Pbl Exam 8 Case 1

Front 1

1. What is cardiac failure?

Back 1

Failure of heart to pump enough blood to satisfy needs of the body; can result from any heart condition that reduces the ability of the hear to pump blood.

Cause usually is decreased contractility of the myocardium resulting result from diminished coronary blood flow

Front 2

2. Acute effects of moderate cardiac failure

Back 2

Heart is immediate depressed causing:
1. Reduced cardiac output
2. Damming of blood in the veins (increased venous pressure)

Low cardiac output is still sufficient to sustain life for perhaps a few hours but is likely to be associated w/fainting; this acute phase only lasts for a few seconds b/c sympathetic nerve reflexes occur immediately and compensate to a great extent for the damaged heart.

Front 3

3. How does the body compensate for acute cardiac failure by sympathetic nervous reflexes?

Back 3

Best known of the reflexes is the baroreceptor reflex which is activated by diminished arterial pressure; chemoreceptor reflex, the CNS ischemic response, and reflexes that originate in the damaged heart also contribute.

Sympathetic become strongly stimulated w/in a few seconds and parasympathetic signals become reciprocally inhibited

Front 4

4. What are the effects of sympathetic stimulation on circulation?

Back 4

If ventricular musculature is damaged but still functional, sympathetic stimulation strengthens the damages musculature.

If part is nonfunctional and part is normal, the normal muscle is strongly stimulated by sympathetics; in this way partially compensation for the non functional muscle.

Sympathetic stimulation also increases venous return b/c it increases the tone of most blood vessels of circulation, esp veins, raising the mean systemic venous filling pressure almost 100% above normal

Increased filling pressure greatly increases tendency for blood to flow from the veins back into the heart

Front 5

5. Priming of sympathetic reflexes - how long does it take?

Back 5

They become maximally developed in about 30 seconds

Front 6

6. Semi-chronic state of cardiac failure; characterized by what two events?

Back 6

1. Retention of fluid by the kidneys
2. Varying degrees of recovery of the heart itself over a period of weeks to months

Front 7

7. Effect of low CO on renal function

Back 7

In general, urine output remains reduced below normal as long as the CO and arterial pressure remain significantly less than normal

Urine output does not usually return all the way to normal after an acute MI until the CO and arterial pressure rise all the way back to normal or almost normal

Front 8

8. What is the method/mechanism of venous return increase

Back 8

Increased blood volume increases the mean system filling pressure which increases the pressure gradient for causing the venous flow of blood toward the heart and distends the veins which reduces the venous resistance and allows even mroe ease of flow of blood to the heart.

If the heart is not too damaged, increased venous return can often fully compensate for the hearts diminished pumping ability.

Front 9

9. What are three detrimental effects of excess fluid retention post MI?

Back 9

1. Overstretching of the heart
2. Edema and consequent deoxygenation of the blood
3. Development of extensive edema in most parts of the body

Front 10

10. Why are there limited benefits of excess fluid retention post MI?

Back 10

Because the heart is already pumping at its maximum pumping capacity, this excess fluid no longer has a beneficial effect on the circulation. Instead, severe edema develops throughout the body, which can be very detrimental in itself and can lead to death.

Front 11

11. What is compensated heart failure?

Back 11

Increase in right atrial pressure can maintain the CO at a normal level despite continued weakness of the heart, thus many people have normal resting CO but mildly to moderately elevated right atrial pressures b/c of various degrees of compensated heart failure

These persons not know they have cardiac damage b/c damage have occur a little at a time, and the compensation has occurred concurrently with the progressive stages of damage

Any attempt to perform heavy exercise usually causes immediate return of the symptoms of acute failures b/c the heart is unable to increase its pumping capacity.

Front 12

12. Dynamics of severe cardiac failure

What are the clinical signs?

Back 12

No amount of compensation, either by sympathetic nervous reflexes can make the excessively weakened heart pump a normal CO.

As a consequence, the CO cannot rise high enough to make the kidneys excrete normal quantities of fluid

Therefore, fluid continues to be retained, the person develops more and more edema, and this state of events eventually leads to death

This decompensated heart failure which is clinically detected by bubbling rales in the lungs and dyspnea

Front 13

13. Treatment of decompensation?

Back 13

The decomposition process can often be stopped by:

1. strengthening of the heart esp via the drug digitalis so the heart becomes strong enough to pump adequate quantities of blood required to make the kidneys function normally again

2. Administering diuretic drugs to increase kidney excretion while reducing water and salt intake which brings about a balance between fluid intake and output despite low CO

Front 14

14. What is the MOA of the cardiotonic drugs such as
digitalis?

Back 14

Believed to strengthen heart contractions by increasing the quantities of calcium ions in muscle fibers.

In failing heart, the sarcoplasmic reticulum fails to accumulate normal quantities of calcium, and therefore, cannot release enough calcium ions into the free-fluid compartment of the muscle fibers to cause full contraction of the muscle

One effect of digitalis is to depress the calcium pump of the cell membrane of the cardiac muscle fibers. This pump normally pumps calcium ions out of the muscle.

This allows the muscle fiber intracellular calcium level to rise slightly.

Front 15

15. What is unilateral left heart failure?

Back 15

In a large number of patients, especially those with early acute failure, left-sided failure predominates over rightsided failure

Blood continues to be pumped into lungs w/usual right heart vigor but is not pumped out of the lungs by the left heart into systemic circulation.

Mean pulmonary filling pressure rises; pulmonary vascular congestion and edema occur.

Front 16

16. What is the vicious circle of cardiac deterioration?

Back 16

Low arterial pressure that occurs during shock reduces coronary blood supply. This makes the heart still weaker, which makes arterial pressure still more, which worsens shock, and you die.

In a heart w/an already block major coronary vessel, deterioration sets in when coronary arterial pressure falls below 80-90 mm Hg.

Front 17

17. What procedures can be performed to save patients in cardiogenic shock?

Back 17

Surgically removing the clot in the coronary artery often in combination with CABG or catheterizing the blocked coronary artery and infusing either streptokinase or TPA enzymes the dissolve the clot

Little benefit of these procedures after 3 hours.

Front 18

18. Can acute cardiac failure cause peripheral edema?

Back 18

Almost never causes immediate peripheral edema.

Acute left heart failure can cause rapid congestion of the lungs with deveopment of pulmonary edema and death within minutes to hours

However, either left or right heart failure is very slow to cause peripheral edema.

It often causes a fall in peripheral capillary pressure rather than a rise.

Front 19

19. What is the cause of peripheral edema in non-acute heart failure?

Back 19

After the first day of overall heart failure or right-ventricular heart failure, peripheral edema does begin to occur solely b/c of fluid retention by the kidneys.

The retention of fluid increases the mean systemic filling pressure, resulting in increased tendency for blood to return to the heart.

Thus, the right atrial pressure is elevated and returns the arterial pressure back towards normal.

Therefore, the capillary pressure now also rises markedly, causing loss of fluid into the tissues and development of severe edema.

Front 20

20. What are the three known causes of reduced renal output of urine during cardiac failure?

Back 20

1. Decreased glomerular filtration because of reduced arterial pressure and intense sympathetic constriction of the afferent arterioles of the kidney

2. Activation of the renin-angiotensin system and increased reabsorption of water and salt by the renal tubules

3. Increased aldosterone secretion
-Large quantities of aldosterone are secreted by the adrenal cortex due to the activation of the angiotensin system and b/c of increased potassium ion concentration as a result of heart failure

Front 21

21. Why do elevated adosterone levels lead to antidiuretic hormone secretion?

What is the result of this after cardiac failure?

Back 21

The elevated aldosterone further increases the reabsorption of sodium from the renal tubules. This leads to a secondary increase in water reabsorption for two reasons:

1. As Na is reabsorbed, it reduces the osmotic pressure in the tubules but increases the osmotic pressure in the renal interstitial fluids; these changes promote osmosis of water into the blood.

2. The absorbed Na and anions that go w/the Na, i.e. Cl ions, increase the osmotic concentration oft he extracellular fluid everywhere in the body.

This elicits the antidiuretic hormone secretion by the HPA axis, which promotes a still greater increase in tubular reabsorption of water

Front 22

22. What is Atrial natriuretic factor (ANF)?

Back 22

ANF is a hormone released by the atrial walls of the heart when they become stretched; increases in blood 5-10x due to severe heart failure.

The ANF in turn has a direct effect on the kidneys to increase greatly their excretion of salt and water.

Therefore, ANF plays a natural role to help prevent extreme congestive symptoms during cardiac failure.

Front 23

23. What is acute pulmonary edema in late-stage heart failure?

Back 23

Frequent cause of death in heart failure in patients who have already had chronic heart failure for a long time.

When this occurs in a person w/o new cardiac damage, it usually is set off by some temporary overload of the heart.

Front 24

24. Acute pulmonary edema vicious circle...

Back 24

1. Temp increased load on the already weak ventricle initiates viscous circle; blood begins to dam up in the lungs
2. Increased blood in lungs elevates the pulmonary capillary pressure, and a small amt of fluid begins to transude into the lung tissues and alveoli
3. The increased fluid in lungs diminishes the degree of oxygenation in the blood
4. The decreased O2 in the blood further weakens the heart and arterioles everywhere in body; leading to peripheral vasodilation
5. Peripheral vasodilation increases venous return of blood to even more
6. Increased venous return further increases damming of the blood in the lungs, leading to still more transudation of fluid, more O2 desaturation, more venous return, and so forth.

Front 25

25. What are five types of "heroic" therapeutic measures that can reverse the process of an acute pulmonary edema vicious circle?

Back 25

1. Putting tourniquets on both arms and legs to sequester much of the blood in the veins, and, therefore, decrease the workload on the left side of the heart
2. Bleeding the patient
3. Giving a rapidly acting diuretic, such as furosemide, to cause rapid loss of fluid from the body
4. Giving the patient pure O2 to breath to reverse the blood O2 desaturation
5. Giving the patient a rapidly acting cardiotonic drug, such as digitalis, to strengthen the heart

Front 26

26. What is the cardiac reserve?

Back 26

The max percentage that the cardiac output can increase above normal

In a healthy young adults, it is usually 300-400%;

Athletes: 500-600%

Front 27

27. What can decrease the cardiac reserve?

Back 27

Any factor that prevents the heart from pumping blood satisfactorily will decrease the cardiac reserve.

This can result from ischemic heart disease, primary myocardial disease, vitamin deficiency that affects cardiac muscle, physical damage to the myocardium, valvular heart disease, and many other factors

Front 28

28. Dx of low cardiac reserve

Back 28

Usually can be made by requiring the person to exercise either on a treadmill or by walking up and down steps, either of which requires greatly increased cardiac output

The increased load on the heart rapidly uses up the small amt of reserve that is available, and the CO soon fails to rise high enough to sustain the body's new level of activity

Front 29

29. Acute effects of low cardiac reserve during exercise

Three of them...

Back 29

1. Immediate and sometimes extreme shortness of breath resulting from failure of heart to pump sufficient blood to lungs, causing tissue ischemia and air hunger

2. Extreme muscle fatigue resulting from muscle ischemia, thus limiting the person's ability to continue w/the exercise

3. Excessive increase in heart rate b/c the nervous reflexes to the heart overreact in an attempt to overcome the inadequate CO

Front 30

30. Normal cardiac output and venous return?

Normal right atrial pressure?

Back 30

Normal cardiac output and venous return: 5 L/min

Normal right atrial pressure: 0 mm Hg

Front 31

31. Effect of an acute MI on the right atrial pressure and CO?

Back 31

Cardiac output falls to 2 L/min

Right atrial pressure rises immediately to 4 mm Hg

Front 32

32. Effect of sympathetic reflexes 30 sec after MI on CO, venous return, and right atrial pressure?

Back 32

Increases the mean systemic filling pressure

Cardiac output then increases to 4 L/min

Right atrial pressure rises to 5 mm Hg

Front 33

33. Effect of compensation few days after acute MI on CO, right atrial pressure and renal output?

Back 33

Cardiac output returned to normal: 5 L/min

Right atrial pressure has risen still further to 6 mm Hg

B/c the cardiac output is now normal, renal output is also normal, so that a new state of equilibrated fluid balance has been achieved

Front 34

34. How does decompensation following acute MI occur?

Back 34

Results from the fact that the cardiac output never rises to the critical level of 5 L/min needed to re-establish normal kidney excretion of fluid that would be required to cause balance between fluid input and output.

Leads to vicious circle so that further retention of fluid causes only more severe cardiac edema and a detrimental effect on cardiac output. The condition accelerates downhill until death occurs

Front 35

35. Treatment of decompensated heart disease?

Back 35

Use digitalis to strengthen the heart so that the cardiac output can reach the critical level required for the kidneys to excrete normal amounts of urine.

Causes diuresis due to high fluid output in urine.

Also reduces the mean systemic filling pressure and reduces the right atrial pressure as a result of less fluid buildup and the the circulatory system has now stabilized

Front 36

36. Two causes of high output cardiac failure

Back 36

1. Arteriovenous fistula that overloads the heart b/c of excessive venous return even though the pumping capability of the heart is not depressed

2. Beriberi, in which the venous return is greatly increased b/c of diminished systemic vascular resistance, but at the same time, the pumping capability of the heart is depressed

Front 37

37. What is the normal weight of the heart?

Back 37

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

Front 38

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

Back 38

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 39

39. What does a sarcomere consist of?

Back 39

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 40

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

Back 40

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 41

41. How do atrial myocytes differ from ventricular myocytes?

Back 41

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 42

42. What is ANP?

Back 42

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 43

43. What are intercalated disks?

Back 43

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 44

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

Back 44

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

Front 45

45. What are the three major coronary arteries?

Back 45

1. LAD
2. LCX
3. RCA

Front 46

46. What does the LAD supply?

Back 46

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 47

47. What does the RCA supply?

Back 47

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 48

48. What does the LCX supply?

Back 48

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

Front 49

49. What is the nodule of Arantius?

Back 49

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

Front 50

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

Another ridiculously long list...

Back 50

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 51

51. What are the five principal mechanisms by which cardiovascular dysfunctions occur?

Back 51

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 52

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

Back 52

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 53

53. What is CHF?

Back 53

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 54

54. What are the three main mechanisms by which the cardiovascular system maintains arterial pressure?

Back 54

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 55

55. What causes most instances of heart failure?

Back 55

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

Front 56

56. When does diastolic dysfunction occur?

Back 56

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 57

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

Back 57

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 58

58. What are the early mediators of hypertrophy?

Back 58

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 59

59. Cardiac hypertrophy summary

Back 59

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 60

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

What causes the clinical effects of left-sided CHF?

Back 60

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 61

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

Back 61

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 62

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

Back 62

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

Front 63

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

Back 63

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 64

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

Back 64

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 65

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

Back 65

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

Front 66

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

Back 66

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 67

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

Back 67

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

Front 68

68. What is right-sided heart failure?

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

Back 68

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 69

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

Back 69

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 70

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

Back 70

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

Front 71

71. What are the four major manifestations of right-sided heart failure?

Back 71

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 72

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

Back 72

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

Front 73

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

Back 73

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 74

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

Back 74

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 75

75. What is congenital heart disease?

Back 75

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 76

76. What are the top three congenital cardiac manifestations?

Back 76

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

Front 77

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

Back 77

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 78

78. What infections can lead to congenital heart disease?

Back 78

Congenital rubella infection

Front 79

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

Back 79

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 80

80. What is NKX2.5?

Back 80

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 81

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

Back 81

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 82

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

Back 82

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 83

83. What are two other common mechanisms of congenital heart disease?

Back 83

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 84

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

Back 84

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 85

85. What are left-to-right shunts?

When are they not surgically correctable?

Back 85

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 86

86. What are the three major left-to-right shunts?

Back 86

1. ASD
2. VSD
3. PDA

Front 87

87. What are ASDs?

Back 87

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 88

88. What are the three types of ASDs?

Back 88

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 89

89. What is the morphology of ASDs?

Back 89

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 90

90. Why do ASDs become symptomatic after age 30?

Back 90

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 91

91. What are VSDs?

Back 91

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 92

92. What are the classifications of the VSDs?

Back 92

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 93

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

Back 93

Infective endocarditis

Front 94

94. What is the clinical course of VSDs?

Back 94

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 95

95. What is a PDA?

Back 95

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 96

96. What are the consequences of PDA?

Back 96

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 97

97. What are right-to-left shunts?

What are the primary and secondary findings in these shunts?

Back 97

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 98

98. What are the three major congenital right-to-left shunts?

Back 98

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

Front 99

99. What is Tetralogy of Fallot?

Back 99

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 100

100. What is the clinical course of Tetralogy?

Back 100

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 101

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

Back 101

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

Front 102

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

Back 102

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 103

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

Back 103

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 104

104. What is the clinical course of TGA?

Back 104

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 105

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

Back 105

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 106

106. What is a persistent truncus arteriosus?

Back 106

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 107

107. What is tricuspid atresia?

Back 107

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 108

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

Back 108

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 109

109. What are the consequences of TAPVC?

Back 109

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 110

110. What are the two classic forms of coarctation of the aorta?

Back 110

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 111

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

Back 111

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 112

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

Back 112

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 113

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

Back 113

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 114

114. What are some common symptoms in all coarctations?

How is it treated surgically?

Back 114

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 115

115. What is pulmonary stenosis and atresia?

Back 115

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 116

116. What is the clinical course of pulmonary stenosis?

Back 116

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 117

117. What are the three types of aortic stenoses?

Back 117

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

Front 118

118. What is valvular aortic stenosis?

Back 118

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 119

119. What is subaortic stenosis?

Back 119

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

Front 120

120. What is supravalvular aortic stenosis?

Back 120

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 121

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

Back 121

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

Front 122

122. What are the clinical features of aortic stenosis?

Back 122

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 123

123. Ischemic heart disease (IHD)

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

Back 123

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 124

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

Back 124

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 125

125. What three conditions aggravate ischemia?

Back 125

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 126

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

Back 126

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

Front 127

127. Epidemiology of IHD

Back 127

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 128

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

Back 128

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 129

129. Pathogenesis of IHD

Back 129

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 130

130. Causes of coronary atherosclerosis

What degrees of stenosis are associated w/clinical symptoms?

Back 130

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 131

131. Common locations of stenosing plaques

Back 131

Can happen anywhere but tend to predominate within:

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

Front 132

132. What is the role of acute plaque change?

Back 132

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 133

133. What are vulnerable plaques?

Back 133

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 134

134. What determines the strength of the fibrous caps?

Back 134

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 135

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

Back 135

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

Metalloproteinases are elaborated by macrophages and atheroma.

Front 136

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

Back 136

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 137

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

Back 137

50% or less

Front 138

138. What are four indicators of inflammation associated w/plaque disruption?

Back 138

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 139

139. What is C-reactive protein (CRP)

Back 139

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 140

140. What is a mural thrombus?

Back 140

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 141

141. What four vasoconstrictive things can contribute to plaque disruption?

Back 141

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 142

142. What is stable angina?

Back 142

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 143

143. What is unstable angina?

Back 143

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 144

144. What is sudden cardiac death?

Back 144

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 145

145. What is angina pectoris?

Back 145

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 146

146. Three overlapping patterns of angina pectoris

What are they caused by?

Back 146

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 147

147. What is stable angina?

Back 147

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 148

148. Prinzmetal's variant angina

Back 148

ncommon 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 149

149. Crescendo or unstable angina

Back 149

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 150

150. What is a transmural MI?

Back 150

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 151

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

Back 151

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 152

152. Incidence and risk factors of MI

Back 152

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 153

153. Sequence of event in typical MI

(Five of them)

Back 153

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 154

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

Back 154

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

Front 155

155. Three myocardial responses to MI

Back 155

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 156

156. Prominent mechanism of cell death following MI

Back 156

***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 157

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

Back 157

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 158

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

Seven of them...

Back 158

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 159

159. Infarct modification by reperfusion

Back 159

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

Front 160

160. Compare and contrast reperfusion therapies

Back 160

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 161

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

Back 161

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

Front 162

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

Back 162

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 163

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

Back 163

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

Front 164

164. What is TTC?

Back 164

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 165

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

Back 165

Glycogen depletion, mitochondrial swelling and relaxation of myofibrils

Front 166

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

Back 166

Sarcolemmal disruption, mitochrondrial amorphous densities

Front 167

167. What are contraction bands?

Back 167

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 168

168. Clinical features of MI

Four...

Back 168

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 169

169. Changes in biochemical markers with MI

Which is the preferred biomarker?

Back 169

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 170

170. Consequences and or complications of MI

Back 170

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 171

171. Anterior vs. Posterior infarcts

Which one has a worse prognosis?

Back 171

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

Front 172

172. What is ventricular remodeling?

Back 172

Both 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 173

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

Back 173

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 174

174. What is the morphology of CIHD?

Back 174

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 175

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

Back 175

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

Front 176

176. What is sudden cardiac death?

What are eight the non-atherosclerotic causes?

Back 176

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 177

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

Back 177

***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 178

178. What is Romano-Ward syndrome?

Back 178

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 179

179. Systemic hypertensive heart disease

Involves which side of the heart?

What are the minimal criteria for Dx?

Back 179

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 180

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

Back 180

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 181

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

Back 181

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 182

182. What are the four possible outcomes of systemic hypertensive heart disease?

Back 182

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 183

183. What is compensated hypertensive heart disease?

Back 183

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 184

184. Cor pulmonale

Left or right sided?

Back 184

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 185

185. Acute cor pulmonale

vs

Chronic cor pulmonale

Back 185

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 186

186. What are the classes of pharmacologic agents that play a role in cardiac contractility?

Back 186

The cardiac glycosides raise intracellular Ca⁺ concentration via inhibition of the sarcolemmal Na⁺/K⁺-ATPase, while β-agonists and phosphodiesterase inhibitors increase intracellular levels of cAMP.

Front 187

187. What is digoxin?

Back 187

Digoxin is a selective inhibtior of the plasma membrane sodium pump. Cardiac myocytes exposed to digoxin extrude less sodium, leading to a rise in intracellular sodium concentration. In turn, the increase in intracellular sodium alters the equilibrium of the sodium-calcium exchanger: calcium efflux is decreased b/c the gradient for sodium entry is decreased, while calcium influx is increased b/c the gradient for sodium efflux is increased.

The net result is arise in the intracellular calcium concentration.

Front 188

188. What is digitoxin?

Back 188

Digitoxin is structurally identical to digoxin except it is less hydrophilic.

Thus, it is metabolized and excreted primarily by the liver; this makes it a suitable alternative to digoxin for the treatment of patients with HF and chronic kidney disease.

However, digitoxin has a VERY long half life (7 days!).

Front 189

189. Digoxin and digitoxin MOA (3 of them)

Back 189

1) In myocardium, inhibit plasma membrane Na⁺/K⁺-ATPase, leading to increased cytoplasmic calcium concentration, which results in positive inotropy.

2. In autonomic nervous system, inhibit sympathetic outflow and increase parasympathetic (vagal) tone

3. At AV node, prolong effective refractory period and slow conduction velocity.

Front 190

190. Digoxin and digitoxin

Back 190

PURPOSE: Systolic heart failure, supraventricular arrhythmias including Afib, atrial flutter, and paroxysmal atrial tachycardia

ADVERSE: Arryhythmias (esp conduction disturbances w/or w/o AV block, PVCs, and SVT; agitation, fatigue, muscle weakness, blurred vision, yellow-green halo around visual images, anorexia, nausea, vomiting

CONTRA: Vfib and Vtach

Front 191

191. What are the five significant drugs interactions for digoxin and digitoxin?

Back 191

Digoxin has numerous significant drug interactions.

1.Coadministration with beta-blockers increases the risk of developing high grade AV block.
2. Beta-blockers and calcium channel blockers counteract positive inotropic effects of digoxin.
3. Potassium wasting diuretics and hypokalemia predispose to digoxin toxicity.
4. Some antibiotics, such as erythromycin, increase digoxin absorption.
5. Coadministration with verapamil, quinidine, or amiodarone can increase digoxin levels.

Front 192

192. Digoxin and digitoxin therapeutic considerations (4)

Back 192

1. Treat digoxin toxicity by normalizing plasma potassium level or using digoxin antibodies in severe cases.
2. Chronic kidney disease requires reduction in loading dose and maintenance dose of digoxin.
3. Digoxin has not been shown to improve survival; it palliates symptoms and improves functional status
4. Digitoxin undergoes hepatic metabolism and biliary excretion

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193. Digoxin immune Fab

Back 193

MOA: Antibody fragment that binds to and inhibits digoxin

PURPOSE: Potentially life-threatening digitalis toxicity; acute digoxin toxicity in which ingested amt or serum digoxin level is unknown

ADVERSE: Heart failure, anaphylaxis

CONTRA: Use w/caution in pts allergic to ovine proteins

NOTES: Keep resuscitation equipment available during administration of digoxin immune Fab.

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194. Dopamine

Back 194

MOA: Increase cAMP levels by activating G protein-coupled adrenergic receptors; acting at cardiac β1 adrenergic receptors, agonists have positive inotropic, chronotropic, and lusitropic effects

PURPOSE: In distributive or cardiogenic shock, use as adjunct to increase CO, BP, and urine flow; Short term treatment of severe, refractory, chronic heart failure

ADVERSE: Bradycardia, asthma attacks, widening of QRS complex, cardiac arrhythmias, hypotension, hypertension, palpitations, tachycardia

CONTRA: Pheochromocytoma, uncorrected tachyarrhythmias, Vfib

NOTES: Coadministration with MOAIs results in decreased metabolism of dopamine which can lead to tachycardia and arrhythmia

Front 195

195. Dopamine doses - what are the effects at low, intermediate, and high doses?

Back 195

1. Low doses cause vasodilation in the periphery by stimulating dopaminergic D1 receptors in renal and mesenteric vascular beds
2. Intermediate doses cause widespread vasodilation via stimulation of D1 receptors, and increased contractility and heart rate via activation of β1 receptors.
3. High doses cause generalized vasoconstriction via stimulation of α1 receptors

Front 196

196. What is dobutamine?

Back 196

Dobutamine is a synthetic sympathomimetic amine that acts as a predominantly β1, modest β2 agonist.

It is the DOC for patients with acute cardiogenic circulatory failure.

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197. Dobutamine

Back 197

MOA: A racemic mixture of enantiomers that have differential effects on adrenoceptor subtypes; overall effect is predominantly β1 and modest β2.

PURPOSE: Short term treatment of cardiac decomp secondary to depressed contractility (cardiogenic shock)

ADVERSE: Same as dopamine, except cardiac arrhythmias occur less freq

CONTRA: Idiopathic hypertrophic subaortic stenosis

NOTES: Sypathomimetic inotrope of choice for pts with acute cardiogenic circulatory failure; dobutamine induces less SVT and high grade ventricular arrhythmia than dopamine.

Front 198

198. Epinephrine

Back 198

MOA: Nonselective agonist at β1, β2, α1, and α2 receptors

PURPOSE: Bronchospasm, hypersensitivity reaction, anaphylactic shock, cardiac resuscitation, hemostasis, prolong local anesthetic effect, open angle glaucoma, nasal congestion

ADVERSE: Arrhythmias including Vfib, cerebral hemorrhage, severe hypertension; headache, nervousness, tremor, palpitations, tachycardia

CONTRA: Active labor, angle-closure glaucoma, shock, organic brain damage, cardiac arrhythmias, coronary insufficiency, severe hypertension, cerebral atherosclerosis

NOTES: *High doses can cause tachycardia and life-threatening arrhythmias.

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199. Norepinephrine

Back 199

MOA: Nonselective agonist at β1, α1, and α2 receptors

PURPOSE: BP support in acute hypotensive states (shock), limit GI bleeding via intraperitoneal or nasogastic administration

ADVERSE: Same as epinephrine

CONTRA: Peripheral vascular thrombosis, profound hypoxia, hypercapnia, hypotension from loss of blood volume

NOTES: May cause tachycardias invovling the SA node or ectopic atrial or ventricular sites in pts with contractile dysfunction; Avoid coadministration with MOAI due to risk of severe hypertension.

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200. Isoproterenol

Back 200

MOA: Nonselective β-agonist at β1 and β2 receptors

PURPOSE: Emergency treatment of arrhythmias (IV), atropine-resistant hemodynamically significant bradycardia (IV); heart block and shock (IV); bronchospasm (inhalation)

ADVERSE: Same as epinephrine

CONTRA: Tachycardia caused by digitalis intoxication; angina pectoris

NOTES: May be useful in treating pts w/β-antagonist overdose and in atropine resistant bradycardia; *Do not administer to pts w/active coronary artery disease!

Front 201

201. What are the names of the four phosphodiesterase inhibitors?

Back 201

1. Theophylline
2. Inamrinone
3. Milrinone
4. Vesnarinone

Front 202

202. What is the MOA of the phosphodiesterase inhibitors?

Back 202

Increase cAMP by inhibiting the PDE enzymes that hydrolyze it.

In cardiac myocytes, PDE inhibitors have postiive inotropic and lusitropic effects.

PDE inhibitors also relax vascular smooth muscle and thereby decrease preload (venodilation ) and afterload (arteriodilation)

Front 203

203. Theophylline
Inamrinone
Milrinone
Vesnarinone

Back 203

PURPOSE: Short-term treatment of severely failing circulation in pts refractory to conventional therapy

ADVERSE: Ventricular arrhythmias, thrombocytopenia (greater incidence w/inamrinone than w/milrinone); reversible neutropenia and agranulocytosis (vesnarinone)

CONTRA: Asthma; do not use these agents in place of surgical intervention in pts with stenotic valvular disease; acute phase of MI

Front 204

204. PDE inhibitors NOTES

Back 204

1. Coadministration with disopyramide may cause severe hypotension
2. Use of inamrinone is limited by 10% occurrence of thrombocytopenia
3. Oral formulation of milrinone is available; milrinone use is associated w/statistically significant increase in mortality in heart failure pts

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205. Levosimendan

Back 205

MOA: Enhances the sensitivity of troponin C to calcium, which increases the extent of actin-myosin interactions w/o a substantial increase in MVO2.

PURPOSE: Not approved for use in teh US, but it can improve cardiac hemodynamics in severe systolic HF and may reduce short term mortality

ADVERSE: Dose-related hypotensiona nd reflex tachycardia, nausea, headache

CONTRA: Hypersensitivity to levosimendan or racemic simendan.