Pbl Exam 11 Case 3

Front 1

1. What is the normal weight of the heart?

Back 1

It averages approx 250-300 g in females and 300-350 g in males.

Front 2

2. What are the five major components of the cardiac myocytes?

Back 2

1. Cell membrane (sarcolemma) and T-tubules, for impulse conduction
2. Sarcoplasmic reticulum, a calcium reservoir needed for contraction
3. Contractile elements
4. Mitochondria
5. Nucleus

Front 3

3. What does a sarcomere consist of?

Back 3

Sarcomeres are an orderly arrangement of thick filaments composed principally of myosin and thin filaments containing actin.

They also contain the regulatory proteins troponin and tropomyosin.

Front 4

4. Myocytes comprise what percentage of the cells in the heart?

Back 4

Approx 25%.

However, b/c cardiac myocytes are so much larger than the intervening cells, they account for more than 90% of the volume of the myocardium.

Front 5

5. How do atrial myocytes differ from ventricular myocytes?

Back 5

Atrial myocytes are smaller in diameter and less structured. Some atrial cells also differ in having distinctive electron dense granules in the cytoplasm called specific atrial granules. They are the sites of storage of atrial natriuretic peptide (ANP).

Front 6

6. What is ANP?

Back 6

ANP is a polypeptide secreted into the blood under conditions of atrial distention.

ANP can produce a variety of physiologic effects, including vasodilation, natriuresis, and diuresis, actions beneficial in pathologic states such as hypertension and congestive heart failure.

Front 7

7. What are intercalated disks?

Back 7

These unique cardiac muscle cells join individual cells and within specialized intercellular junctions permit both mechanical and electrical (ionic) coupling.

They have gap junctions, which facilitate synchronous myocyte contraction.

Front 8

8. What are the four specialized conduction components of the heart?

Back 8

1. SA node
2. AV node
3. Bundle of His
4. Right and left bundle branches

Front 9

9. What are the three major coronary arteries?

Back 9

1. LAD
2. LCX
3. RCA

Front 10

10. What does the LAD supply?

Back 10

LAD supplies:

1. Most of the apex of the heart
2. The anterior wall of the left ventricle
3. The anterior 2/3's of the ventricular septum

Front 11

11. What does the RCA supply?

Back 11

In right dominant circulation, it perfuses:

1. Entire right ventricular free wall
2. Posterior wall of the left ventricle
3. Posterior 1/3rd of the ventricular septum

Front 12

12. What does the LCX supply?

Back 12

In right dominant circulation, it generally perfuses only the lateral wall of the left ventricle.

Front 13

13. What is the nodule of Arantius?

Back 13

Each aortic cusp has a small nodule (nodule of Arantius) in the center of the free edge, which facilitates closure.

Front 14

14. What are the effects of aging on the heart?

Another ridiculously long list...

Back 14

1. Chambers
a. increased left atrial size
b. decreased left ventricle size
c. sigmoid-shaped ventricular septum

2. Valves
a. aortic and mitral valve calcific deposits
b. fibrous thickening of leaflets
c. Lambl excrescences

3. Coronary arteries
a. tortuosity
b. increased cross-sectional luminal area
c. calcific deposits
d. atherosclerotic plaque

4. Myocardium
a. increased mass
b. increased subepicardial fat
c. Brown atrophy
d. lipofuscin deposition
e. basophilic degeneration
f. amyloid deposits

5. Aorta
a. dilated ascending aorta w/rightward shift
b. elongated and tortuous thoracic aorta
c. elastic fragmentation and collagen accumulation
d. atherosclerotic plaque

Front 15

15. What are the 5 principal mechanisms by which cardiovascular dysfunctions occur?

Back 15

1. Failure of the pump
2. Blood flow obstruction
3. Regurgitant flow
4. Disorders of cardiac conduction
5. Disruption of the continuity of the circulatory system, or shunts

Front 16

16. What is the contemporary view of the cause of cardiovascular diseases?

Back 16

Most clinical cardiovascular diseases result form a complex interplay of genetics and environmental factors that disrupt networks controlling morphogenesis, myocyte survival, biomechanical stress responses, contractility, and electrical conduction.

Front 17

17. What is CHF?

Back 17

Congestive heart failure is the common end point of many forms of heart disease.

It is a pathologic state in which impaired cardiac function renders the heart unable to maintain output sufficient for the metabolic requirements of the body.

CHF is characterized by diminished cardiac output, accumulation of blood in the venous system, or both.

Front 18

18. What are the 3 main mechanisms by which the cardiovascular system maintains arterial pressure?

Back 18

1. Frank-Starling mechanism

2. Hypertrophy, w/ or w/o cardiac chamber dilation

3. Activation of the neurohumoral systems
-CNS
-Renin-angiotensin-aldosterone
-Atrial natriuretic peptide

Front 19

19. What causes most instances of heart failure?

Back 19

Most instances of heart failure are the consequence of progressive deterioration of myocardial contractile function (systolic dysfunction).

Front 20

20. When does diastolic dysfunction occur?

Back 20

Occasionally, failure results from inability of the heart chambers to relax sufficiently during diastole so that the ventricles can properly fill.

***This can occur with massive left ventricular hypertrophy, myocardial fibrosis, deposition of amyloid, or constrictive pericarditis.

Front 21

21. What are the three compensatory mechanisms in response to CHF?

Back 21

1. Ventricular dilation
2. Blood volume expansion by salt and water retention
3. Tachycardia

Unfortunately, these changes ultimately impose further burdens on cardiac function.

Front 22

22. What are the early mediators of hypertrophy?

Back 22

c-fos, c-myc, c-jun, and ERG1.

Selective up-regulation or re-expression of embryonic/fetal forms of contractile and other proteins also occurs.

Front 23

23. Cardiac hypertrophy summary

Back 23

The geometry, structure, and composition of the hypertrophied heart are not normal. Cardiac hypertrophy constitutes a tenuous balance between adaptive characteristics and potentially deleterious structural and biochemical/molecular alterations, (including decreased capillary-to-myocyte ratio, increased fibrous tissue, and synthesis of abnormal proteins).

***Thus, sustained cardiac hypertrophy often evolves to cardiac failure.

Front 24

24. What are the 4 most common causes of left-sided heart failure?

What causes the clinical effects of left-sided CHF?

Back 24

1. Ischemic heart disease
2. Hypertension
3. Aortic and mitral valvular disease
4. Nonischemic myocardial disease

The clinical effects of left-sided CHF primarily result from progressive damming of blood within the pulmonary circulation and the consequences of diminished peripheral blood pressure and flow.

Front 25

25. What is the morphology of the heart in left-sided heart failure?

Back 25

Depends on the disease process; abnormalities such as MI or a valvular deformity may be present. Except for obstruction @ the mitral valve or other processes that restrict the size of the left ventricle, this chamber is usually hypertrophied and often dilated, with some fibrosis.

Secondary enlargement of the left atrium w/resultant atrial fibrillation may either compromise stroke volume or cause blood stasis and possible thrombus formation (particularly in the atrial appendage).

Front 26

26. What causes a substantially increased risk of embolic stroke in left sided heart failure?

Back 26

A fibrillating left atrium carries a substantially increased risk of embolic stroke.

Front 27

27. What is the morphology of the lungs in left sided heart failure?

Back 27

Pressure in the pulmonary veins mounts and is ultimately transmitted retrograde to the capillaries and arteries. The result is pulmonary congestion and edema, w/heavy, wet lungs.

*Cough is a common accompaniment of left-sided heart failure.

Front 28

28. What are the 4 pathologic changes in the lungs due to left-sided heart failure?

Back 28

1. A perivascular and interstitial transudate, particularly in the interlobular septa, responsible for Kerley's B lines
2. Progressive edematous widening of alveolar septa
3. Accumulation of edema fluid in the alveolar spaces
4. Hemosiderin-containing macrophages in the alveoli (called siderophages or heart failure cells) denote previous episodes of pulmonary edema

Front 29

29. What are the 3 clinical effects of these pathologic changes in the lungs due to left-sided heart failure?

Back 29

1. Dyspnea is the cardinal complaint
2. Orthopnea
3. Paroxysmal nocturnal dyspnea

Front 30

30. What is the morphology of the kidneys due to left-sided heart failure?

Back 30

Reduced renal perfusion (due to diminished CO), causes salt and water retention, ischemic acute tubular necrosis, and impaired waste excretion.

***If severe enough, this can lead to prerenal azotemia.

Front 31

31. What is the morphology of the brain and CNS in left-sided heart failure?

Back 31

Reduced central nervous system perfusion, often causes hypoxic encephalopathy, with symptoms ranging from irritability, loss of attention span, restlessness, to coma.

Front 32

32. What is right-sided heart failure?

What is the most common cause of right-sided heart failure?

Back 32

Right sided heart failure is most commonly caused by left-sided failure.

Pure right-sided heart failure can be caused by tricuspid or pulmonary valvular disease, or by intrinsic pulmonary or pulmonary vasculature disease causing functional, right ventricular outflow.

Front 33

33. Pure right sided heart failure most often occurs w/what?

Back 33

Pure right sided heart failure most often occurs w/chronic severe pulmonary hypertension and thus is called "cor pulmonale".

In this condition, the right ventricle is burdened by a pressure workload due to increased resistance w/in the pulmonary circulation.

Front 34

34. How do the major morphologic and clinical effects of pure right-sided heart failure differ from that of left-sided heart failure?

Back 34

In right-sided heart failure, pulmonary congestion is minimal, whereas engorgement of the systemic and portal venous systems may be pronounced.

Front 35

35. What are the 4 major manifestations of right-sided heart failure?

Back 35

1. Portal, systemic, and dependent peripheral congestion and edema (anasarca), with effusions
2. Hepatomegaly with centrilobular congestion and atrophy of central hepatocytes, producing a nutmeg appearance.
3. Congestive splenomegaly with sinusoidal dilation, focal hemorrhages, hemosiderin deposits, and fibrosis
4. Renal congestion, hypoxic injury, and ATN (more marked in right vs. left sided CHF)

Front 36

36. Centrilobular necrosis in the liver can lead to...?

Back 36

With long standing right sided CHF, the central areas can become fibrotic, creating so-called "cardiac sclerosis" or "cardiac cirrhosis".

Front 37

37. How do the symptoms of left sided CHF differ from right sided CHF?

Back 37

The symptoms of pure left-sided HF are largely due to pulmonary congestion and edema.

In contrast, in right-sided HF, respiratory symptoms may be absent or insignificant, and there is a systemic and portal venous congestive syndrome, with hepatic and splenic enlargement, peripheral edema, pleural effusion, and ascites.

Front 38

38. In many cases of chronic cardiac decompensation, how does the patient present?

Back 38

In many cases of chronic cardiac decomp, the patient presents with the picture of biventricular CHF, encompassing the clinical syndromes of both right- and left-sided heart failure.

Front 39

39. What is congenital heart disease?

Back 39

Congenital heart disease is a general term used to describe abnormalities of the heart or great vessels that are present from birth; most are attributable to faulty embryogenesis during gestational weeks 3-8, when major cardiovascular structures develop.

The most severe anomalies may be incompatible with intrauterine survival; defects that permit embryologic maturation and birth generally involve only specific chambers or regions of the heart, while the remainder of the heart develops normally.

Front 40

40. What are the top three congenital cardiac manifestations?

Back 40

1. VSD (42%)
2. ASD (10%)
3. Pulmonary stenosis (8%)

Front 41

41. What is the role of genetic factors in congenital heart disease?

Back 41

Well defined genetic causes are only identifiable in (10%) of cases.

The obvious role of genetic factors in these cases is demonstrated by the occurrence of familial forms of congenital heart disease and by an association of congenital cardiac malformations with certain chromosomal abnormalities (e.g. trisomies 13, 15, 18, and 21, and the Turner syndrome).

A congenital heart defect in a parent or preceding sibling is the greatest risk factor for developing a cardiac malformation.

Front 42

42. What infections can lead to congenital heart disease?

Back 42

Congenital rubella infection

Front 43

43. Mutations of what genes cause the ASD and VSD observed in the Holt-Oram syndrome?

Back 43

Mutation of the gene that encodes the transcription factor, TBX5, has been shown to cause the ASD and VSD observed in the Holt-Oram syndrome, a rare hereditary condition associated with heart, arm, and hand defects.

Front 44

44. What is NKX2.5?

Back 44

The gene encoding fo rthe transcription factor NKX2.5 causes nonsyndromic (isolated) ASD in humans when one copy is missing.

This gene is the the human counterpart of the tinman gene of the fruit fly, b/c fruit fly embryos lacking both copies of tinman have no hearts.

Front 45

45. The wide range of anomalies of the outflow tract are caused by what?

Back 45

Developmental errors in mesenchymal tissue migration.

Outflow tract defects may be caused by the abnormal development of neural crest derived cells, whose migration into the embryonic heart is required for formation of the outflow tracts of the heart.

Front 46

46. What chromosome is associated with the (ab)normal development of the conotruncus, branchial arches, and the face?

Back 46

Chromosome 22q11.2 deletions are seen in 15-50% of these disorders.

These include development anomalies of the fourth branchial arch and derivatives of the third and fourth pharyngeal pouches.

Hypoplasia of the thymus and parathyroids causes immune deficiency (Di George syndrome) and hypocalcemia.

Front 47

47. What are 2 other common mechanisms of congenital heart disease?

Back 47

1. ECM abnormalities (endocardial cushion defects and AV septal defects in Down syndrome)

2. Situs and looping defects (may arise from single genes that have a major effect on determining laterality).

Front 48

48. What are the clinical features of congenital anomalies of the heart?

Back 48

They not only have direct hemodynamic sequelae, but also have cyanosis, retarded development, and failure to thrive.

They are at increased risk of chronic or recurrent illness and of infective endocarditis (due to abnormal valves or endocardial injury from jet lesions

Front 49

49. What are left-to-right shunts?

When are they not surgically correctable?

Back 49

Left-to-right shunts induce chronic right-sided volume overload with secondary pulmonary hypertension and right ventricle hypertrophy; eventually, right sided pressured exceed left sided pressures, and the shunt becomes right to left.

Hence, cyanosis appears late.

Once significant pulmonary hypertension develops, the underlying structural defects are no longer candidates for surgical correction.

Front 50

50. What are the 3 major left-to-right shunts?

Back 50

1. ASD
2. VSD
3. PDA

Front 51

51. What are ASDs?

Back 51

An ASD is an abnormal opening in the atrial septum that allows communication of blood between the left and right atria.

ASD is the most common congenital cardiac anomaly seen in adults. It is usually asymptomatic until adulthood.

Front 52

52. What are the 3 types of ASDs?

Back 52

1. Primum type: only 5% of ASDs, but common in Down syndrome, this type occurs low in the atrial septum, and occasionally is associated with mitral valve deformities

2. Secundum type: 90% of ASDs; this type occurs at the foramen ovale, may be any size, and may be single, multiple, or fenestrated. Secundum type usually is not associated w/other anomalies.

3. Situs venosus type: 5% of ASDs; this type occurs high in the septum near the SVC entrance. It can be associated w/anomalous right pulmonary vein drainage into the SVC or right atrium.

Front 53

53. What is the morphology of ASDs?

Back 53

ASDs result in a left-to-right shunt, largely b/c pulmonary vascular resistance is considerably less than systemic vascular resistance and b/c the compliance of the right ventricle is much greater than that of the left.

Pulmonary blood flow may be 2-4x normal. Although some neonates may be in profound CHF, most isolated ASDs are well tolerated and usually do not become symptomatic before age 30. A murmur is often present as a result of excessive flow through the pulmonary valve.

Eventually, volume hypertrophy of the right atrium and right ventricle develops.

Front 54

54. Why do ASDs become symptomatic after age 30?

Back 54

In adulthood, either right sided heart failure occurs or gradually increasing right-sided hypertrophy and pulmonary hypertension finally induce right-to-let shunting w/cyanosis.

Early surgical correction is advocated to prevent pulmonary vascular changes.

Front 55

55. What are VSDs?

Back 55

Incomplete closure of the ventricular septum, allowing free communication and thus a shunt from left to right ventricles.

*Frequently, VSD is associated w/other structural defects, such as tetralogy of Fallot.

Depending on the size of the defect, it may produce difficulties virtually from birth or, with smaller lesions, may not be recognized until later or may even spontaneously close.

Front 56

56. What are the classifications of the VSDs?

Back 56

Most are about the size of the aortic valve orifice. **About 90% involve the region of the membranous septum (membranous VSD).**

The remainder lie below the pulmonary valve (infundibular VSD) or within the muscular septum.

Although most often single, VSDs in the muscular septum may be multiple.

Front 57

57. With moderate-sized VSDs, patients are at increased risk of what...?

Back 57

Infective endocarditis

Front 58

58. What is the clinical course of VSDs?

Back 58

Depending on the VSD size, the clinical picture ranges from fulminant CHF to late cyanosis, to asymptomatic holosystolic murmurs, to spontaneous closure (50% of those <0.5 cm diameter).

Surgical closure of asymptomatic VSDs is generally not attempted during infancy. However, surgical correction is desirable at age 1 year with large defects before right-sided heart overload and pulmonary hypertension develop.

Front 59

59. What is a PDA?

Back 59

At birth, under the influence of higher oxygen tensions and reduced local prostaglandin E synthesis, muscular contraction normally closes the ductus within 1 or 2 days of life. Persistence patency beyond that point is generally permanent.

About 85-90% of PDA occur as isolated defects. Left ventricular hypertrophy and pulmonary artery dilation occur secondary to ductus patency.

Front 60

60. What are the consequences of PDA?

Back 60

Although initially asymptomatic (but notable for a prominent machinery-like heart murmur), long standing PDA causes pulmonary hypertension followed by right ventricle hypertrophy and eventually right to left shunting with late cyanosis.

Early PDA closure (either surgically or with prostaglandin synthesis inhibitors) is advocated.

Front 61

61. What are right-to-left shunts?

What are the primary and secondary findings in these shunts?

Back 61

Right-to-left shunts (cyanotic congenital heart disease) cause cyanosis from the outset by allowing poorly oxygenated blood to flow directly into the systemic circulation (they also permit paradoxical embolism).

Secondary findings include:
1. Fingers and toe clubbing
2. Hypertrophic osteoarthropathy
3. Polycythemia

Front 62

62. What are the 3 major congenital right-to-left shunts?

Back 62

1. Tetralogy of Fallot
2. Transposition of the great arteries
3. Truncus arteriosus

Front 63

63. What is Tetralogy of Fallot?

Back 63

Owing to anterosuperior displacement of the infundibular septum, the cardinal finding are:

1. VSD
2. Overriding aorta
3. Pulmonary stenosis w/right ventricle outflow obstruction
4. Right ventricular hypertrophy

Front 64

64. What is the clinical course of Tetralogy?

Back 64

Symptom severity is directly related to the extent of right ventricle outflow obstruction.

With a large VSD and mild pulmonary stenosis, there is minimal left-to-right shunt without cyanosis. More severe pulmonary stenosis produces a cyanotic right-to-left shunt.

With complete pulmonary obstruction, survival can occur only by flow through a PDA or dilated bronchial arteries.

Surgical correction can be delayed provided that the child can tolerate the level of oxygenation; when present, pulmonary valvular stenosis protects the lung form volume and pressure overload, and right ventricular failure is rare b/c it can pump excess volume into the left ventricle and aorta.

Front 65

65. What is the shape of the heart in Tetralogy?

Back 65

The heart is often "boot shaped" owing to marked right ventricular hypertrophy, particularly of the apical region.

Front 66

66. What is transposition of the great arteries (TGA)?

Back 66

Transposition of the great arteries means the aorta arise from the right ventricle and the pulmonary artery emanates from the left ventricle.

The AV connections are normal, with right atrium joining right ventricle and left atrium emptying into the left ventricle.

Front 67

67. What is the essential embryologic defect in complete TGA?

Back 67

Abnormal formation of the truncal and aortopulmonary septa.

The aorta arises from the right ventricle and lies anterior and to the right of the pulmonary artery.

The result is separation of the systemic and pulmonary circulations, a condition incompatible with postnatal life unless a shunt exists for adequate mixing of blood.

Front 68

68. What is the clinical course of TGA?

Back 68

1. Right-to-left-shunting causes early cyanosis
2. Eventually the flow reverses, and patients develop right ventricle hypertrophy and pulmonary hypertension. The anomaly carries a poor prognosis.

Front 69

69. What type of shunts can permit survival in TGA?

Back 69

Patients with TGA and a VSD (about 35%) have a stable shunt.

Those with only a patent foramen ovale or PDA (about 65%), however, have unstable shunts that tend to close and therefore require immediate intervention to create a shunt.

Front 70

70. What is a persistent truncus arteriosus?

Back 70

The persistent truncus arteriosus arises from a developmental failure of separation of the embryologic truncus arterious into the aorta and pulmonary artery. This results in a single great artery that receives blood from both ventricles, accompanied by an underlying VSD, and this gives rise to the systemic, pulmonary, and coronary circulations.

B/c blood from the right and left ventricle mixes, there is early systemic cyanosis as well as increased pulmonary blood flow, with the danger of irreversible pulmonary hypertension.

Front 71

71. What is tricuspid atresia?

Back 71

Complete occlusion of the tricuspid valve orifice is known as tricuspid atresia.

It results embryologically from unequal division of the AV canal, and thus the mitral valve is bigger than normal.

This lesion is almost always associated w/underdevelopment of the right ventricle.

The circulation is maintained by a right-to-left shunt through an interatrial communication (ASD or patent foramen ovale).

A VSD is also present and affords communication between the left ventricle and the great artery that arises form the hypoplastic right ventricle. Cyanosis is present virtually from birth, and there is a high mortality in the first weeks or months of life.

Front 72

72. What is a total anomalous pulmonary venous connection (TAPVC)?

Back 72

TAPVC, in which no pulmonary veins directly join the left atrium, results embryologically when the common pulmonary vein fails to develop or becomes atretic, causing primitive systemic venous channels from the lungs to remain patent.

TAPVC usually drains into the left innominate vein or to the coronary sinus.

Either a patent foramen ovale or an ASD is always present, allowing pulmonary venous blood to enter the left atrium.

Front 73

73. What are the consequences of TAPVC?

Back 73

The consequences of TAPVC include volume and pressure hypertrophy of the right atrium and right ventricle, and these chambers and the pulmonary trunk are dilated.

The left atrium is hypoplastic, but the left ventricle is usually normal in size.

Cyanosis may be present, owing to mixing of well-oxygenated and poorly oxygenated blood at the site of anomalous pulmonary venous connection and a large right-to-left shunt at the ASD.

Front 74

74. What are the 2 classic forms of coarctation of the aorta?

Back 74

1. An infantile form with tubular hypoplasia of the aortic arch proximal to a PDA that is often symptomatic in early childhood

2. And adult form in which there is a discrete ridge-like infolding of the aorta, just opposite the closed ductus arteriosus distal to the arch vessels.

Front 75

75. What are some common defects that accompany coarctation of the aorta?

Back 75

Although coarctation may arise as a solitary defect, it is accompanied by a bicuspid aortic valve in 50% of cases and may also be associated w/congenital aortic stenosis, ASD, VSD, mitral regurgitation, and berry aneurysms of the circle of Willis.

Front 76

76. What are the signs and symptoms of coarctation with a PDA?

Back 76

Usually leads to manifestations early in life; indeed, it may cause signs and symptoms immediately after birth. Many infants w/this anomaly do not survive the neonatal period without surgical or catheter-based intervention.

In such cases, the delivery of unsaturated blood through the ductus arteriosus produces cyanosis localized to the lower half of the body.

Front 77

77. What are the signs and symptoms of coarctation without a PDA?

Back 77

Most of the children are asymptomatic, and the disease may go unrecognized until well into adult life.

Typically there is hypertension in the upper extremities, but there are weak pulses and a lower blood pressure in the lower extremities, associated w/manifestations of arterial insufficiency (i.e. claudication and coldness).

Particularly characteristic in adults is the development of collateral circulation between the precoarctation arterial branches and the postcoarctation arteries through enlarged intercostal and internal mammary arteries and the "rib notching".

Front 78

78. What are some common symptoms in all coarctations?

How is it treated surgically?

Back 78

With all significant coarctations, murmurs are often present throughout systole.

Sometimes a thrill may be present,and there is cardiomegaly owing to left ventricular hypertrophy.

With uncomplicated coarctation of the aorta, surgical resection and end-to-end anastomosis or replacement of the affected aortic segment by a prosthetic graft yields excellent results.

Front 79

79. What is pulmonary stenosis and atresia?

Back 79

This relatively frequent malformation constitutes an obstruction at the pulmonary valve, which may be mild to severe.

It may occur as an isolated defect, or as part of a more complex anomaly - either tetralogy of Fallot or TGA.

Right ventricular hypertrophy often develops and there is sometimes poststenotic dilation of the pulmonary artery owing to jetstream injury to the wall.

When the valve is entirely atretic, there is no communication between the right ventricle and lungs, and so the anomaly is commonly associated with a hypoplastic right ventricle and an ASD; flow enters the lungs through a PDA.

Front 80

80. What is the clinical course of pulmonary stenosis?

Back 80

Mild stenosis may be asymptomatic and compatible with long life. The smaller the valvular orifice, the more severe is the cyanosis and the earlier its appearance.

Front 81

81. What are the 3 types of aortic stenoses?

Back 81

1. Valvular aortic stenosis
2. Subaortic stenosis
3. Supravalvular aortic stenosis

Front 82

82. What is valvular aortic stenosis?

Back 82

In valvular aortic stenosis, the cusps may be hypoplastic, dysplastic (thickened, nodular), or abnormal in number.

In severe aortic stenosis or atresia, obstruction of the left ventricular outflow tract leads to underdevelopment of the left ventricle and ascending aorta.

There may be dense porcelain-like left ventricular endocardial fibroelastosis.

The ductus may be open to allow blood flow to the aorta and coronary arteries. This constellation of findings, called the hypoplastic left heart syndrome, is nearly always fatal in the first week of life, when the ductus closes.

Front 83

83. What is subaortic stenosis?

Back 83

Subaortic stenosis represent either a thickened ring or collar of dense endocardial fibrous tissue below the level of the cusps.

Front 84

84. What is supravalvular aortic stenosis?

Back 84

Supravalvular aortic stenosis represents an inherited form of aortic dysplasia in which the ascending aortic wall is greatly thickened, causing luminal constriction.

**It may be related to a development disorder affecting multiple organ systems, including the vascular system, which includes hypercalcemia of infancy (Williams syndrome)**.

Front 85

85. Mutations in which gene are responsible for supravalvular aortic stenosis?

Back 85

Mutations in the elastin gene cause supravalvular aortic stenosis, probably via disruption of an important elastin-smooth muscle cell interactions in arterial morphogenesis.

Front 86

86. What are the clinical features of aortic stenosis?

Back 86

A prominent systolic murmur is usually detectable and sometimes a thrill, which does not distinguish the site of stenosis.

Pressure hypertrophy of the left ventricle develops as a consequence of the obstruction to blood flow.

In general, congenital stenoses are well tolerated unless very severe. Mild stenoses can be managed conservatively with antibiotic prophylaxis and avoidance of strenuous activity, but the threat of sudden death with exertion always looms.

Front 87

87. Ischemic heart disease (IHD)

The clinical manifestations of IHD can be divided into what 4 syndromes?

Back 87

Group of closely related syndromes resulting from myocardial ischemia; an imbalance between the supply (perfusion) and demand of the heart for oxygenated blood.

Can be divided into four syndromes:
1. Myocardial infarction
2. Angina pectoris
3. Chronic IHD w/heart failure
4. Sudden cardiac death

Front 88

88. What is the cause of myocardial ischemia in more than 90% of cases?

Back 88

Reduction in coronary blood flow due to atherosclerotic coronary arterial obstruction.

In most cases, there is a long period of silent, slowly progressive coronary atherosclerosis before these disorders become manifest.

Thus, IHD is often termed CAD or coronary heart disease

Front 89

89. What 3 conditions aggravate ischemia?

Back 89

1. Increases in cardiac energy demand (hypertrophy)

2. Diminished availability of blood or O2 due to lowered systemic blood pressure (shock or hypoxemia)

3. Increased heart rate which decreases coronary blood supply

Front 90

90. The risk of developing detectable IHD depends on what?

Back 90

Regarding atheromatous plaques:
1. Number
2. Distribution
3. Structure
4. Degree of narrowing they cause

Front 91

91. Epidemiology of IHD

Back 91

Leading cause of death for both males and females int he US and other industrialized nations

Nearly 500,000 Americans dies of IHD each year

However, the death rate has fallen in the US by approx 50% since 1963

Front 92

92. Why the 50% fall in IHD death rate since 1963?

Back 92

1. Prevention achieved by modification of determinants of risk, such as smoking, elevated blood cholesterol, hypertension, and a sedentary lifestyle

2. Diagnostic and therapeutic advances, allowing earlier, more effective, and safer treatments.

Front 93

93. Pathogenesis of IHD

Back 93

The dominant influence in the causation of the IHD syndromes is diminished coronary perfusion relative to myocardial demand, owing largely to a complex and dynamic interaction among fixed atherosclerotic narrowing of the epicardial coronary arteries, intraluminal thrombosis overlying a disrupted atherosclerotic plaque, platelet aggregation, and vasospasm.

Front 94

94. Causes of coronary atherosclerosis

What degrees of stenosis are associated w/clinical symptoms?

Back 94

Clinical manifestations are generally due to progressive encroachment of the lumen leading to stenosis or to acute plaque disruption w/thrombosis which compromises blood flow.

Obstructive lesion of 75% or greater generally causes symptomatic ischemia induced by exercise

90% stenosis can lead to inadequate coronary blood flow, even at rest.

Front 95

95. Common locations of stenosing plaques

Back 95

Can happen anywhere but tend to predominate within:

1. First several cm of the LAD and LCX
2. Along entire length of RCA

Front 96

96. What is the role of acute plaque change?

Back 96

In most patients, myocardial ischemia underlying unstable angina, acute MI, and sudden cardiac death is precipitated by abrupt plaque change followed by thrombosis.

Often, the initiating event is disruption of a previously only partially stenosing plaque w/any of the following:
1. Rupture/fissuring
2. Erosion/ulceration
3. Hemorrhage into the atheroma

Front 97

97. What are vulnerable plaques?

Back 97

Plaques that contain large areas of foam cells and extracellular lipids and those in which the fibrous caps are thin or contain few smooth muscle cells or have clusters of inflammatory cells.

These plaques are most likely to rupture.

Front 98

98. What determines the strength of the fibrous caps?

Back 98

The fibrous cap undergoes continuous remodeling; balance of synthetic and degradative activity of collagen, the major structural component of the fibrous cap accounts for its mechanical strength and determines plaque stability and prognosis

Front 99

99. Collagen found in fibrous caps of plaques comes from where, and how is it degraded?

Back 99

Is produced by smooth muscle cells and degraded by action of metalloproteinases.

Metalloproteinases are elaborated by macrophages and atheroma.

Front 100

100. Adrenergic stimulation and correlations between timing of MI's

Back 100

Can elevate physical stresses on the plaque thru systemic hypertension or local vasospasm.

This is the reason why most MI's occur in the morning; due to the extra sympathetic stimulation upon awakening.

Front 101

101. What degree of stenosis is most commonly associated w/plaque disruption?

Back 101

50% or less

Front 102

102. What are 4 indicators of inflammation associated w/plaque disruption?

Back 102

1. Increased adhesion proteins expressed in endothelial cells (ICAM-1, VCAM-1, E-selectin, P-selectin)
2. Accumulation of T cells and macrophages in arterial wall
3. Presence of cytokines (TNF, IL-6, and IFN-γ)
4. High levels of metalloproteinases

Front 103

103. What is C-reactive protein (CRP)

Back 103

Acute phase reactant made in the liver that has been suggested as a predictor of risk of coronary heart disease.

It could be used to estimate the risk of MI in pts w/angina, and the risk of new infarcts in pts who are infarct survivors.

Front 104

104. What is a mural thrombus?

Back 104

Incomplete thrombus; may wax and wane with time.

Can embolize from a coronary artery; it is a potent activator of multiple growth related signals in smooth muscle cells which can contribute to the growth of atherosclerotic lesions.

Front 105

105. What 4 vasoconstrictive things can contribute to plaque disruption?

Back 105

Compromises lumen size and by increasing local mechanical forces; can potentiate plaque disruption stimulated by:

1. Circulating adrenergic agonists
2. Locally released platelet contents
3. Impaired secretion of endothelial cell relaxing factors relative to contractive factors due to atheroma associated endothelial dysfunction
4. Mediates released from perivascular inflammatory cells.

Front 106

106. What is stable angina?

Back 106

Results from increases in Mvo2 that outstrip the ability of markedly stenosed coronary arteries to increase O2 deliver but is not usually associated with plaque disruption.

Front 107

107. What is unstable angina?

Back 107

Derives from sudden change in plaque morphology; which induces partially occlusive platelet aggregation or mural thrombus and vasoconstriction leading to severe but transient reductions in coronary blood flow.

Front 108

108. What is sudden cardiac death?

Back 108

Frequently involves a coronary lesion in which disrupted plaque and often partial thrombus and possible embolus have led to regional myocardial ischemia that induces a fatal ventricular arrhythmia.

Front 109

109. What is angina pectoris?

Back 109

Symptom complex of ischemic heart disease characterized by paroxysmal and usually recurrent attacks usually of substernal or precordial chest discomfort (described as constricting, squeezing, choking, or knifelike)

Caused by transient myocardial ischemia that falls short of inducing cellular necrosis but defines MI.

Front 110

110. Three overlapping patterns of angina pectoris

What are they caused by?

Back 110

1. Stable or typical angina
2. Prinzmetal's or variant angina
3. Unstable or crescendo angina

Caused by varying combos of increased myocardial demand and decreased myocardial perfusion owing to fixed stenosing plaques, disrupted plaques, vasospasms, thrombosis, platelet aggregation, and embolization.

Front 111

111. What is stable angina?

Back 111

AKA typical angina pectoris b/c it is the most common form.

It is caused by reduction of coronary blood perfusion to a critical level by chronic stenosing, coronary atherosclerosis.

It is usually relieved by rest or nitro.

Also, local vasospasm may contribute to imbalance between supply and demand.

Front 112

112. Prinzmetal's variant angina

Back 112

Uncommon pattern of episodic angina that occurs at rest and is due to coronary artery spasm.

Usually have elevated ST segment indicative of transmural ischemia

Anginal attacks are unrelated to physical activity, HR, or BP

Treatment includes nitro and calcium channel blockers.

Front 113

113. Crescendo or unstable angina

Back 113

Pattern of pain that occurs w/progressively increasing frequency.

Is precipitated w/progressively less effort, often occurs at rest, and tends to be of more prolonged duration.

It is sometimes referred to as "pre-infarction" angina

Front 114

114. What is a transmural MI?

Back 114

Most MI's are of this type; ischemic necrosis involves the full or nearly full thickness of the ventricular wall and the distribution of a single coronary artery.

Usually associated w/coronary atherosclerosis, acute plaque change, and superimposed thrombosis

Front 115

115. What is a subendocardial MI (AKA non-transmural MI)?

Back 115

Area of ischemic necrosis limited to inner 1/3 or at most 1/2 of ventricular wall.

Under some circumstances it may extend laterally beyond the perfusion territory of a single coronary artery.

It can occur as a result of plaque disruption, followed by coronary thrombus that becomes lysed before myocardial necrosis extends across the major thickness of the wall.

Can also result from sufficiently prolonged and severe reduction in systemic BP

Front 116

116. Incidence and risk factors of MI

Back 116

Can occur at any age but freq arises w/increasing age w/predispositions to atherosclerosis (hyeprtension, smoking, diabetes, hypercholesterolemia, and hyperlipoprotenia)

Men have increased risk compared to women but this difference declines w/advancing age

Decreasing estrogen in women following menopause (HRT does not protect against MI)

Front 117

117. Sequence of event in typical MI

(Five of them)

Back 117

1. Initial event is sudden change in the morphology of atheromatous plaque
2. Platelets undergo adhesion, aggregation, activation, and release of potent aggregators
3. Vasospasm stimulated by platelet aggregation and release of mediators
4. Other mediators activate extrinsic pathway of coagulation, adding to bulk of thrombus
5. Thrombus evolves to completely occlude the lumen of coronary vessel

Front 118

118. Associated mechanisms in acute transmural MI that are not associated w/plaque thrombus

Back 118

1. Vasospasm
2. Emboli from left atrium associated w/atrial fibrillation
3. Unexplained

Front 119

119. Three myocardial responses to MI

Back 119

1. Biochemical
-cessation of aerobic glycolysis within seconds leading to inadequate production of high energy phosphates and accumulation of breakdown products

2. Functional
-Myocardial function is extremely sensitive to severe ischemia; loss of contractility occurs w/in 60 s of onset

3. Ultrastructural changes
-Myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling

Early changes are potentially reversible

Front 120

120. Prominent mechanism of cell death following MI

Back 120

***Coagulative necrosis

Apoptosis may also be important but are uncertain about this.

Necrosis begins approx 30 min after coronary occlusion

If restoration of blood flow (reperfusion) follows briefer periods of blood interruption (<20min) loss of cell viability can be prevented.

Front 121

121. Irreversible injury of ischemic myocytes - where does it occur first?

Back 121

First occurs in subendocardial zone; with this extended ischemia, a wave front of cell death moves thru the myocardium to involve progressively more of the transmural thickness of the ischemic zone.

Front 122

122. Factors that determine location, size, and morphological features of acute MI

Seven of them...

Back 122

1. Location, severity, and rate of devel of coronary atherosclerotic obstruction
2. The size of the vascular bed perfused by the obstructed vessel
3. Duration of the occlusion
4. Metabolic/oxygen needs of myocardium at risk
5. Extent of collateral blood vessels
6. Presence, site and severity of coronary arterial spasm
7. Other factors such as alterations in blood pressure, HR, and cardiac rhythm

Front 123

123. Infarct modification by reperfusion

Back 123

Best accomplished by restoration of coronary blood flow via thrombolysis, balloon angioplasty, or coronary artery bypass graft.

Front 124

124. Compare and contrast reperfusion therapies

Back 124

Thrombolysis can remove thrombus occluding CA, but does not significantly alter underlying disrupted atherosclerotic plaque that initiated it

PTCA eliminates thrombotic occlusion and can relieve some of the original obstruction caused by plaque

CABG provides flow around the obstruction

Front 125

125. What are the frequencies of critical narrowing and thrombosis of the LAD? What part of the heart is damaged?

Back 125

LAD (40-50%); infarct typically involves the anterior wall of left ventricle near apex; anterior portion of ventricular septum; apex circumferentially.

Front 126

126. What are the frequencies of critical narrowing and thrombosis of the RCA? What part of the heart is damaged?

Back 126

RCA (30-40%); infarct involves inferior/posterior wall of left ventricle; posterior portion of ventricular septum; inferior/posterior right ventricular free wall in some cases.

Front 127

127. What are the frequencies of critical narrowing and thrombosis of the LCX? What part of the heart is damaged?

Back 127

LCX (15-20%); infarct involves lateral wall of left ventricle except apex.

Front 128

128. What is TTC?

Back 128

Immersion of tissue slices of the heart in a solution of triphenyltetrazolium chloride (TTC) can impart a brick-red color to intact, noninfarcted myocardium where the dehydrogenase enzymes are preserved.

B/c dehydrogenases are depleted in the area of ischemic necrosis, an infarcted area is revealed as an unstained pale zone (while old scarred infarcts appear white and glistening).

Front 129

129. What are the EM features during the reversible phase post MI? (W/in first 30 min)

Back 129

Glycogen depletion, mitochondrial swelling and relaxation of myofibrils

Front 130

130. What are the EM features during the irreversible phase post MI? (After first 30 min)

Back 130

Sarcolemmal disruption, mitochrondrial amorphous densities

Front 131

131. What are contraction bands?

Back 131

Visible on microscopic exam of post MI myocardium

Are intensely eosinophilic transverse bands composed of closely packed hypercontracted sarcomeres most likely produced by exaggerated contraction of myofibrils at the instant perfusion is re-established at which time internal portions of an already dead cell w/damaged membranes are exposed to high concentration of calcium ions from plasma.

Front 132

132. Clinical features of MI

Four...

Back 132

Diagnosed by typical symptoms, biochemical evidence and ECG pattern

1. Rapid weak pulse and often profuse sweating
2. Dyspnea due to impaired contractility of ischemic myocardium
3. Q waves post MI
4. Increased blood concentrations of myoglobin, cardiac troponins T and I, creatine kinase, lactate dehydrogenase, and many others

Front 133

133. Changes in biochemical markers with MI

Which is the preferred biomarker?

Back 133

Rise in CK-MB 2-4 hrs after onset of MI; peaks at about 24 hrs and returns to normal w/in approx 72 hrs.

***The preferred biomarkers for MI damage are cardiac-specific proteins, particularly Troponin-I (TnI) and Troponin-T.

Troponin levels increase 2-4 hours after MI, peak at 48 hours, and remain elevated for approx 10 days after MI

Front 134

134. Consequences and or complications of MI

Back 134

1. Contractile dysfunction
2. Arrythmias
3. Myocardial rupture
4. Pericarditis
5. Right ventricular infarction
6. Infarct extension
7. Infarct expansion
8. Mural thrombus
9. Ventricular aneurysm
10. Papillary muscle dysfunction
11. Progressive right heart failure

Front 135

135. Anterior vs. Posterior infarcts

Which one has a worse prognosis?

Back 135

Patients w/anterior infarcts have substantially worse prognosis than those w/posterior infarcts

Front 136

136. What is ventricular remodeling?

Back 136

oth necrotic zone and non-infarcted segments of the ventricle undergo progressive changes in size, shape, and thickness comprising early wall thinning, healing, hypertrophy and dilation, and late aneurysm formation.

Clearly, the initial compensatory hypertrophy of noninfarcted myocardium is hemodynamically beneficial. However, the adaptive effect of remodeling may be overwhelmed by expansion and ventricular aneurysm or late depression of regional and global contractile function owing to changes in viable myocardium.

Front 137

137. What is chronic ischemic heart disease (CIHD)?

Back 137

AKA ischemic cardiomyopathy

Usually constitutes post infarction cardiac decomp owing to exhaustion of the compensatory hypertrophy of non-infarcted viable myocardium that is itself in jeopardy of ischemic injury

Dx rests largely on exclusion of other forms of cardiac involvement

Front 138

138. What is the morphology of CIHD?

Back 138

The heart is usually enlarged and heavy, secondary to left ventricular hypertrophy and dilation.

Invariably there is moderate to severe stenosing atherosclerosis of the coronary arteries and sometimes total occlusion.

Discrete, gray-white scars of healed infarcts are usually present. The mural endocardium is generally normal except for some superficial, patchy, fibrous thickenings, although mural thrombi may be present.

Front 139

139. What are the three major microscopic findings of CIHD?

Back 139

1. Myocardial hypertrophy
2. Diffuse subendocardial vacuolization
3. Scars of previously healed infarcts

Front 140

140. What is sudden cardiac death?

What are 8 of the non-atherosclerotic causes?

Back 140

Often a complication and first clinical manifestation of ischemic heart disease

With decreasing age of victim, the following non-atherosclerotic causes become increasingly possible:
1. Congenital/structural or coronary arterial abnormalities
2. Aortic valve stenosis
3. Mitral valve prolapse
4. Myocarditis
5. Dilated or hypertrophic cardiomyopathy
6. Pulmonary hypertension
7. Hereditary or acquired abnormalities of cardiac conduction system
8. Isolated hypertrophy, hypertensive, or unknown cardiac event

Front 141

141. What is the ultimate mechanism of sudden cardiac death?

Back 141

***Lethal arrythmia***, although ischemic injury can impinge upon the conduction system and create electrocardiac instability

In most cases, fatal arrythmia is triggered by electrical irritability of myocardium that may be distant from the conduction system induced by ischemia or other cellular induced abnormalities

Front 142

142. What is Romano-Ward syndrome?

Back 142

Romano-Ward syndrome is the most important cause of arrhythmias in the absence of structural cardiac pathology.

It is autosomal dominant; long Q-T syndrome which causes heightened cardiac excitability and episodic ventricular arrythmias

Front 143

143. Systemic hypertensive heart disease

Involves which side of the heart?

What are the minimal criteria for Dx?

Back 143

Left sided;

Minimal criteria for Dx:
1. Left ventricular hypertrophy in absence of other cardiovascular pathology that might have induced it
2. History of pathological evidence of hypertension

Front 144

144. What is the morphology of systemic hypertensive heart disease?

Back 144

Hypertension induces left ventricular pressure overload hypertrophy w/o dilation of the left ventricle. The thickening of the left ventricular wall increases the ratio of its wall thickness to radius, and increases the weight of the heart disproportionately to the increase in overall cardiac size.

In time, the increased thickness of the left ventricular wall imparts a stiffness that impairs diastolic filling. This often induces left atrial enlargement.

Front 145

145. What are the microscopic features of systemic hypertensive heart disease?

Back 145

Microscopically, the earliest change of systemic HHD is an increase in the transverse diameter of myocytes, which may be difficult to appreciate on routine microscopy.

At a more advanced stage, the cellular and nuclear enlargement becomes somewhat more irregular, with variation in cell size among adjacent cells, and interstitial fibrosis.

Front 146

146. What are the 4 possible outcomes of systemic hypertensive heart disease?

Back 146

1. The pt may enjoy life and die of unrelated causes
2. The pt may develop progressive IHD owing to the effects of hypertension in potentiating coronary atherosclerosis
3. The pt may suffer progressive renal damage or cerebrovascular stroke
4. The pt experiences progressive heart failure.

Effective control of hypertension can prevent or lead to regression of cardiac hypertrophy and its associated risks.

Front 147

147. What is compensated hypertensive heart disease?

Back 147

May be asymptomatic and suspected only in the appropriate clinical setting by ECG or echocardiographic indications of left ventricular enlargement

Other causes for such hypertrophy must be excluded

Front 148

148. Cor pulmonale

Left or right sided?

Back 148

AKA pulmonary hypertensive heart disease

Consists of right ventricular hypertrophy, dilation, and potentially failure secondary to pulmonary hypertension caused by disorders of the lungs or pulmonary vasculature

Right sided counterpart of systemic hypertensive heart disease

May be acute or chronic depending on suddenness of development of hypertension

Front 149

149. Acute cor pulmonale

vs

Chronic cor pulmonale

Back 149

Acute:
Follows massive pulmonary embolism, and there is marked dilation of the right ventricle w/o hypertrophy.

Chronic:
*Usually implies right ventricular hypertrophy* secondary to prolonged pressure overload caused by obstruction of the pulmonary arteries or arterioles or compression or obliteration of septal capillaries

Front 150

150. What is valvular stenosis vs. valvular insufficiency?

Back 150

Stenosis is the failure of a valve to open completely, thereby impeding forward flow.

Insufficiency, in contrast, results from failure of a valve to close completely, thereby allowing reversed flow.

These abnormalities can be either pure, when only stenosis or regurgitation is present, or mixed, when both stenosis and regurgitation coexist in the same valve, but one of these defects usually predominates.

Front 151

151. What are the 2 things that can cause functional regurgitation?

Back 151

Functional regurgitation results when a valve becomes incompetent owing to either:
1. Dilation of the ventricle, which causes the right or left ventricular papillary muscles to be pulled down and outward, thereby preventing coaptation of otherwise intact mitral or tricuspid leaflets during systole
2. Dilation of the aortic or pulmonary artery, pulling the valve commissures apart and preventing full closure of the aortic or pulmonary valve cusps.

Front 152

152. What are the most important clinical consequences of valvular dysfunction?

Back 152

Most important are the myocardial hypertrophy and the pulmonary and systemic changes.

Moreover, a patch of endocardial thickening often occurs at the point where a jet lesion impinges, such as the focal endocardial fibrosis in the left atrium secondary to a regurgitant jet of mitral insufficiency.

Front 153

153. What are the most frequent causes of valvular abnormalities?

Back 153

Most frequent are acquired stenoses of the aortic and mitral valves, which account for approx 2/3rds of all disease.

Front 154

154. What causes valvular stenosis?

Back 154

*Valvular stenosis is almost always due to a primary cuspal abnormality and is virtually always a chronic process.

Front 155

155. What causes valvular insufficiency?

Back 155

Valvular insufficiency on the other hand may result from either intrinsic disease of the valve cusps or damage to or distortion of the supporting structures (e.g., the aorta, mitral annulus, tendinous cords, papillary muscles, ventricular free wall) without primary changes in the cusps.

It may appear acutely, as w/rupture of cords, or chronically with leaflet scarring and retraction.

Front 156

156. What are the most freq causes of aortic insufficiency?

Back 156

Dilation of the ascending aorta, related to hypertension and aging

Front 157

157. What are the most freq causes of aortic stenosis?

Back 157

Calcification of anatomically normal and congenitally bicuspid aortic valves

Front 158

158. What are the most freq causes of mitral insufficiency?

Back 158

Myxomatous degeneration (mitral valve prolapse)

Front 159

159. What are the most freq causes of mitral stenosis?

Back 159

Postinflammatory scarring (rheumatic heart disease)

Front 160

160. Where in the heart valves are they subject to repetitive mechanical stresses?

Back 160

At the hinge points at the cusps and leaflets.

This is b/c each are subject to
1. 40 million or more cardiac cycles per year
2. Substantial tissue deformations at each cycles
3. Transvavlvular pressure gradients in the closed phase of approximately 120 mm for the mitral and 20 mm for the aortic valve.

Front 161

161. What is a consequence of these repetitive mechanical stresses?

Back 161

It is therefore not surprising that these normally delicate structures suffer cumulative damage complicated by formation of calcific deposits (composed of calcium phosphate material), which may lead to clinically important disease.

*The most freq calcific valvular disease are calcific aortic stenosis, calcification of a congenitally bicuspid aortic valve, and mitral annular calcification.

Front 162

162. What is calcific aortic stenosis?

Back 162

Calcific aortic stenosis is the most common of all valvular abnormalities.

It is usually the consequence of calcification owing to progressive and advanced age-associated "wear and tear" of either previously anatomically normal aortic valves or congenitally bicuspid valves (which approx 1% of the population is born).

Front 163

163. When does aortic stenosis come to clinical attention?

Back 163

Aortic stenosis comes to clinical attention primarily in the 6th to 7th decades of life w/congenitally bicuspid valves but not until the 8th and 9th decades with previously normal valves; hence the term senile calcific aortic stenosis is used to describe the latter condition.

Front 164

164. What is the morphologic hallmark of non-rheumatic, calcific aortic stenosis?

Back 164

The morphologic hallmark is heaped-up calcified masses w/in the aortic cusps that ultimately protrude thru the outflow surfaces into the sinuses of Valsalva, preventing the opening of the cusps.

Front 165

165. What is the morphology of calcific aortic stenosis?

Back 165

The calcific deposits distort the cuspal architecture, primarily at the bases. The calcific process begins int the valvular fibrosa, at the points of maximal cusp flexion (the margins of attachment), and the microscopic layered architecture is largely preserved.

In aortic stenosis, the functional valve area is decreased sufficiently to cause measurable obstruction to outflow; this subjects the left ventricular myocardium to progressively increasing pressure overload.

Front 166

166. What is aortic valve sclerosis?

Back 166

An earlier, hemodynamically inconsequential stage of the calcification process is called aortic valve sclerosis.

Front 167

167. What do the valves look like in calcific aortic stenosis?

Back 167

In contrast to rheumatic stenosis, commisural fusion is not a usual feature of degenerative aortic stenosis.

By the time valves w/aortic stenosis are seen at surgical resection or postmortem exam, however, the cusps may be secondarily fibrosed and thickened.

The mitral valve is generally normal in pts with calcific aortic stenosis, although some pts may have direct extension of aortic valve calcific deposits onto the mitral anterior leaflet or independent calcification of the mitral annulus.

Front 168

168. What are the clinical features of calcific aortic stenosis (superimposed on a previously normal or biscuspid aortic valve)?

Back 168

The failure of compensatory hypertrophy mechanisms is heralded by angina (reduced perfusion in hypertrophied myocardium), syncope (and increased risk of sudden death), or CHF.

With onset of such symptoms, and if left untreated, there is a 50% risk of death w/in 2-5 years; urgent surgical valve replacement is clearly indicated.

In contrast, most asymptomatic patients have an excellent prognosis.

Front 169

169. What is calcific stenosis of congenitally bicuspid aortic valve?

Back 169

In a congenitally bicuspid aortic valve, there are only two functional cusps.

The cusps are usually of unequal size, with the larger cusp having a midline raphe, resulting from incomplete separation during development; less frequently the cusps are of the same size and the raphe is absent.

Front 170

170. What is the importance of the raphe?

Back 170

The raphe that represents the incomplete commissure is frequently a major site of calcific deposits.

Front 171

171. What is the prevalence of calcific stenosis of a congenitally biscuspid aortic valve?

Back 171

Occurring w/an estimated freq of approximately 1.4% of live births, bicuspid aortic valves are generally neither stenotic nor symptomatic at birth or throughout early life.

However, they are predisposed to progressive degenerative calcification.

Front 172

172. What are the clinical features of calcific stenosis of a congenitally biscuspid aortic valve?

Back 172

Once stenosis is present, the clinical course is similar to that described for calcific aortic stenosis.

The mitral valve is normal. Bicuspid aortic valves may also become incompetent as a result of aortic dilation, cusp prolapse, or infective endocarditis.

Front 173

173. What is mitral annular calcification?

Back 173

Degenerative calcific deposits can develop in the fibrous ring (annulus) of the mitral valve, visualized on gross inspection as irregular, stony hard, and occasionally ulcerated nodules (2-5 mm in thickness) that lie behind the leaflets.

This process gernally does not affect valvular function. It occurs most commonly in women over age 60 and individuals with myxomatous mitral valve, or elevated left ventricular pressure.

Front 174

174. What are 4 important points to remember about mitral annular calcification?

Back 174

1. Regurgitation can occur from inadequate systolic contraction of the mitral valve ring
2. Stenosis can occur b/c leafelets are unable to open over bulky deposits
3. Nodular calcific deposits can impinge on conduction pathways, causing arrhythmias
4. Rarely, these deposits become a focus for infective endocarditis

Front 175

175. What is myxomatous degeneration of the mitral valve?

Back 175

AKA MVP. In this valvular abnormality, one or both mitral leaflets are "floppy" and prolapse, or balloon back into the left atrium during systole.

It is estimated to affect 3% of more of adults in the US, most often young women. It is one of the most common forms of valvular heart disease.

Front 176

176. What is the morphology of myxomatous degeneration?

Back 176

The characteristic anatomic change in myxomatous degeneration is intercordal ballooning (hooding) of the mitral leaflets or portions thereof. The affected leaflets are often enlarged, redundant, thick, and rubbery. Frequently involved, the tendinous cords are elongated, thinned, and occasionally ruptures.

Annular dilation is characteristic.

Front 177

177. What are the histologic characteristics of myxomatous degeneration?

Back 177

Histologically, the essential change is attenuation of the fibrosa layer of the valve, on which the structural integrity of the leaflet depends, accompanied by focally marked thickening of the spongiosa layer w/deposition of mucoid (myxomatous) material. The collagenous structure of the cords is attenuated.

Front 178

178. What are five secondary changes that reflect the stresses and injury incident to the billowing leaflets in MVP?

Back 178

1. Fibrous thickening of the valve leaflets, particularly where they rub against each other
2. Linear fibrous thickening of the left ventricular endocardial surface where abnormally long cords snap against it
3. Thickening of the mural endocardium of the left ventricle or atrium as a consequence of friction induced injury induced by the prolapsing leaflets
4. Thrombi on the atrial surfaces of the leaflets, particularly in the recesses behind the ballooned cusps, and on the atrial walls these thrombi contact
5. Focal calcifications at the base of the posterior mitral leaflet

Front 179

179. What is the pathogenesis of MVP?

What other conditions does MVP commonly co-occur in?

Back 179

The basis for the changes within the valve leaflets are associated structures is unknown. Favored is the proposition that there is an underlying developmental defect of connective tissue, possibly systemic.

In keeping with this, myxomatous degeneration of the mitral valve is a common feature of Marfan syndrome (caused by mutations in the gene encoding fibrillin-1) and occasionally occurs in other hereditary disorders of connective tissues.

Front 180

180. What are the clinical features of MVP?

Back 180

Mitral valve prolapse is generally asymptomatic and discovered only as a midsystolic click on auscultation.

It can be associated with atypical chest pain, dyspnea, fatigue, or psychiatric manifestations (e.g., depression, anxiety).

Importantly there is an increased risk of:
1. Infective endocarditis
2. Gradual mitral valvular insufficiency to produce CHF
3. Arrhythmias
4. Sudden death

Front 181

181. What is rheumatic fever and rheumatic heart disease?

Back 181

Rheumatic fever is an acute, immunologically mediated, multisystem inflammatory disease that occurs a few weeks following an episode of group A streptococcal pharyngitis.

Acute rheumatic carditis during the active phase of RF may progress to chronic rheumatic heart disease.

Front 182

182. What are the most important consequences of RF?

Back 182

Chronic valvular deformities, characterized principally by deforming fibrotic valvular disease (particularly mitral stenosis), which produces permanent dysfunction and severe, sometimes, fatal, cardiac problems decades later.

Front 183

183. What are the key pathologic features of acute RF?

1/2

Back 183

During acute RF, focal inflammatory lesions are found in various tissues. They are most distinctive within the heart, where they are called Aschoff bodies. They consist of foci of swollen esoinophilic collagen surrounded by lymphocytes (primarily T cells), occasional plasma cells, and plump macrophages called Anitschkow cells (pathognomonic for RF). These distinctive cells have abundant cytoplasm and central round-to-ovoid nuclei in which the chromatin is disposed in a central, slender wavy ribbon (caterpillar cells).

Front 184

184. What are the key pathologic features of acute RF?

2/2

Back 184

During acute RF, diffuse inflammation and Aschoff bodies may be found in any of the three layers of the heart - pericardium, myocardium, or endocardium.

In the pericardium, the inflammation is accompanied by a fibrinous or serofibrinous pericardial exudate, described as a "bread-and-butter" pericarditis, which generally resolves w/o sequelae.

The myocardial involvement - myocarditis - takes the form of scattered Aschoff bodies w/in the interstitial connective tissue, often perivascular.

Front 185

185. What are verrucae?

Back 185

Concomitant involvement of the endocardium and the left-sided valves by inflammatory foci typically results in fibrinoid necrosis w/in the cusps or along the tendinous cords on which sit small vegetations - verrucae - along the lines of closure.

These irregular, warty projections probably arise from the precipitation of fibrin at sites of erosion, related to underlying inflammation and collagen degeneration, and cause little disturbance in cardiac function.

Front 186

186. What are MacCullum plaques?

Back 186

Subendocardial lesions, perhaps exacerbated by regurgitant gets, may induce irregular thickenings called MacCallum plaques, usually in the left atrium.

Front 187

187. What is the morphology of chronic RHD?

1/2

Back 187

Chronic RHD is characterized by organization of acute inflammation and subsequent fibrosis. In particular, the valvular leaflets become thickened and retracted, causing permanent deformity.

***The cardinal anatomic changes of the mitral (or tricuspid) valve are leaflet thickening, commissural fusion and shortening, and thickening and fusion of tendinous cords.***

Front 188

188. What is the morphology of chronic RHD?

2/2

Back 188

In chronic disease, the mitral valve is virtually always abnormal, but involvement of another valve, such as the aortic, may be the most clinically important in some cases.

Microscopically there is diffuse fibrosis and often neovascularization that obliterate the originally layered and avascular leaflet architecture.

Aschoff bodies are replaced by fibrous cars so that diagnostic forms of these lesions are rarely seen in surgical specimens or autopsy tissue.

Front 189

189. What is the most frequent cause of mitral stenosis?

Back 189

RHD is overwhelmingly the most frequent cause of mitral stenosis (99% of cases)

Fibrous bridging across the valvular commissures and calcification create "fish mouth" or "buttonhole" stenoses. With tight mitral stenosis, the left atrium progressively dilates and may harbor mural thrombus either in the appendage or along the wall.

Front 190

190. What is the pathogenesis of acute rheumatic fever and RHD?

Back 190

It is strongly suspected that acute rheumatic fever is a hypersensitivity reaction induced by group A streptococci.

It is thought that antibodies directed against the M proteins of certain strains of streptococci cross-react w/glycoprotein antigens in the heart, joints, and other tissues. The onset of symptoms 2-3 weeks after infection and the absence of streptococci from the lesions support the concept that RF results from an immune response against the offending bacteria.

*The chronic sequelae result from progressive fibrosis due to both healing of the acute inflammatory lesions and the turbulence induced by ongoing valvular deformities.

Front 191

191. What are the 5 major clinical manifestations of rheumatic fever?

Back 191

1. Migratory polyarthritis of the large joints
2. Carditis
3. Subcutaenous nodules
4. Erythema marginatum of the skin
5. Sydenham chorea, a neurologic disorder w/involuntary purposeless, rapid movements

Front 192

192. How is the Dx of rheumatic fever made?

Back 192

The Dx is established by the so-called Jones criteria: evidence of a preceding group A streptococcal infection, w/the presence of two of the major manifestations listed above or one major and two minor manifestations (nonspecific signs and symptoms that include fever, arthralgia, or elevated blood levels of acute phase reactants).

Front 193

193. What are the clinical features of acute rheumatic fever?

Back 193

Acute RF typically occurs 10 days to 6 weeks after an episode of pharyngitis caused by group A streptococci in about 3% of pts. Acute RF appears most often in children between ages 5 and 15, but about 20% of first attacks occur in middle to later life.

*The predominant clinical manifestations are those of arthritis and carditis (arthritis is far more common in adults than in children).

Front 194

194. What are the clinical features related to acute carditis?

Back 194

Clinical features related to acute carditis include pericardial friction rubs, weak heart sounds, tachycardia, and arrhythmias.

The myocarditis may cause cardiac dilation that may evolve to functional mitral valve insufficiency or even heart failure.

Front 195

195. What are the complications that can result from acute rheumatic fever?

Back 195

After an initial attack, there is increased vulnerability to reactivation of the disease with subsequent pharyngeal infections, and the same manifestations are likely to appear with each recurrent attack.

Carditis is likely to worsen w/each recurrence, and damage is cumulative. Other hazards include embolization from mural thrombi, primarily w/in the atria or their appendages, and infective endocarditis superimposed on deformed valves.

Front 196

196. When does chronic rheumatic carditis occur?

What other complications can result from RF?

Back 196

Chronic rheumatic carditis usually does not cause clinical manifestations for years or even decades after the initial episode of RF. The signs and symptoms of valvular disease depend on which cardiac valves are vinovled.

In addition to various cardiac murmurs, cardiac hypertrophy and dilation, and heart failure, pts w/chronic rheumatic heart disease may suffer from arrhythmias (particularly atrial fibrillation in the setting of mitral stenosis).

Front 197

197. What is infective endocarditis?

Back 197

Infective endocarditis, one of the most serious of all infections, is characterized by colonization or invasion of the heart valves or the mural endocardium by a microbe, leading to the formation of bulky, friable vegetations composed of thrombic debris and organisms, often associated w/destruction of the underlying cardiac tissues.

The aorta, aneurysmal sacs, other blood vessels, and prosthetic devices can also become infected.

*Most cases are bacterial (bacterial endocarditis).

Front 198

198. What is acute endocarditis?

What is subacute endocarditis?

Back 198

Acute endocarditis describes a destructive, tumultuous infection, frequently of a previously normal heart valve, w/a highly virulent organism, that leads to death within days to weeks of more than 50% of pts despite antibiotics and surgery.

In such cases, the disease may appear insidiously and, even untreated, pursue a protracted course of weeks to months (subacute endocarditis).

Front 199

199. What are the different clinical effects of the highly virulent organisms in acute endocarditis vs. the lower virulence organisms of subacute disease?

Back 199

The highly virulent organisms of acute endocarditis tend to produce necrotizing, ulcerative, invasive valvular infections that are difficult to cure by antibiotics and usually require surgery.

In contrast, the lower virulence organisms of subacute disease are less destructive than those of acute endocarditis, and the vegetations often show evidence of healing.

Front 200

200. What causes acute infective endocarditis?

Back 200

Acute infective endocarditis is caused by highly virulent organisms (e.g., Staphylococcus aureus), often seeding a previously normal valve to produce necrotizing, ulcerative and invasive infections.

Clinically, there is a rapidly developing fever w/rigors, malaise, and weakness. Larger vegetations can cause embolic complications; splenomegaly is common.

Front 201

201. What causes subacute infective endocarditis?

Back 201

Subacute infective endocarditis is typically caused by moderate to low virulence organisms (frequently Streptococcus viridans) seeding an abnormal or previously injured valve.

There is less valvular destruction than acute infective endocarditis.

This pattern occurs insidiously w/nonspecific malaise, low-grade fever, weight loss, and a flu-like syndrome. Vegetations tend to be so small that embolic complications occur less frequently.

Front 202

202. What is the pathogenesis of infective endocarditis?

Back 202

Blood-borne organisms, usually bacteria, are prerequisites for infective endocarditis. Seeding of the blood with microbes is the foremost factor.

They can come from infections elsewhere in the body, IV drug abuse (S. aureus!), dental or surgical procedures, or otherwise trivial injury to gut, urinary tract, oropharynx, or skin.

Contributory conditions include neutropenia and immunosuppression.

Front 203

203. What is the morphology of infective endocarditis?

Back 203

In both the acute and subacute forms of the disease, friable, bulky, and potentially destructive vegetations containing fibrin, inflammatory cells, and bacteria or other organissm are present on the heart valves.

*The aortic and mitral valves are the most common sites of infection, although the valves of the right heart may also be inovlved, particularly in IV drug abusers.

The vegetations may be single or multiple and may involve more than one valve.

Front 204

204. What is a ring abscess?

What about the vegetations in fungal endocarditis?

Back 204

Vegetations sometimes erode into the underlying myocardium to produce an abscess cavity called a ring abscess, one of the several important complications.

*Note: fungal endocarditis tends to cause larger vegetations than does bacterial infection.

Front 205

205. What is the morphology subacute endocarditis?

Back 205

The vegetations of subacute endocarditis are associated w/less valvular destruction than those of acute endocarditis, although the distinction between the two forms may be difficult.

Microscopically, the vegetations of typical subacute IE often have granulation tissue at their bases (suggesting chronicity).

With the passage of time, fibrosis, calcification, and a chronic inflammatory infiltrate may develop.

Front 206

206. What are 3 important things to remember regarding the clinical features of infective endocarditis?

Back 206

1. Direct injury to valves *causing insufficiency with CHF) or myocardium and aorta (causing ring abscess or perforation)
2. Emboli from vegetations to spleen, kidneys, heart, and brain with infarction or metastatic infection (septic infarct)
3. Renal injury, including embolic infarction or infection and antigen-antibody complex-mediated glomerulonephritis with nephrotic syndrome, renal failure, or both.

Front 207

207. What is the Duke criteria?

Back 207

The Duke criteria provide a standardized assessment of pts with suspected IE that integrates factors predisposing pts to the development of IE, blood culture evidence of infection, ECK findings, and clinical and laboratory information in assessing pts with potential IE.

Dx by these guidelines often requires either pathologic or clinical criteria. If clinical criteria are used, 2 major, 1 major, +3 minor, or 5 minor criteria are required for Dx.

Front 208

208. What are the minor features included in the Dx of infective endocarditis?

Back 208

They include petechiae, red, linear, or flame-shaped streakes in the nail bed of the digits (splinter or subungual hemorrhages), erythematous or hemorrhagic nontender lesions on the palms or soles (Janeway lesions), subcutaneous nodules in the pulp of the digits (Osler nodes)

Also included are retinal hemorrhages (Roth spots) in the eyes owing to the shortened clinical course of the disease as a result of antibiotic therapy.

Front 209

209. What is nonbacterial thrombotic endocarditis (NBTE)?

Back 209

NBTE is characterized by the deposition of small masses of fibrin, platelets, and other blood components on the leaflets of the cardiac valves.

***In contrast to the vegetations of IE, the valvular lesions of NBTE are sterile and do not contain microrganisms.***

Front 210

210. When does NBTE occur?

Back 210

NBTE is often encountered in debilitated patients, such as those w/cancer or sepsis.

Although the local effect on the valves is usually unimportant, NBTE may achieve clinical significance by producing emboli and resultant infarcts int eh brain, heart, or elsewhere.

Front 211

211. What is the morphology of NBTE?

Back 211

In contrast to IE, the vegetations of NBTE are sterile, nondestructive, and small (1-5 mm), and occur singly or multiply along the line of closure of the leaflets or cusps.

Histologically, they are composed of bland thrombus w/o accompanying inflammatory reaction or induced valve damage. Should the pt survive the underlying disease, organization may occur, leaving delicate strands of fibrous tissue.

Front 212

212. What is the pathogenesis of NBTE?

Back 212

NBTE frequently occurs concomitantly w/venous thromboses or pulmonary embolism, suggesting a common origin in a hypercoagulable state with systemic activation of blood coagulation such as disseminated intravascular coagulation.

This may be unrelated to some underlying disease, such as cancer, and in particular, mucinous adenocarcinomas of the pancreas.

The striking association with mucinous adenocarcinomas may relate to the procogulant effect of circulating mucin, and thus NBTE can be a part of the Trousseau syndrome.

Front 213

213. In what other conditions does NBTE occur?

Back 213

NBTE is also seen occasionally in association w/nonmucin-producing malignancy, such as acute promyelocytic leukemia, and in other debilitating diseases or conditions promoting hypercoagulability.

Endocardial trauma, as from an indwelling catheter, is also a well-recognized predisposing condition, and one freq notes right-sided valvular and endocardial thrombotic lesions along the track of a Swan-Ganz pulmonary artery catheter.

Front 214

214. What is endocarditis of SLE (Libman-Sacks disease)?

Back 214

In SLE, mitral and tricuspid valvulitis w/small, sterile vegetations, called Libman-Sacks endocarditis is occasionally encountered.

Front 215

215. What is the morphology of endocarditis of SLE (Libman-Sacks disease)?

Back 215

The lesions are small single or multiple, sterile, granular pink vegetations ranging from 1-4 mm in diameter. The lesions may be located on the undersurfaces of the AV valves, on the valvular endocardium, on the cords, or on the mural endocardium of atria or ventricles.

*Histologically, the verrucae consist of a finely granular, fibrinous eosinophilic material that may contain hematoxylin bodies (the tissue equivalent of the lupus erythematosus cell of the blood and bone marrow).

An intense valvulitis may be present, characterized by fibrinoid necrosis of the valve substance that is often contiguous w/the vegetation.

Front 216

216. What is the significance of antiphospholipid syndrome?

Back 216

Thrombotic heart valve lesions w/sterile vegetations or rarely fibrous thickening commonly occur w/the antiphospholipid syndrome.

Circulating antiphospholipid antibodies are also commonly associated w/venous or arterial thrombosis, recurrent pregnancy loss, or thrombocytopenia. The mitral valve is more freq involved than the aortic; regurgitation is the usual functional abnormality.

Front 217

217. What is carcinoid heart disease?

Back 217

Carcinoid heart disease is the cardiac manifestation of the systemic syndrome caused by carcinoid tumors. It involves the endocardium and valves of the right heart.

Cardiac lesions are present in one half of pts with the carcinoid syndrome which is characterized by episodic flushing of the skin, cramps, nausea, vomiting, and diarrhea.

Front 218

218. What is the morphology of carcinoid heart disease?

Back 218

The cardiovascular lesions associated w/the carcinoid syndrome are distinctive, consisting of fibrous intimal thickenings on the inside surfaces of the cardiac chambers and valvular leaflets.

The are located mainly in the right ventricle, tricuspid, and pulmonic valves, and occasionally in the major blood vessels. The endocardial plaquelike thickening are composed predominantly of smooth muscle cells and sparse collagen fibers embedded in an acid mucopolysaccharide-rich matrix material. Elastic fibers are not present.

Front 219

219. The clinical and pathologic findings of carcinoid heart disease relate to...?

Back 219

Relate to the elaboration by carcinoid tumors of a variety of bioactive products, such as serotonin, kallikrein, bradykinin, histamine, prostaglandins, and tachykinins.

Plasma levels of serotonin and urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid correlate with the severity of the right heart lesion.