosclerosis in aorta at top shows extensive ulceration in plaques Marc Imhotep Cray, M.D.

51

Diagnostic Classifications of CAD  Anatomic (Pathologic) Dx= Atherosclerosis (ASHD)  Etiologic Dx= Coronary Heart Disease (CHD, IHD, CAD)  Physiologic Dx=AP, Arrhythmia MI, SCD, Related arterial diseases, Over time CAD can lead to heart failure  Functional Dx= Stable vs Unstable Angina vs ACS

Marc Imhotep Cray, M.D.

52

Coronary heart disease (CHD) Defined (Etiologic Dx)  Coronary heart disease (CHD) is a condition in which proper circulation of blood and oxygen are not provided to heart and surrounding tissue  Result is due to a narrowing of small blood vessels, which normally supply heart w blood and oxygen  CHD, one type of cardiovascular disease, is leading cause of death for both men and women in United States

Marc Imhotep Cray, M.D.

53

Causes (Anatomic Dx) 

The typical cause of CHD is atherosclerosis, which takes place w plaque and fatty build up on artery walls, narrowing the vessels

Marc Imhotep Cray, M.D.

54

Schematic for causes and outcomes of ischemic heart disease (IHD) showing interrelationships among:  Coronary artery disease (CAD),  Acute plaque change,  Myocardial ischemia,  Myocardial infarction(MI),  Chronic IHD,  congestive heart failure (CHF), and  Sudden cardiac death (SCD)

Marc Imhotep Cray, M.D.

Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease, 9th ed. Philadelphia: Saunders, 2015, Fig. 12-19, p 550.

55

Coronary artery, mild atherosclerosis, gross • A coronary artery has been opened longitudinally • Coronary extends from left to right across middle of picture and is surrounded by epicardial fat • Increased epicardial fat correlates with increasing total body fat • There is a lot of fat here, suggesting one risk factor for atherosclerosis • This coronary shows only mild atherosclerosis, with only an occasional yellow-tan lipid plaque and no narrowing Marc Imhotep Cray, M.D.

56

Coronary artery, severe atherosclerosis, gross • This is left coronary artery from aortic root on left • Extending across middle of picture to right is anterior descending branch • This coronary shows severe atherosclerosis w extensive calcification • At far right, there is an area of significant narrowing

Marc Imhotep Cray, M.D.

57

Coronary artery, hemorrhage into plaque, gross •

•

Coronary atherosclerosis with complication of hemorrhage into atheromatous plaque, seen here in center of photograph Such hemorrhage acutely may narrow arterial lumen

Marc Imhotep Cray, M.D.

58

Heart and LAD coronary artery with recent thrombus, gross • Anterior surface of heart demonstrates an opened left anterior descending coronary artery • Within lumen of coronary can be seen a dark red recent coronary thrombosis • Dull red color to myocardium as seen below glistening epicardium to lower right of thrombus is consistent with underlying myocardial infarction Marc Imhotep Cray, M.D.

59

Angina Pectoris

Marc Imhotep Cray, M.D.

60

Clinical Vignette 2 During a routine physical examination, a 60-year-old man mentions to you that he occasionally experiences chest discomfort that radiates to his left shoulder. He describes that discomfort as a “weight on his chest” and notes that the pain tends to come on after he shovels his driveway and dissipates with rest. He denies any chest pain at rest. You schedule him for an exercise stress test, write him a prescription for nitroglycerin, and warn him against performing any strenuous exercise until further consultation with a cardiologist.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

61

Angina Pectoris (AP)  Etiology:  Stable angina: Caused by atherosclerosis  Prinzmetal (variant) angina: Associated with coronary artery vasospasm  Unstable (crescendo) angina: Caused by disruption of atherosclerotic plaque w partial thrombosis in coronary artery o angina pectoris that is irregular o classified as a type of acute coronary syndrome (ACS) o difficult to distinguish unstable angina from non-ST elevation (non-Q wave) myocardial infarction (NSTEMI)

 Pathophysiology: All types of angina are caused by transient ischemia resulting in inadequate myocardial oxygenation Marc Imhotep Cray, M.D.

62

Angina Pectoris (2) Clinical Manifestations:  Stable: Precordial chest discomfort associated w exertion; pain is relieved by rest and nitroglycerin; nonspecific ST-T changes on ECG  Prinzmetal: Episodic chest pain occurring at rest; may see ST elevation on ECG  Unstable: Progressively frequent chest pain initially occurring with activity but later occurring at rest; considered indication for acute MI in near future; may see ST depressions on ECG Marc Imhotep Cray, M.D.

63

Angina Pectoris (3) Treatment:  Stable: Nitrates; β-blockers; statins; aspirin  Prinzmetal: Vasodilators (nitrates, calcium channel blockers [CCBs])  Unstable: β-blockers; statins; aspirin; coronary evaluation w catheterization in near future; consider heparin treatment

Of note: Angina pectoris may be clinically silent in diabetics

Marc Imhotep Cray, M.D.

64

Angina Pectoris Overview Angina, or angina pectoris (AP), is a gripping (vice-like or pressure-like) pain felt in the center of the chest that may radiate to the neck, jaw, and arms and is caused most often by exercise; emotion, eating, and cold weather are other causes

Marc Imhotep Cray, M.D.

65

CAD Risk Factors Certain conditions are considered to put an individual at greater risk for coronary heart disease The following are some risk factors: (same as for atherosclerosis in general)

 Diabetes  High blood pressure  High bad cholesterol (LDL)  Smoking  Genetics (heredity)  Age (particularly 50+)  Increased levels of C-reactive protein, fibrinogen, or homocysteine  Lack of sufficient physical activity  Low good cholesterol (HDL)  Menopause  Obesity Marc Imhotep Cray, M.D.

66

Angina Pectoris (Chest Pain) • When supply of O2 and nutrients in bld is insufficient to meet demands of heart heart muscle “cries out in pain” • Heart demands a large supply of oxygen to meet demands placed on it • In CAD patients demands on the heart require O2 supply that can’t be meant

Marc Imhotep Cray, M.D.

67

 Angina, or angina pectoris, is a gripping pain felt in chest that may move to neck, jaw, and arms and is caused most often by exercise; emotion, eating, and cold weather are other causes  AP occurs when heart receives deficient oxygen b/c of blood vessel narrowing, which results mainly from atherosclerosis due to aging , cigarette smoking, HTN, high cholesterol levels, obesity, and diabetes Marc Imhotep Cray, M.D.

Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated Edition. Philadelphia: Sanders, 2014.

68

Diagnosis DX of CHD may be accomplished by a variety of means: Coronary angiography Coronary arteriography Coronary CT angiography Echocardiogram Electrocardiogram (ECG) Electron-beam CT (EBCT) Exercise stress test Magnetic resonance angiography Nuclear scan Marc Imhotep Cray, M.D.

69

Treatment Coronary heart disease treatment methods may include: (depends on presenting Physiologic Dx) 1. Angioplasty with stenting 2. Coronary artery bypass surgery (CABG) 3. Medication 4. Minimally invasive heart surgery 5. Proper diet and exercise 6. Quitting smoking 7. Treatment of other comorbidities, HTN, DM, Obesity, LDL

Marc Imhotep Cray, M.D.

70

Myocardial Infarction

Marc Imhotep Cray, M.D.

71

Clinical Vignette 3 A 60-year-old man presents to the emergency department complaining of 2 hours of crushing substernal chest pain that radiates to his left shoulder and jaw. He appears fatigued and is breathing heavily and sweating profusely. You order an ECG, which demonstrates ST elevations across the precordium. You immediately activate the cardiac catheterization laboratory in the hopes of minimizing tissue damage caused by his condition. You worry that this patient may be at significant risk for ventricular rupture in 5–7 days What is the Diagnosis?

Marc Imhotep Cray, M.D.

72

Myocardial Infarction Etiology: Caused by vasospasm, embolus, or atherosclerotic thrombus resulting in coronary artery occlusion  Risk factors include increasing age, hypertension, smoking, diabetes, male gender, postmenopausal women, and hyperlipidemia Pathology  Heart: Progression from wavy fibers w edema and hemorrhage (4-12 hours) to coagulative necrosis w muscle hypereosinophilia and neutrophilic infiltration (12-36 hours) to macrophage infiltration w phagocytosis of dead cells and formation of granulation tissue (5-10 days) to scar formation (10 days to 2 months) (See USMLE Step 1 First Aid, 2020, Pgs. 305-7) Marc Imhotep Cray, M.D.

73

Myocardial Infarction (2) Clinical Manifestations: Crushing, substernal chest pain with radiation to jaw and left arm; dyspnea; nausea; diaphoresis  Complications: include cardiac arrhythmia (can cause sudden death within first few days), fibrinous pericarditis (within 3-5 days), pulmonary edema, CHF, shock, thromboembolism, rupture of ventricular free wall or septum (VSD) (within 7-10 days), rupture of papillary muscle leading to mitral regurgitation, and Dressler syndrome (autoimmune fibrinous pericarditis several weeks post-MI)  Lab findings: Diagnosis with ST elevation (STEMI) and permanent Q wave on ECG (within hours); elevated cardiac troponin (seen within 4 hours to 10 days); elevated CK-MB, LDH-1, and AST

 Tx: Thrombolytic therapy and/or coronary angioplasty for early MI

Marc Imhotep Cray, M.D.

74

Cardiac and vascular function curves: MI causes decrease contractility (Inotropy)

First Aid for the USMLE Step1 , 2020, Pg.289.

 Inotropy: Changes in contractility altered SV altered CO/VR and RA pressure (RAP)  Catecholamines, digoxin, exercise ⊕  HF w reduced EF, narcotic overdose, sympathetic inhibition ⊝ To learn more see: Ppt. Presentation, Relationships Betw. CO and VR Marc Imhotep Cray, M.D.

75

Heart, left ventricle, acute myocardial infarction, gross • This is left ventricular wall which has been sectioned lengthwise to reveal a large recent myocardial infarction • Center of infarct contains necrotic muscle that appears yellow-tan • Surrounding this is a zone of red hyperemia • Remaining viable myocardium is reddish- brown

Marc Imhotep Cray, M.D.

76

Heart, left ventricle and septum, myocardial infarction, gross • This cross section through heart demonstrates left ventricle on left • Extending from anterior portion and into septum is a large recent myocardial infarction • Center is tan with surrounding hyperemia • Infarction is "transmural" in that it extends through full thickness of wall

Marc Imhotep Cray, M.D.

77

Heart, transmural myocardial infarction with rupture and hemopericardium, gross • One complication of a transmural myocardial infarction is rupture of myocardium • This is most likely to occur in first week between 3 to 5 days following initial event, when myocardium is softest • White arrow marks point of rupture in this anterior-inferior myocardial infarction of left ventricular free wall and septum • Note dark red blood clot forming hemopericardium can lead to tamponade Marc Imhotep Cray, M.D.

78

Heart, left ventricular aneurysm, gross • A cross section through heart reveals a ventricular aneurysm with a very thin wall at arrow • Note how aneurysm bulges out • Stasis in this aneurysm allows mural thrombus, which is present here, to form within aneurysm

Marc Imhotep Cray, M.D.

79

How it Works Book of the Human Body, Sixth Edition. Imagine Publishing Ltd, 2016.

Learn more: Myocardial infarction_ Causes, Symptoms, Diagnosis, Treatment, and Pathology. Dr. Cray Ppt. Presentation Marc Imhotep Cray, M.D.

80

How it Works Book of the Human Body, Sixth Edition. Imagine Publishing Ltd, 2016.

Marc Imhotep Cray, M.D.

81

Aortic Aneurysm and Arterial Dissection

Marc Imhotep Cray, M.D.

82

Aortic aneurysm  

Localized pathologic dilation of aorta May cause abdominal and/or back pain, which is a sign of leaking, dissection, or imminent rupture

Marc Imhotep Cray, M.D.

83

Abdominal aortic aneurysm  Usually assoc. w atherosclerosis  Risk factors include history of tobacco use, inc. age, male sex, family history  May present as palpable pulsatile abdominal mass  Most often infrarenal (distal to origin of renal arteries) CT Scan (arrows point to outer dilated calcified aortic wall, with partial crescentshaped non-opacification of aorta due to flap/ clot)

Marc Imhotep Cray, M.D.

84

Aorta, atherosclerotic aneurysm, gross • Here is an example of an atherosclerotic aneurysm of aorta in which a large "bulge" appears just above aortic bifurcation • Such aneurysms are prone to rupture when they reach 6 to 7 cm in size • They may be felt on PE as a pulsatile mass in abdomen • Most are located below renal arteries so that surgical resection can be performed w placement of a dacron graft

Marc Imhotep Cray, M.D.

85

Thoracic aortic aneurysm  Assoc. w cystic medial degeneration (necrosis)  Risk factors include hypertension, bicuspid aortic valve, connective tissue disease (eg, Marfan syndrome)  Also assoc. w 3° syphilis (obliterative endarteritis of vasa vasorum)  Aortic root dilatation may lead to aortic valve regurgitation Marc Imhotep Cray, M.D.

A contrast enhanced CT showing a large thoracic aneurysm of about 7 cm which has ruptured

Black arrow is aorta, white arrow is bld in thorax

86

Abdominal aortic aneurysm, CT scan with contrast • This abdominal high speed CT scan w contrast demonstrates an AAA approx. 6 cm in diameter • At this size, there is increased risk for rupture

Clinical: Master of Surgery Video_Abdominal Aortic Aneurysm Repair Marc Imhotep Cray, M.D.

87

Clinical Vignette 4 A 30-year-old man with Marfan syndrome presents to the emergency room with severe, sudden, tearing chest pain radiating to the abdomen and back. The pain has progressively shifted downward over the last several hours.

On physical examination, he is found to have asymmetric pulses and a pericardial friction rub. ECG studies are normal and angiography shows an ascending aortic abnormality. You schedule the patient for immediate surgical repair.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

88

Aortic Dissection  Etiology: Associated with hypertension, trauma, Marfan syndrome, Ehlers-Danlos syndrome*, coarctation of the aorta, bicuspid aortic valve, and last trimester of pregnancy; there is no (direct) assoc. with atherosclerosis  Pathology:  Gross: Tear in aortic intima allowing formation of intramural hematoma; possible presence of cystic medial necrosis (lesion predisposing to aortic dissection characterized by separation of elastic and muscular elements of media) *Ehlers–Danlos syndromes (EDS) are a group of genetic connective tissue disorders; Symptoms may include loose joints, joint pain, stretchy velvety skin, and abnormal scar formation; Can be noticed at birth or early childhood; Complications may include aortic dissection, joint dislocations, scoliosis, chronic pain, or early osteoarthritis.

Marc Imhotep Cray, M.D.

89

Types of Aortic Dissection Two types: Stanford type A (proximal): involves ascending aorta  May extend to aortic arch or descending aorta  May result in acute aortic regurgitation or cardiac tamponade Stanford type B (distal): involves only descending aorta (Below left subclavian artery)

Marc Imhotep Cray, M.D.

First Aid for the USMLE Step1 , 2020, Pg.303.

90

Osmosis Aortic Dissection video graphic capture 1

Marc Imhotep Cray, M.D.

91

Osmosis Aortic Dissection video graphic capture 2

Marc Imhotep Cray, M.D.

92

Aortic Dissection cont’ed. Clinical Manifestations: Presents with sudden, severe, tearing left chest pain, often radiating through back; pain shifts downward with time  Complications include aortic rupture causing hemopericardium, cardiac tamponade, and death Treatment: Stanford type A Surgical repair if dissection involves ascending aorta or if there is significant branch artery involvement; Stanford type B Strict HR and BP control with β-blockers, and vasodilators or CCBs Marc Imhotep Cray, M.D.

93

Aorta, dissection with tear in arch, gross • There is a tear (arrow) located 7 cm above aortic valve and proximal to great vessels in this aorta with marked atherosclerosis • This is an aortic dissection

Marc Imhotep Cray, M.D.

94

Hemopericardium with cardiac tamponade, gross • An aortic dissection may lead to hemopericardium when blood dissects through media proximally • Such a massive amount of hemorrhage leads to cardiac tamponade (prevents heart from filling properly in diastole) • Presents w dyspnea and tachypnea PE Beck's triad = distended neck veins, hypotension, distant heart sounds, and pulsus paradoxus (drop in systolic blood pressure ≥10 mm Hg on inspiration) Marc Imhotep Cray, M.D.

95

Aorta, dissection, gross • This aorta has been opened longitudinally to reveal an area of fairly limited dissection that is organizing • The red-brown thrombus can be seen in on both sides of section as it extends around aorta • Intimal tear would have been at left • This creates a "double lumen" to aorta • This aorta shows severe atherosclerosis which, along with cystic medial necrosis and hypertension, is a risk factor for dissection Marc Imhotep Cray, M.D.

96

Aorta, dissection, microscopic • Here, dissection went into muscular wall • Aortic dissection is an extreme emergency and can lead to death in a matter of minutes • Blood can dissect up or down aorta • Blood dissecting up around great vessels can close off carotids • Blood can dissect down to coronaries and shut them off Marc Imhotep Cray, M.D.

97

Carotid artery, dissection with compression, gross • Right carotid artery is compressed by blood dissecting upward from a tear with aortic dissection • Blood may also dissect to coronary arteries thus pts. w AD may have Sx of severe chest pain (for distal dissection) or may present with findings that suggest a stroke (w carotid dissection) or myocardial ischemia (w coronary dissection)

Marc Imhotep Cray, M.D.

98

Infective Endocarditis

Marc Imhotep Cray, M.D.

99

Clinical Vignette 5 A 30-year-old man presents to the emergency room with sudden high fever and shaking chills. A new murmur localized to the mitral valve is heard. The patient has bilateral nail-bed hemorrhages, painful nodules on the tips of his fingers and toes, an erythematous rash on his palms and soles, and white spots surrounded by hemorrhage in his retina. You immediately begin the patient on broad spectrum antibiotics and order blood cultures and an echocardiogram to confirm the diagnosis.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

100

Acute and Subacute Endocarditis  Etiology:  Acute: Often caused by Staphylococcus aureus  Subacute: Often caused by viridians streptococci (eg, S mutans); often occurs after dental procedures  Pathology:  Acute: Large vegetations consisting of fibrin, inflammatory cells, and bacteria on previously normal valves  Subacute: Small vegetations consisting of fibrin, chronic inflammatory cells, and fibrosis on abnormal valves (mitral and aortic)

Marc Imhotep Cray, M.D.

101

Acute and Subacute Endocarditis (2) Clinical Manifestations:  Acute: Sudden high fever with chills; new onset of murmur  Subacute: Insidious onset with low-grade fever  Both types can present w Osler nodes (painful nodules on digit pads), Janeway lesions (red rash on palms and soles), Roth spots (white spots on retina with surrounding hemorrhage), nail-bed splinter hemorrhages, and bacteremia  Complications include chordae tendineae rupture, perforation of valvular leaflet, heart failure, suppurative pericarditis, and septic emboli Marc Imhotep Cray, M.D.

102

Acute and Subacute Endocarditis (2) Treatment:  Acute: Broad spectrum antibiotics; may need surgical treatment if severe  Subacute: Broad spectrum antibiotics; prophylaxis of SBE with antibiotics in susceptible individuals before dental procedures Note:  Tricuspid valve endocarditis is assoc. w IV drug use  Nonbacterial thrombotic endocarditis (NBTE or marantic endocarditis) is assoc. w sterile emboli and seen w cancer metastasis or renal failure, SLE (Libman-Sacks endocarditis) [which demonstrates vegetation on both sides of valve] , DIC, or carcinoid syndrome Marc Imhotep Cray, M.D.

103

Aortic valve, infective endocarditis, gross • This is infective endocarditis • Aortic valve demonstrates a large, irregular, reddish tan vegetation • Virulent organisms, such as Staphylococcus aureus, produce an "acute" bacterial endocarditis, • While some organisms such as Streptococcus viridans produce a "subacute" bacterial endocarditis

Marc Imhotep Cray, M.D.

104

Infective endocarditis spreading to myocardium, gross • In this case, infective endocarditis demonstrates how infection tends to spread from valve surface • Here, vegetations can be seen on endocardial surfaces, and infection is extending into to underlying myocardium Marc Imhotep Cray, M.D.

105

Infective endocarditis, microscopic • Microscopically, valve in infective endocarditis demonstrates friable vegetations of fibrin and platelets (pink) mixed with inflammatory cells and bacterial colonies (blue) • Friability explains how portions of vegetation can break off and embolize Marc Imhotep Cray, M.D.

106

Heart, microabscesses, gross The epicardial surface of the heart is smooth and glistening, but there are small scattered pinpoint yellowish microabscesses (Higher magnification in next photo).

Marc Imhotep Cray, M.D.

107

Heart, microabscess, gross • This magnification of the preceding photograph shows the small yellowish pinpoint microabscesses on the epicardial surface • Microabscesses may appear in persons who are septic • They may also represent emboli from an infective endocarditis in which small portions of a vegetation have embolized out coronary arteries Marc Imhotep Cray, M.D.

108

Heart, microabscess, microscopic • Microscopic appearance of a microabscess is shown here • Center consists of blue bacterial colonies and is surrounded by acute inflammatory cells

Marc Imhotep Cray, M.D.

109

Pericarditis

Marc Imhotep Cray, M.D.

110

Clinical Vignette 6 A 35-year-old woman presents with acute chest pain and a nonproductive cough. Review of systems reveals a history of malar rash, fatigue, and migratory polyarthritis. On physical examination, she is found to have a friction rub and distant heart sounds and she complains of increased pain when supine. An increased jugular venous pressure is noted with inspiration and diffuse ST elevations are seen on most ECG leads. You initiate therapy with corticosteroids and refer her to a rheumatologist and a cardiologist.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

111

Heart Wall Layer Anatomical Relationships, Including Pericardium

Pericardium Anatomy Explained _Video Marc Imhotep Cray, M.D.

112

Pericarditis  Etiology:  Acute: o Can be serous (caused by SLE, RA, scleroderma, renal failure, viral infection, or tumors), o fibrinous (caused by renal failure, MI, ARF, radiation, or postsurgical trauma), o hemorrhagic (caused by TB or malignancy), or o suppurative (caused by bacteria such as TB, Staphylococcus, or Pneumococcus)  Constrictive (Chronic): Previous history of acute pericarditis

Marc Imhotep Cray, M.D.

113

Pericarditis (2) Pathology and Pathophysiology:  Acute: (1)Serous: protein-rich exudate in pericardial space w inflammatory rxn on tissue surfaces; (2)Fibrinous: fibrin-rich exudate in pericardial space, which may resolve or organize into scar; (3)Suppurative: purulent exudate w massive inflammatory rxns on tissue surfaces, which usually organizes into scar; (4)Hemorrhagic: fibrin-rich exudate w assoc. hemorrhage in pericardial space

 Constrictive: Heart encased by fibrous scar w loss of pericardial space reduced cardiac contraction and venous return Marc Imhotep Cray, M.D.

114

Pericarditis (3)  Clinical Manifestations:  Acute: Chest pain worsening w inspiration and supine position; friction rub; pulsus paradoxus; distant heart sounds; fever; nonproductive cough; Kussmaul sign (increased JVP with inspiration) Lab findings: Diffuse ST elevations in most ECG leads and normal CK-MB  Constrictive: Quiet heart sounds; Kussmaul sign; S3; may mimic right-sided heart failure  Treatment:  Acute: Treat any underlying causes if known; NSAIDs; corticosteroids if necessary  Constrictive: Pericardiectomy Marc Imhotep Cray, M.D.

115

Fibrinous pericarditis, gross • A window of adherent pericardium has been opened to reveal surface of heart • There are thin strands of fibrinous exudate that extend from epicardial surface to pericarial sac • This is typical for a fibrinous pericarditis Marc Imhotep Cray, M.D.

116

Hemorrhagic pericarditis, gross • Pericarditis here not only has fibrin, but also hemorrhage thus, this is called a "hemorrhagic pericarditis"

• It is really just fibrinous pericarditis with hemorrhage • Without inflammation, blood in the pericardial sac would be called "hemopericardium”

Marc Imhotep Cray, M.D.

117

Check-Up Question (UWorld, 2015. Cardiology / Pathology # 36):

A 34-year-old Caucasian male presents to the emergency department with recent-onset dyspnea and fatigue. There is no significant past medical history except for a mild respiratory illness one week ago. His blood pressure is 80/60 mmHg. His pulse is 120 beats per minute, regular, but weak. The pulse becomes undetectable to palpation during each inspiration.

The jugular veins are distended The lungs are clear to auscultation. Which of the following do you most suspect in this patent?

A. Acute fibrinous pericarditis B. Acute myocardial infarction C. Septic shock D. Constrictive pericarditis E. Cardiac tamponade F. Tension pneumothorax Marc Imhotep Cray, M.D.

118

Explanation: Jugular venous distension (JVD) is key here. JVD indicates that there is elevation central venous pressure (CVP) in the superior vena cava. The combination of acute-onset CVP elevation (>15 cm H20) with hypotension and tachycardia can occur with cardiac tamponade or tension pneumothorax. No history of chest trauma and no abnormalities on lung auscultation make tension pneumothorax is unlikely. Given the history of an antecedent respiratory illness, the most likely diagnosis is cardiac tamponade due to a serous viral pericarditis and a significant acute pericardial effusion.

NB: Observation of Beck's triad on PE hypotension, distended neck veins, and distant or muffled heart sounds on auscultation - as well as tachycardia, are together indicative of tamponade.

Marc Imhotep Cray, M.D.

119

Myocarditis and Acute Rheumatic Fever & Rheumatic Heart Disease Marc Imhotep Cray, M.D.

120

Clinical Vignette 7 A 20-year-old man from Panama presents to your clinic complaining of dyspnea, orthopnea, bilateral leg swelling, and a bloated belly. He denies any history of a congenital heart disease, rheumatic fever, or valvular disease. As you prepare to admit him to the hospital for further testing and treatment, you wonder if a parasitic disease may be causing his condition.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

121

Myocarditis  Etiology and Epidemiology: Usually caused by viruses (ie, Coxsackievirus A, Coxsackievirus B), or Trypanosoma cruzi (Chagas disease); other causes include fungi (eg, Candida), helminthes (eg, trichinosis), parasites (eg, toxoplasmosis), bacteria (eg, Lyme disease), postviral syndrome, SLE, drug hypersensitivity, hyper/hypothyroidism, and sarcoidosis  Seen most commonly in young men  Pathology:  Gross: Hemorrhages visible on ventricular myocardium  Microscopic: Diffuse myocardial degeneration and necrosis with mononuclear inflammatory infiltrate

Marc Imhotep Cray, M.D.

122

Myocarditis (2)  Clinical Manifestations: May be asymptomatic or may present as biventricular heart failure, fever, dyspnea, fatigue, new onset of systolic murmur, palpitations, or pleuropericardial pain Complications include arrhythmias or sudden death  Treatment: Usually supportive

Marc Imhotep Cray, M.D.

123

Interstitial viral myocarditis, microscopic • Interstitial lymphocytic infiltrates shown here are characteristic for a viral myocarditis=most common type of myocarditis • Many of these cases are probably subclinical • Some may be a cause for sudden death in young persons • Most common viral agent is Coxsackie B

Marc Imhotep Cray, M.D.

124

Clinical Vignette 8 A 10-year-old girl presents to the clinic with fever, malaise, migratory polyarthritis, and a blanching erythematous ringshaped rash over her proximal extremities. On further questioning, you find out that she suffered from a severe sore throat 2 to 3 weeks ago. Serum studies demonstrate an ESR of 100 and a positive anti–streptolysin O titer. You worry that she may suffer from valvular heart disease during her adult years as a result of her current condition.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

125

Acute Rheumatic Fever and Rheumatic Heart Disease  Etiology:  Acute rheumatic fever (ARF): Antibodies formed against group A β-hemolytic streptococci cross-react against patient’s tissues; usually presents in children 5-15 years of age  Rheumatic heart disease (RHD): Late sequelae of acute rheumatic fever; presents 20+ years after ARF  Pathology:  ARF: Presence of Aschoff bodies (inflammatory foci surrounded by lymphocytes) and Anitschkow cells (macrophages which may become multinucleated) producing a pancarditis in heart tissue; serofibrinous pericardial exudate  RHD: Mitral stenosis with fish-mouth deformity; may also 126 affect Marc Imhotep Cray, M.D.aortic valve

ARF and RHD (2) Clinical Manifestations:  ARF: Onset of symptoms 2-3 weeks after streptococcal pharyngitis; major Jones criteria include carditis, migratory polyarthritis, chorea, erythema marginatum (blanching, ring-shaped rash), and subcutaneous nodules; minor Jones criteria include fever, arthralgia, or evidence of previous streptococcal infection (positive anti–streptolysin O [ASO] titer) Lab findings: Elevated ESR  RHD: Presents with valvular heart disease (usually mitral stenosis, but aortic stenosis as well); valvular disease may lead to hypertrophy of heart, arrhythmias, and HF Treatment: Penicillin for streptococcal infection; salicylates for fever and arthritis; endocarditis prophylaxis if indicated127

Marc Imhotep Cray, M.D.

Acute rheumatic carditis, microscopic (1) • Microscopically, acute rheumatic carditis is marked by a peculiar form of granulomatous inflammation with so-called "Aschoff nodules" seen best in myocardium • These are centered in interstitium around vessels as shown here • The myocarditis may be severe enough to cause congestive heart failure Marc Imhotep Cray, M.D.

128

Acute rheumatic carditis, micro. (2) • Here is an Aschoff nodule at high magnification • Most characteristic component is the Aschoff giant cell • Several appear here as large cells with two or more nuclei that have prominent nucleoli • Scattered inflammatory cells accompany them and can be mononuclears or occasionally neutrophils Marc Imhotep Cray, M.D.

129

Acute rheumatic carditis, micro. (3) • Another cell seen w acute rheumatic carditis is Anitschkow cell (myocyte) • This is a long, thin cell with an elongated nucleus

Marc Imhotep Cray, M.D.

130

Chronic rheumatic valvulitis, gross • In time, chronic rheumatic valvulitis may develop by organization of acute endocardial inflammation along with fibrosis, as shown here affecting the mitral valve • Note shortened and thickened chordae tendineae

Marc Imhotep Cray, M.D.

131

Neoplasia

Marc Imhotep Cray, M.D.

132

Clinical Vignette 9 A 40-year-old woman presents to the emergency room complaining of dyspnea on exertion and fainting spells.

Physical examination is significant for a low-grade fever and a regurgitant murmur localized in the left atrium near the mitral valve. Two-dimensional echocardiography shows a tumor near the mitral valve that moves with the cardiac cycle. You schedule surgery to excise the lesion.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

133

Cardiac Neoplasms (Atrial Myxoma and Rhabdomyoma) Etiology and Epidemiology:  Myxomas: Etiology unknown although 10% of cases are caused by autosomal dominant trait; seen in adults  Rhabdomyomas: Associated with tuberous sclerosis; seen in infants and young children Pathology:  Myxoma: Usually found in LA near fossa ovalis; often in pedunculated form; composed of globular myxoma cells and smooth muscle cells in a mucopolysaccharide ground substance  Rhabdomyoma: Grayish myocardial mass that protrudes into ventricle; composed of spider cells (polygonal cells w glycogen-laden vacuoles separated by cytoplasmic 134 strands) Marc Imhotep Cray, M.D.

Cardiac Neoplasms (2) Clinical Manifestations:  Myxoma: Presents when mitral valve function is compromised by ball-valve obstruction causing dyspnea or syncope, when a stroke occurs b/c of an embolus, or when a regurgitant valvular murmur is found on physical examination; systemic manifestations includes fever, wasting, arthralgias, malaise, and anemia  Rhabdomyoma: Presents with symptoms of obstruction of cardiac chamber Treatment: Myxomas are usually benign and can be surgically excised Note:  Metastasis is most common cause of cardiac tumor  Cardiac sarcomas are rare, but when they occur malignant tumors that often metastasize 135

Marc Imhotep Cray, M.D.

Heart, rhabdomyoma, gross • This two year old child died suddenly • At autopsy, a large firm, white tumor mass found filling left ventricle • This is a cardiac rhabdomyomas • Such primary tumors of heart are rare Marc Imhotep Cray, M.D.

136

Heart, atrial myxoma, gross • Left atrium has been opened to reveal most common primary cardiac neoplasm--an atrial myxoma • These benign masses are most often attached to atrial wall, but can arise on a valve or in a ventricle • Can produce a "ball valve" effect by intermittently occluding AV valve orifice • Embolization of fragments of tumor may also occur • Myxomas are easily Dx by echocardiography Marc Imhotep Cray, M.D.

137

Heart, epicardium, metastases, gross • Primary tumors of heart are uncommon • Metastases to heart are more common, but rare overall (only about 5 to 10% of all malignancies have cardiac metastases) • Seen over surface of epicardium are pale white-tan nodules of metastatic tumor • Metastases may lead to a hemorrhagic pericarditis

Marc Imhotep Cray, M.D.

138

Congenital Heart Disease

Marc Imhotep Cray, M.D.

139

Congenital Heart Disease Type of Defect Mechanism Capsule: Cyanosis (early; less common) Tetralogy of Fallot, transposition of great vessels, truncus arteriosus, total anomalous pulmonary venous return, tricuspid atresia Late cyanotic shunt (uncorrected left to right becomes right to left) Eisenmenger syndrome (caused by ASD, VSD, PDA; results in pulmonary hypertension/polycythemia) Frequency: VSD > ASD > PDA Right-to-Left shunts: Early cyanosis Left-to-Right shunts: “Later” cyanosis Marc Imhotep Cray, M.D.

140

Type of Defect Mechanism (Acyanotic) • Ventricular Septal Defect (VSD) There is a hole within membranous or muscular portions of intraventricular septum that produces a leftto-right shunt, more severe with larger defects • Atrial Septal Defect (ASD) A hole from a septum secundum or septum primum defect in interatrial septum produces a modest leftto-right shunt • Patent Ductus Arteriosus (PDA) Ductus arteriosus, which normally closes soon after birth, remains open, and a left-to-right shunt develops

Acyanotic heart defects without shunting include: • Pulmonary stenosis (a narrowing of pulmonary valve) • Aortic stenosis • Coarctation of the aorta Marc Imhotep Cray, M.D.

141

Type of Defect Mechanism Early cyanosis • Tetralogy of Fallot Pulmonic stenosis results in right ventricular hypertrophy and a right-to-left shunt across a VSD, which also has an overriding aorta • Transposition of Great Vessels Aorta arises from right ventricle and pulmonic trunk from left ventricle; A VSD, or ASD with PDA, is needed for extrauterine survival o There is right-to-left shunting • Truncus Arteriosus There is incomplete separation of aortic and pulmonary outflows, along w VSD, which allows mixing of oxygenated and deoxygenated bld o There is right-to-left shunting

“Blue Babies” Often diagnosed prenatally or become evident immediately after birth. Usually require urgent surgical treatment and/or maintenance of a PDA Marc Imhotep Cray, M.D.

142

Heart, tetralogy of Fallot, diagram  Diagram depicts features of Tetralogy of Fallot:  Ventricular septal defect;  Overriding aorta;  Pulmonic stenosis;  Right ventricular hypertrophy  Obstruction to right ventricular outflow creates a right-to-left shunt that leads to cyanosis

Marc Imhotep Cray, M.D.

143

Heart, transposition of great vessels, diagram  In diagram, transposition of great vessels is shown occurs when trunco-conal septum does not spiral down Instead, it descends straight down As a result outflow of right ventricle is into aorta and outflow from left ventricle is into pulmonic trunk  In order for this system to work, there must be a connection betw. system and pulmonic circulations Sometimes this is through a VSD or an ASD In diagram, this is through a patent ductus arteriosus Marc Imhotep Cray, M.D.

144

Type of Defect Mechanism • Hypoplastic Left Heart Syndrome There are varying degrees of hypoplasia or atresia of aortic and mitral valves, along with a small to absent left ventricular chamber • Coarctation of Aorta Either just proximal (infantile form) or just distal (adult form) to ductus is a narrowing of aortic lumen leading to outflow obstruction • Total Anomalous Pulmonary Venous Return (TAPVR) pulmonary veins do not directly connect to left atrium drain into left innominate vein, coronary sinus, or some other site leading to possible mixing of blood and right-sided overload Marc Imhotep Cray, M.D.

145

Heart, atrial septal defect, gross • In region of foramen ovale on inter-atrial septum is a small atrial septal defect, as seen in this heart opened on t right side • Here defect is not closed by septum secundum, so a shunt exists across from left to right

Marc Imhotep Cray, M.D.

146

Heart, ventricular septal defect, gross • This is heart of a premature stillborn w Trisomy 13 in which a ventricular septal defect is visible in membranous septum • About 90% of VSD's are in membranous septum and 10% in muscular septum

Marc Imhotep Cray, M.D.

147

Aorta, coarctation, gross • This portion of aorta was resected from a patient with a coarctation • The aorta narrows postductally here to about a 3 mm opening

Marc Imhotep Cray, M.D.

148

Aorta, coarctation, gross • Aorta is opened longitudinally here to reveal a coarctation • In region of narrowing, there was increased turbulence that led to increased atherosclerosis

Marc Imhotep Cray, M.D.

149

Congenital cardiac defect associations Disorder

Defect

Alcohol exposure in utero (fetal alcohol syndrome)

VSD, PDA, ASD, tetralogy of Fallot

Congenital rubella

PDA, pulmonary artery stenosis, septal defects

Down syndrome

AV septal defect (endocardial cushion defect), VSD, ASD

Infant of diabetic mother

Transposition of great vessels, VSD

Marfan syndrome

MVP, thoracic aortic aneurysm and dissection, aortic regurgitation

Prenatal lithium exposure

Ebstein anomaly

Turner syndrome

Bicuspid aortic valve, coarctation of aorta

Williams syndrome

Supravalvular aortic stenosis

22q11 syndromes

Truncus arteriosus, tetralogy of Fallot

USMLE Step 1 First Aid, 2020, Pg. 300.

Marc Imhotep Cray, M.D.

150

Cardiomyopathies

Marc Imhotep Cray, M.D.

151

Clinical Vignette10 A 20-year-old college football player suddenly collapses and dies during a practice session. His father had suffered a similar fate in his early 30s. On autopsy, he is found to have a hypertrophied heart with an enlarged intraventricular septum.

On histologic examination of the myocardium, you see disoriented, tangled, hypertrophied myocardial fibers and you suspect that his death was related to an autosomal dominant condition resulting in a mutation of beta-myosin heavy chain protein gene.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

152

Cardiomyopathy Etiology:  Dilated: Most common cardiomyopathy (90%); causes include alcoholism, chronic ischemia, wet beriberi (vitamin B1 deficiency), postmyocarditis, cocaine abuse, doxorubicin toxicity, peripartum cardiomyopathy, and muscular dystrophies

 Hypertrophic: Idiopathic or resulting from autosomal dominant mutation in β-myosin heavy chain gene  Restrictive: Can be idiopathic or caused by radiation, sarcoidosis, amyloidosis, Hemochromatosis, Löffler endomyocardial fibrosis, systemic sclerosis, radiation and endocardial fibroelastosis Marc Imhotep Cray, M.D.

153

Cardiomyopathy (2) Pathology and Pathophysiology:  Dilated: Dilation of all chambers; hypertrophy of muscle cells; interstitial fibrosis; results in systolic dysfunction  Hypertrophic: Hypertrophy of interventricular septum and myocardium; banana-shaped LV lumen; haphazard arrangement of hypertrophied myocytes; results in LV outflow tract obstruction and impaired diastolic filling leading to decreased CO  Restrictive: Bi-atrial dilation; diffuse interstitial fibrosis; results in decreased ventricular compliance with decreased diastolic filling and decreased CO Marc Imhotep Cray, M.D.

154

Cardiomyopathy (3) Clinical Manifestations:  Dilated: Signs of CHF Imaging: CXR demonstrates balloon heart  Hypertrophic: Dyspnea; angina; syncope w exertion; palpitations; sudden death  Restrictive: Dyspnea; exercise intolerance; weakness; edema Treatment:  Dilated: ACEIs; anticoagulants; diuretics; transplant  Hypertrophic: β-blockers; refrain from strenuous exercise  Restrictive: Treatment of underlying cause

Marc Imhotep Cray, M.D.

155

Capsule of CMP Findings • Dilated (Congestive)= Most common cardiomyopathy (90% of cases) All four chambers are dilated, and there is also hypertrophy o Most common cause is chronic alcoholism, though some may be the end-stage of remote viral myocarditis

• Hypertrophic = most common form is idiopathic hypertrophic subaortic stenosis (IHSS) results from asymmetric interventricular septal hypertrophy resulting in left ventricular outflow obstruction • Restrictive Myocardium is infiltrated with a material that results in impaired ventricular filling • Most common causes are postradiation fibrosis, amyloidosis and hemochromatosis Marc Imhotep Cray, M.D.

156

Heart, dilated cardiomyopathy, gross • This very large heart has a globoid shape b/c all of the chambers are dilated • It felt very flabby, and myocardium was poorly contractile • This is an example of a cardiomyopathy • This term is used to denote conditions in which myocardium functions poorly and heart is large and dilated, but there is no specific histologic finding Marc Imhotep Cray, M.D.

157

Heart, dilated cardiomyopathy, [XRAY] • This chest radiograph demontrates marked cardiomegaly, with t left heart edge appearing far to left

Marc Imhotep Cray, M.D.

158

Heart, cardiomyopathy, micro.

• Microscopically, heart demonstrates hypertrophy of myocardial fibers (which also have prominent dark nuclei) along w interstitial fibrosis

Marc Imhotep Cray, M.D.

159

Heart, hypertrophic cardiomyopathy, explanted heart, gross • There is marked left ventricular hypertrophy, w asymmetric bulging of a very large interventricular septum into left ventricular chamber • About half of these cases are familial, though a variety of different genes may be responsible for this disease • Both children and adults can be affected, and sudden death can occur • Seen here is explanted heart Pacemaker wires enter right Marc Imhotep Cray, M.D. ventricle

160

Dilated cardiomyopathy

Hypertrophic Obstructive cardiomyopathy

USMLE Step 1 First Aid, 2020, Pg. 309.

 Dilated cardiomyopathy will result in systolic dysfunction b/c heart becomes so massively enlarged that it cannot pump adequately In contrast,  Hypertrophic cardiomyopathy will result in diastolic dysfunction because there is so much extra myocardium that the chambers cannot fill with an adequate quantity of blood Marc Imhotep Cray, M.D.

161

Arterial and Venous Diseases

Marc Imhotep Cray, M.D.

162

Clinical Vignette 11 A 45-year-old obese white man presents to the clinic for an annual checkup. He has no complaints other than occasional headaches. During the history, you find that he is a smoker and has a family history of heart disease. His physical examination is significant for mild obesity and a blood pressure of 160/100.

You suggest lifestyle changes including weight loss, a low-salt diet, and smoking cessation, and you also prescribe hydrochlorothiazide to treat his condition.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

163

Essential and Secondary Hypertension Etiology and Epidemiology:  Primary (idiopathic) (90%): Risk factors include old age, race, diabetes, smoking, obesity, and positive family history  Secondary (10%): Caused by renal parenchymal disease, renovascular disease, Conn syndrome, Cushing syndrome, pheochromocytoma, Obstructive sleep apnea (OSA), and drug reactions (OCP, NSAIDS, steroids) Pathology and Pathophysiology:  Microscopic: Hyaline thickening of vessels; atherosclerosis  Pathophysiology: Primary (essential) HTN has been associated with increased cardiac output and increased total peripheral resistance Marc Imhotep Cray, M.D.

164

Hypertension (2)  Clinical Manifestations: Usually asymptomatic; can be associated with occasional headaches or palpitations Complications include  CAD  MI  CVA  CHF  Peripheral vascular disease  Aortic dissection  Retinopathy  Renal failure

Marc Imhotep Cray, M.D.

165

Hypertension (3) Treatment:  Reduce blood pressure to < 140/90 mm Hg with lifestyle changes and antihypertensive therapy; treat underlying causes of secondary hypertension  Lifestyle changes: Weight loss, exercise, reduce salt intake, smoking cessation, and moderate alcohol intake  Pharmacologic agents: ACE inhibitors, calcium antagonists, β-blockers, thiazide diuretics, α-blockers Note: Hypertensive renal disease can present with nephritic syndrome and is assoc. w overstimulation of RAAS

Marc Imhotep Cray, M.D.

166

Heart, hypertension with left ventricular hypertrophy, gross • This left ventricle is very thickened (slightly over 2 cm in thickness), but the rest of the heart is not greatly enlarged • This is typical for hypertensive heart disease • The hypertension creates a greater pressure load on the heart to induce the hypertrophy

Marc Imhotep Cray, M.D.

167

Heart, concentric hypertrophy with hypertension, gross • Left ventricle is markedly thickened in this patient w severe hypertension that was untreated for many years • Myocardial fibers have undergone hypertrophy

Marc Imhotep Cray, M.D.

168

Concentric hypertrophy is assoc. w increased left ventricular wall thickness whereas Eccentric hypertrophy is characterized by dilatation of left ventricular chamber; 169 however increase in overall size of cardiomyocytes under both conditions Marc Imhotep Cray, M.D.

Eccentric vs Concentric Hypertrophy Key Points (1)  

Dilated cardiomyopathy Leads to systolic HF Dilated cardiomyopathy displays eccentric hypertrophy (sarcomeres added in series)



Systolic HF reduced EF (nml 55% to 70%); Incr.

EDV or volume overload ; decr. Contractility often 2° to ischemia/MI or dilated cardiomyopathy

• Ejection Fraction (EF) is an index of ventricular contractility (decr. in systolic HF; usually normal in diastolic HF)

Marc Imhotep Cray, M.D.

170

Eccentric vs Concentric Hypertrophy Key Points (2) Hypertrophic Obstructive Cardiomyopathy Leads to Diastolic HF*  Marked by ventricular concentric hypertrophy (sarcomeres added in parallel) often septal predominance (see slide 159)  Myofibrillar disarray and fibrosis  Physiology of HOCM—asymmetric septal hypertrophy and systolic anterior motion of mitral valve outflow tract obstruction Sx dyspnea, possible syncope  Other causes of concentric LV hypertrophy: Chronic Hypertension, Friedreich ataxia *Diastolic dysfunction—preserved EF, normal EDV; decr. compliance (incr. EDP or pressure overload) often 2° to myocardial hypertrophy 171

Marc Imhotep Cray, M.D.

Eccentric vs Concentric Hypertrophy Key Points (3)  CHF due to DCM or chronic IHD is characterized by dilatation of 1 or both ventricles and contractile (systolic) dysfunction  Diastolic dysfunction occurs in hypertensive heart disease, which causes concentric ventricular hypertrophy and decreased left ventricular chamber size  Asymmetric septal hypertrophy and dynamic ventricular outflow tract obstruction are characteristics of hypertrophic cardiomyopathy

Marc Imhotep Cray, M.D.

172

Check Up Question 1. A 56-year-old man is admitted to a tertiary care center after being involved in a high-speed motor vehicle accident. He was thrown from his vehicle and suffered severe head trauma along with multiple fractures involving his ribs and extremities. Despite aggressive treatment, he dies from massive cerebral edema and brain herniation the following day.

Autopsy shows increased thickness of the left ventricular wall and decreased left ventricular cavity size. The structural changes observed in this patient’s heart are most likely associated with which of the following conditions?

A. Atrial septal defect B. Hemochromatosis C. Longstanding hypertension D. Mitral insufficiency E. Normal aging F. Recent myocardial infarction G. Wolff-Parkinson-White syndrome Marc Imhotep Cray, M.D.

173

Answer The changes in this patient's left ventricle (LV) are consistent with concentric hypertrophy due to hypertensive heart disease. Concentric hypertrophy uniformly thickens the ventricular wall with the outer dimensions of the ventricle remaining almost unchanged, resulting in a narrowed ventricular cavity size. Concentric hypertrophy results from chronic elevation of ventricular pressures during systole (pressure overload). It can be caused by longstanding hypertension and aortic stenosis, both of which increase LV afterload.

Educational objective: Concentric hypertrophy results in a uniform thickening of the ventricular wall and narrowing of the ventricular cavity with the outer dimensions of the ventricle remaining virtually unchanged. This form of hypertrophy is often seen with increased ventricular afterload (pressure overload).

Eccentric hypertrophy results in dilatation of the ventricle with an associated increase in chamber size. It is typically caused by volume overload.

Cardiac Pathology Questions and Answers_UWorld #1 Marc Imhotep Cray, M.D.

174

Clinical Vignette 12 A 30-year-old African American man presents with recent-onset headaches, blurred vision, and dyspnea. On physical examination, he appears very ill and has difficulty concentrating and answering your questions. You see cottonwool spots on a funduscopic examination, a displaced forceful heart beat, and a blood pressure reading of 190/130. You immediately place the patient on IV sodium nitroprusside treatment.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

175

Malignant Hypertension Etiology and Epidemiology: Results from an accelerated course of essential or secondary HTN  More common in young African American men Pathology Arteriole: Hyperplastic arteriosclerosis (concentric, laminated onionskin thickening of arterial walls accompanied by necrotizing arteriolitis [fibrinoid deposition in arteriole walls w necrosis and inflammation])  Can result in other pathologic conditions including o LV hypertrophy and failure and o Malignant nephrosclerosis (ruptured glomerular capillaries causing flea-bitten kidney) renal failure  ESRD o CVA Marc Imhotep Cray, M.D.

USMLE Step 1 First Aid, 2020, Pg. 301.

176

Malignant Hypertension (2) Clinical Manifestations:  Presents w headache, altered mental status, blurred vision, and dyspnea  PE shows displaced forceful cardiac apex beat, presence of S4, papilledema, retinal hemorrhages and exudates, and marked DBP inc. (> 120 mm Hg) Treatment and Prognosis: Initial lowering of BP w IV agents (Nipride, hydralazine, labetalol) followed by strict BP control w oral agents  Often can result in an early death A 59-year-old African American man presents to the ER with severe headache and blood pressure of 200/110. On physical examination, he has papilledema and fundal hemorrhages. What is the diagnosis?

Marc Imhotep Cray, M.D.

Renal arteriole, fibrinoid necrosis with malignant hypertension, microscopic • One complication of hyperplastic arteriolosclerosis with malignant hypertension is fibrinoid necrosis, as seen here in a renal arteriole

Marc Imhotep Cray, M.D.

178

Hypertensive emergency (Malignant hypertension) vs Hypertensive urgency  Hypertensive emergency-also known as malignant hypertension symptoms of end-organ involvement (blurred vision, headache, retinal hemorrhages, exudates, and papilledema) as well as a significantly elevated blood pressure • Hypertensive emergency is primarily used as a specific term for a “hypertensive crisis” w a DBP≥ 120 mmHg or SBP ≥ 180 mmHg • A patient w malignant hypertension (hypertensive emergency) always has retinal papilledema as well as flame-shaped hemorrhages and exudates on ophthalmic exam  Hypertensive urgency is primarily used as a specific term of a less serious and less urgent condition (no evidence of acute end organ damage) • Term hypertensive crisis is most often used in this sense (so called severe asymptomatic hypertension) Marc Imhotep Cray, M.D.

179

Muscular artery, polyarteritis nodosa, micro.

• This muscular artery seen above and below shows a more severe vasculitis with acute and chronic inflammatory cell infiltrates, along with necrosis of vascular wall •

This is classic polyarteritis nodosa (PAN), a form of vasculitis involving mainly small to medium-sized arteries anywhere in body, but more often renal and mesenteric arteries

Marc Imhotep Cray, M.D.

180

Hyaline arteriolosclerosis, high power micro.  There are two other forms of arteriosclerosis (hardening of arteries) in addition to atherosclerosis: 1) arteriolosclerosis and 2) medial calcific sclerosis (Monckeberg's)  Arteriolosclerosis is typically seen in kidneys one form--called hyaline arteriolosclerosis-- markedly thickened arteriole to lower right this glomerulus with PAS stain  Hyaline arteriolosclerosis is seen in elderly, but more advanced lesions are seen in persons with DM and/or w HTN

Marc Imhotep Cray, M.D.

181

Monckeberg's medial calcific sclerosis Medial calcific sclerosis is a type of arteriosclerosis that typically has no significant clinical impact • Seen in this artery to right of thyroid tissue • Occurs most often in elderly • Does not have serious pathologic consequences b/c arterial lumen is not compromised • Small muscular arteries in pelvis, neck, & breast regions affected • Can also be seen involving extremities in assoc. w autonomic neuropathy in DM Marc Imhotep Cray, M.D.

182

Thrombus in small artery with thrombotic thrombocytopenic purpura (TTP), micro.

• This fibrin and platelet thrombus in a small peripheral artery in heart is characteristic for thrombotic thrombocytopenic purpura (TTP) • For this reason, pts w TTP may die from heart failure

Marc Imhotep Cray, M.D.

183

Temporal artery, giant cell arteritis, low power microscopic • Temporal arteritis  one manifestation of giant cell arteritis, which can affect mainly branches of external carotid artery, but sometimes also great vessels at aortic arch and coronaries • There is granulomatous inflammation of media • Shown here is extensive inflammation in temporal arterial wall leading to a markedly narrowed lumen Marc Imhotep Cray, M.D.

184

Temporal artery, giant cell arteritis, HP micro.

• Giant cell (temporal) arteritis occurs after age 50 • Erythrocyte sedimentation rate (ESR) is often markedly elevated (100 mm/hr or more) • C-reactive protein (CRP) is elevated, driven by incr. in interleukin-6 (IL-6) • 50% develop polymyalgia rheumatica • focal granulomatous inflammation with narrowed arterial lumen is seen here at high magnification Marc Imhotep Cray, M.D.

185

Temporal artery, giant cell arteritis, gross • Patients with giant cell arteritis may have a visible firm, palpable, painful temporal artery that courses over surface of the scalp

Marc Imhotep Cray, M.D.

186

Varicose veins, gross  Prominent veins shown here on lower leg are varicosities  Varicose veins are a common problem with aging venous valves become incompetent  There may be muscular atrophy with less tone to provide a massage effect on large superficial veins, and skin becomes less elastic with time  Hydrostatic pressure from standing for long periods exacerbates problem Marc Imhotep Cray, M.D.

187

Comparison of healthy and varicose veins

Marc Imhotep Cray, M.D.

188

Comparison of healthy and varicose veins (2)

Marc Imhotep Cray, M.D.

189

Varicose veins  Risk factors: Obesity, not enough exercise; Other related factors are pregnancy, menopause, aging  Symptoms: None, fullness or pain in area  Complications: Bleeding, superficial thrombophlebitis  Treatment: Compression stockings, exercise, surgery

Marc Imhotep Cray, M.D.

190

Congestive Heart Failure

Marc Imhotep Cray, M.D.

191

Clinical Vignette 13 A 55-year-old woman presents to your clinic complaining of ankle swelling and increasing shortness of breath with exertion. Upon directed questioning, she reveals that she also experiences shortness of breath when she is lying down.

Physical examination reveals marked hepatosplenomegaly, distended neck veins, and pedal edema. A chest x-ray is suggestive of cardiomegaly. You start the patient on an ACE inhibitor, diuretic, and a low-sodium diet and you refer her to a cardiologist.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

192

Congestive Heart Failure Etiology  Left-sided (LS): Ischemic heart disease (especially MI); hypertension; aortic/mitral valve disease; cardiomyopathies; myocarditis  Right-sided (RS): Left-sided heart failure; mitral stenosis; cor pulmonale; cardiomyopathies; myocarditis; tricuspid/pulmonary valve disease

Marc Imhotep Cray, M.D.

193

Congestive Heart Failure (2) Pathology and Pathophysiology:  LS: Hypertrophied and dilated LV; dilated LA; pulmonary congestion w hemosiderin-laden macrophages or “heart failure” cells  RS: Hypertrophied and dilated RV; usually hypertrophied and dilated LV; hepatic congestion (nutmeg liver) w centrilobular necrosis; congested spleen  Pathophysiology for both left- and right-sided failure: o LV failure leads to decreased cardiac output, resulting in dyspnea; Pulmonary edema results from LV failure to keep up w RV output, leading to increased fluid transudation from pulmonary vessels o RV failure leads to increased central venous pressure, causing hepatomegaly and peripheral edema

Marc Imhotep Cray, M.D.

194

Common causes of nonvalvular heart failure Etiology

Ischemic heart disease Dilated cardiomyopathy Hypertensive heart disease

Ventricular wall thickness Normal or decreased Increased globally

Ventricular cavity size

Contractile function

Diastolic function

Increased

Decreased

Normal

Decreased

Normal

Decreased

Hypertrophic Increased cardiomyopathy septal thickening Redrawn after USMLE World 2016, Cardiology (Pathology), Question # 14.

See: Dumitru, I. Etiology of Heart Failure. Medscape, May, 2018.

Accessed April, 2020. Available at https://emedicine.medscape.com/article/163062-overview#a4

Marc Imhotep Cray, M.D.

195

See :Congestive heart failure (CHF) - systolic, diastolic, left side, right side, & symptoms_Osmosis Marc Imhotep Cray, M.D.

196

Congestive Heart Failure (3) Clinical Manifestations:  LS: Dyspnea; orthopnea; paroxysmal nocturnal dyspnea (PND); pleural effusion; cerebral anoxia; salt and water retention  RS: Fluid retention and peripheral edema; hepatosplenomegaly; ascites; distention of neck veins Treatment: Diuretics; low-sodium diet; ACE inhibitors; nitrates; beta-blockers; digoxin Note: Cor pulmonale refers to isolated right-sided heart failure caused by chronic pulmonary hypertension Marc Imhotep Cray, M.D.

197

A man with CHF and marked jugular venous distension.

External jugular vein marked by an arrow

https://www.wikiwand.com/en/Jugular_venous_pressure Marc Imhotep Cray, M.D.

198

Severe peripheral (pitting) edema

Marc Imhotep Cray, M.D.

https://www.wikiwand.com/en/Edema

199

CHF CXR Findings

https://www.wikiwand.com/en/Heart_failure Marc Imhotep Cray, M.D.

200

Siderophages = hemosiderin-laden macrophages

https://www.wikiwand.com/en/Heart_failure Marc Imhotep Cray, M.D.

201

Companion Video Learning Series: Heart Failure_Lecturio

Model of a normal heart, with contracted muscle (left); and a weakened heart, with over-stretched muscle (right) https://www.wikiwand.com/en/Heart_failure 202

Marc Imhotep Cray, M.D.

THE END

See next side for sources and further study.

Marc Imhotep Cray, M.D.

203

Sources:  

Baron SJ; Lee, CI. Lange Pathology Flash Cards, 2nd Ed. New York, NY: Mc GrawHill, 2009.

Buja, LM; Krueger GR. Netter’s Illustrated Human Pathology 2nd Ed. Illustrations

by Frank H. Netter, MD. Philadelphia, PA: Saunders- Elsevier, 2014.



Kumar V; Abbas AK; Aster JC. Robbins Basic Pathology, 10th ed. Philadelphia:



Elsevier, 2018.

Le, T; Bhushan, V. First AID for the USMLE Step 1 2020. Mc Graw-Hill, 2020.



WebPath Online: Cardiovascular Pathology Image Plates

Further Study:  Cardiovascular Pathology Rapid Review Notes  Cardiac Pathology Questions and Answers_UWorld  Cardiovascular Pathophysiology High Yield Cases_w Questions;

Answers-Discussion  Video Edu: Cardiovascular Pathology & Pathophysiology_Osmosis

Marc Imhotep Cray, M.D.