Pbl Exam 8 Case 3

Front 1

1. What is cardiac output?

Back 1

Cardiac output is the quantity of blood pumped into the aorta each minute by the heart.

This is also the quantity of blood that flows through the circulation.

Front 2

2. What is venous return?

Back 2

Venous return is the quantity of blood flowing from the veins into the right atrium each minute.

The venous return and cardiac output must equal each other except for a few heartbeats at a time when blood is temporarily stored in or removed from the heart and lungs.

Front 3

3. What four factors directly affect cardiac output?

Back 3

1. The basic level of body metabolism
2. Whether the person is exercising
3. The person's age
4. Size of the body

Front 4

4. What are the average COs for young healthy men and women?

Back 4

Men: resting CO = 5.6 L/min

Women: resting CO = 4.9 L/min

Avg for resting adult is often stated to be almost exactly 5 L/min

Front 5

5. What is the cardiac index?

Back 5

Cardiac index is the cardiac output per square meter of body surface area

Front 6

6. What is the effect of age on cardiac index?

Back 6

Rising rapidly to 4 L/min/m^2 at age 10, the cardiac index declines to about 2.4 L/min/m^2 at age 80 years.

Avg for an adult is around 2.5-3.5 L/min/m^2

Front 7

7. What primarily controls the cardiac output?

Back 7

The cardiac output is controlled by venous return.

The various factors of the peripheral circulation affect the flow of blood into the heart from the veins, and is called venous return.

This relies on the Frank-Starling law of the heart.

Front 8

8. What is the Frank-Starling law of the heart?

Back 8

When increased quantities of blood flow into the heart, the increased blood stretches the walls of the heart chambers. As a result of the stretch, the cardiac muscle contracts with increased force, and this empties the extra blood that has entered from the systemic circulation.

Front 9

9. What other important factors control the cardiac output?

Back 9

Stretching the heart causes the heart to pump faster. That is, stretch of the sinus node in the wall of the right atrium can increase the HR as much as 10-15%.

In addition, the stretched right atrium initiates a nervous reflex called the Bainbridge reflex, passing first to the vasomotor center of the brain and then back to the heart by way of the sympathetic nerves and vagi, also to increase the HR.

Front 10

10. Summary of cardiac output regulation

Back 10

The venous return to the heart is the sum of all the local blood flows through all the individual tissue segments of the peripheral circulation.

Therefore, it follows that cardiac output regulation is the sum of all the local blood flow regulations.

Front 11

11. What is the relationship between the total peripheral resistance and the cardiac output?

What is the equation for CO?

Back 11

Any time the long term level of total peripheral resistance changes, the cardiac output changes quantitatively in exactly the opposite direction.

CO = (Arterial pressure) / (Total peripheral resistance)

Front 12

12. What factors can cause a hypereffective heart?

Back 12

Only two types of factors usually can make the heart a better pump than normal. They are:

1. Nervous stimulation
2. Hypertrophy of the heart muscle

Front 13

13. What factors cause a hypoeffective heart?

Back 13

Any factor that decreases the heart's ability to pump blood causes hypoeffectivity.

These include:
MI
Inhibition of sympathetic stimulation
Abnormal HR or rhythm
Valvular heart disease
Increased arterial pressure
Congenital heart disease
Myocarditis
Cardiac hypoxia

Front 14

14. What is the role of the nervous system in controlling CO?

Back 14

The nervous system maintains the arterial pressure when the venous return and CO increase.

This maintenance of a normal arterial pressure by nervous reflexes, is essential to achieve high COs when the peripheral tissues dilate their vessels to increase the venous return.

Front 15

15. What happens to the arterial pressure during exercise?

Back 15

During exercise, intense increase in metabolism in muscles acts directly on the muscle arterioles to relax them and to allow adequate oxygenation needed to sustain muscle contraction.

This greatly decreases the total peripheral resistance, which normally would decrease the arterial pressure as well.

However, the nervous system prevents the arterial pressure from falling to disastrously low levels by raising the arterial pressure even above normal to maintain/increase the CO

Front 16

16. What is the one common factor in conditions that commonly cause CO's higher than normal?

Back 16

They all result from chronically reduced total peripheral resistance.

Front 17

17. What are these conditions that decrease the peripheral resistance while at the same time increase the CO?

Back 17

1. Beriberi
-Insufficient thiamine (b1) causes peripheral vasodilation and can increase CO often 2x normal.

2. AV fistula (shunt)

3. Hyperthyroidism
-Oxygen usage increases, and vaodilator products are released from the tissues

4. Anemia
-causes reduced viscosity of the blood and diminished delivery of oxygen to the tissues, which causes local vasodilation.

Front 18

18. What are the two categories of conditions that cause low CO?

Back 18

1. Those abnormalities that cause the pumping effectiveness to fall too low

2. Those that cause venous return to fall too low

Front 19

19. What are the conditions that cause low CO via decreased pumping efficacy?

Back 19

1. Severe coronary blood vessel blockage and consequent MI
2. Severe valvular heart disease
3. Myocarditis
4. Cardiac tamponade
5. Cardiac metabolic derangements

When the cardiac output falls so low, the condition is called cardiac shock.

Front 20

20. What are the conditions that cause low CO via non-cardiac peripheral factors (i.e. decreased venous return)?

Back 20

1. Decreased blood volume- most common factor
2. Acute venous dilation
3. Obstruction of the large veins
4. Decreased tissue mass, especially decreased skeletal muscle mass

When the CO falls so low due to non-cardiac peripheral factors, the person is said to suffer circulatory shock.

Front 21

21. What is the effect of increased external pressure outside the heart on CO curves?

Back 21

The normal external pressure is equal to the intrapleural pressure, which is -4 mm Hg.

A rise in the intrapleural pressure to -2 mm Hg shifts the entire CO curve to the right b/c to fill the cardiac chambers with blood requires an extra 2 mm Hg right atrial pressure to overcome the increased pressure on the outside of the heart.

Likewise, an increase in intrapleural pressure to +2 mm Hg requires further shifts the the right.

Front 22

22. What are five factors that can alter the intrapleural pressure?

Back 22

1. Cyclical changes of intrapleural pressure during respiration, which are about ±2 mm Hg during normal breathing but can be as much as ±50 mm Hg during strenuous breathing
2. Breathing against a negative pressure, which shifts the curve to the left
3. Positive pressure breathing, which shifts the curve to the right
4. Opening the thoracic cage, which increases the intrapleural pressure to 0 mm Hg and shifts the curve to the right
5. Cardiac tamponade, which shifts the curve farther to the right.

Front 23

23. What three principal factors affect venous return to the heart from the systemic circulation?

Back 23

1. Right atrial pressure, which exerts a backward force on the veins to impede flow of blood from the veins into the right atrium.
2. Degree of filling of the systemic circulation (mean systemic filling pressure)
3. Resistance to blood flow between the peripheral vessels and the right atrium

Front 24

24. What is the relationship between venous return and right atrial pressure?

Back 24

If all nervous circulatory reflexes are prevented from acting, venous return decreased to zero when the right atrial pressure rises to about +7 mm Hg.

At this same time, pumping by the heart also approaches zero b/c of decreasing venous return.

Front 25

25. What is mean systemic filling pressure?

Back 25

This is the pressure measured everywhere in the systemic circulation when all flow of blood is stopped.

In other words, this is the pressure at which the arterial and venous pressures come to equilibrium.

Front 26

26. What happens when the atrial pressure becomes more negative?

Back 26

When the right atrial pressure falls below zero, further increase in venous return almost ceases. By the time the right atrial pressure has fallen to about -2 mm Hg, the venous return will have reached a plateau.

It remains at this plateau level even though the atrial pressure falls even further.

Front 27

27. What is the cause of this plateau in venous return?

Back 27

The plateau is caused by collapse of the veins entering the chest.

Negative pressure in the right atrium sucks the walls of the veins together where they enter the chest, which prevents any additional flow of blood from the peripheral veins.

Front 28

28. What is mean circulatory filling pressure?

Back 28

When heart pumping is stopped, flow of blood everywhere in the circulation ceases a few seconds later.

Without blood flow, the pressures everywhere in the circulation become equal. This equilibrated pressure level is called the mean circulatory filling pressure.

Front 29

29. What is the effect of blood volume on mean circulatory filling pressure?

Back 29

The greater the volume of blood in the circulation, the greater is the mean circulatory filling pressure b/c extra blood volume stretches the walls of the vasculature.

Front 30

30. What is the effect of sympathetic nervous stimulation of the circulation on mean circulatory filling pressure?

Back 30

Strong sympathetic stimulation constricts all the systemic blood vessels as well as the larger pulmonary blood vessels and even the chambers of the heart.

Therefore, the capacity of the system decreases, so that at each level of blood volume, the mean circulatory filling pressure is increased.

Front 31

31. How does the mean systemic filling pressure relate to mean circulatory filling pressure?

Back 31

The mean systemic filling pressure is slightly different from the mean circulatory filling pressure.

The mean systemic pressure, is important for determining venous return, but is almost impossible to measure.

The mean systemic filling pressure, however, is almost always nearly equal to the mean circulatory filling pressure b/c the pulmonary circulation has less than 1/8 as much capacitance as the systemic circulation and only about 1/1 as much blood volume.

Front 32

32. How do changes in the mean systemic filling pressure affect the venous return curve?

Back 32

The greater the mean systemic filling pressure, the more the venous return curve shifts upward and to the right.

In other words, the greater the system is filled, the easier it is for blood to flow into the heart. The less the filling, the more difficult it is for blood to flow into the heart.

Front 33

33. What is the pressure gradient for venous return?

Back 33

The greater the difference between the mean systemic filling pressure and the right atrial pressure, the greater becomes the venous return.

Therefore, the difference between these two pressures is called the pressure gradient for venous return.

Front 34

34. What is resistance to venous return?

Back 34

In the same way that meansystemic filling pressure represents a pressure pushing venous blod from teh periphery toward the heart, there is also resistance to this venous flow of blood.

This is called the resistance to venous return.

Front 35

35. Why is the resistance to venous return important?

Back 35

When the resistance in the veins increases, blood begins to be dammed up, mainly in the veins themselves. But the venous pressure rises very little b/c the veins are highly distensible. Therefore, this rise in venous pressure is not very effective in overcoming the resistance, and blood flow into the right atrium decreases drastically.

Conversely, even slight accumulation of blood in the arteries raises the pressure greatly.

Front 36

36. How does one determine the resistance to venous return?

Back 36

About two thirds is determined by venous resistance, and about one third by the arteriolar and small artery resistance.

It can be calculated by:

VR = (Psf - PRA) / RVR

where Psf is mean systemic filling pressure, PRA is right atrial pressure, and RVR is resistance to venous return.

In normal adults, VR = 5 L/min, Psf = 7 mm Hg, PRA = 0 mm Hg, and RVR = 1.4 mm Hg/L

Front 37

37. What is the highest level to which the right atrial pressure can rise?

Back 37

The highest level to which the right atrial pressure can rise, regardless of how much the heart might fail, is equal to the mean systemic filling pressure.

Front 38

38. How does the heart and systemic circulation operate together?

Back 38

1. The venous return from the systemic circulation must equal the CO from the heart

2. The right atrial pressure is the same for both the heart and the systemic circulation

Front 39

39. What is the effect of increased blood volume on CO?

Back 39

A sudden increase in blood volume increases the CO.

Front 40

40. Why does the greatly increased CO caused by increased blood volume only last for a few minute?

Three reasons...

Back 40

Several compensatory effects occur:
1. Increased CO increases the capillary pressure so that fluid begins to transude out of the capillaries, thereby returning the blood volume toward normal

2. The increased pressure in veins causes the veins to continue distending via stress-relaxation, thus reducing the mean systemic pressure

3. The excess blood flow thru the peripheral tissues causes autoregulatory increase in the peripheral resistance, thus increases the resistance to venous return.

Front 41

41. What are the effects of sympathetic stimulation on cardiac output?

Back 41

Sympathetic stimulation:
1. Makes the heart a stronger pump
2. In the systemic circulation, it increases the mean systemic filling pressure b/c of contraction of the peripheral vessels, especially the veins, and it increases the resistance to venous return.

In sum, different degrees of sympathetic stimulation can increase the CO progressively to about 2x normal for short periods of time, until other compensatory effects occur.

Front 42

42. What is the effect of sympathetic inhibition on CO?

Back 42

1. The mean systemic filling pressure falls
2. The effectiveness of the heart as a pump decreases

Front 43

43. What happens when one opens a large AV fistula?

Back 43

1. A sudden large decrease in resistance to venous return
2. A slight increase in the CO b/c opening the fistula decreases the peripheral resistance and allows an acute fall in arterial pressure against which the heart can pump more easily.
3. An increase in right atrial pressure
4. CO raises even further due to hypertrophy of the heart

Front 44

44. What are the two methods used for measuring CO?

Back 44

1. Oxygen Fick method
2. Indicator dilution method

Front 45

45. Oxygen Fick method

Back 45

A catheter is inserted into the right atrium and into the right ventricle or pulmonary artery to obtain mixed venous blood. Systemic arterial blood is obtained from anywhere in the body.

The rate of oxygen absorption by the lungs is measured by the rate of disappearance of oxygen from the respired air.

CO = (O₂ absorbed per min by the lungs) / (AV O₂ difference)

Front 46

46. Indicator dilution method

Back 46

A small amt of indicator (usually dye) is injected into a large systemic vein, or preferably into the right atrium. This passes into the systemic circulation. The concentration of the dye is recorded as the dye passes thru one of the peripheral arteries.

Using this info, one calculates the mean concentration of dye in the arterial blood by measuring the area under the extrapolated dye concentration curves.

Front 47

47. What are the lub and dub sounds associated with?

Back 47

The lub is associated with closure of the AV valves at the beginning of systole

The dub is associated with closure of the semilunar (aortic and pulmonary) valves at the end of systole.

Front 48

48. What is the cause of the first and second heart sounds?

Back 48

The cause is vibration of the taut valves immediately after closure, along with vibration of the adjacent walls of the heart and major vessels around the heart.

In the first heart sound, the vibrations travel through the adjacent tissues to the chest wall.

In the second heart sounds, the vibrations occurring in the arterial walls are then transmitted mainly along the arteries. When the vibrations of the vessels or ventricles come into contact with the chest wall, they create a sound that can be heard.

Front 49

49. Duration and pitch of each of the heart sounds?

Back 49

The first heart sound is about 0.14 sec long and has a lower frequency

The second heart sound is about 0.11 sec long and has a higher frequency.

Front 50

50. Why does the second heart sound have a higher frequency?

(2 reasons...)

Back 50

For two reasons:
1. The tautness of the semilunar valves in comparison with the much less taut A-V valves

2. The greater elastic coefficient of the taut arterial walls that provide the principal vibrating chambers for the second sound, in comparison with the much looser, less elastic ventricular chambers that provide the vibrating system for the first heart sound.

Front 51

51. What is the third heart sound?

Back 51

A weak, rumbling third heart sound is sometimes heard at the beginning of the middle third of diastole.

This sound is caused by oscillation of blood back and forth between the walls of the ventricles initiated by inrushing blood from the atria.

The freq of this sound is usually so low that the ear cannot hear it.

Front 52

52. What is the fourth heart sound?

Back 52

An atrial heart sound can sometimes be recorded by a phonocardiogram, but it can almost never be heard with a stethoscope b/c of its weakness and very low freq.

This sound occurs when the atria contract, and presumably, it is caused by the inrush of blood into the ventricles, which initiates vibrations similar to those of the third heart sound.

Front 53

53. Areas for listening to the different heart sounds

Back 53

Not directly over the valves themselves:

Aortic: 2nd intercostal space to the right of the sternal border

Pulmonary: 2nd intercostal space to the left of the sternal border

Tricuspid: Next to the sternum on the left in the 5th intercostal space

Mitral: Left sternal border in the 5th intercostal space

Front 54

54. What are rheumatic valvular lesions?

Back 54

By far the greatest number of valvular lesions results from rheumatic fever. Rheumatic fever is an autoimmune disease in which the heart valves are likely to be damaged or destroyed. It is usually initiated by streptococcal toxin.

Front 55

55. How does the streptococcal toxin initiate the rhematic valvular lesions?

Back 55

1. Strep infection caused by group A hemolytic streptococci.
2. Strep also release several different proteins against which the person's body produces antibodies.
3. The antibodies react not only with the strep protein but also with other protein tissues of the body, often causing severe immunological damage.
4. Antibodies concentrate and persist in the heart valves and grow large hemorrhagic, fibrinous, bulbous lesions.

Front 56

56. Which valves are affected in rheumatic fever?

Back 56

B/c the mitral valve receives more trauma during valvular action than any of the other valves, it is the one most seriously damage, and the aortic valve is second.

The right heart valves, tricuspid and pulmonary, are usually affected much less, probably b/c the low pressure stresses that act on these valves are slight.

Front 57

57. Scarring of the valves in rheumatic fever

Back 57

The lesion frequently occur on adjacent valve leaflets simultaneously, so that the edges of the leaflets become stuck together. Later, these lesions become scar tissue, permanently fusing portions of adjacent valve leaflets.

Also, the free edges of the leaflets, which are normally filmy and free-flapping, often become solid, scarred masses.

Front 58

58. What happens to the scarred heart valves?

Back 58

A valve in which the leaflets adhere to one another so extensively that blood cannot flow through it normally is said to be stenosed.

Conversely, when the valve edges are so destroyed by scar tissue that they cannot close as the ventricles contract, regurgitation of blood occurs.

Stenosis usually does not occur w/o some degree of regurgitation, and vice versa.

Front 59

59. What is a common finding heard in aortic stenosis?

Back 59

In aortic stenosis, a systolic murmur is heard during systole and is transmitted through the superior thoracic aorta and even into the large arteries of the neck.

Also, the sound vibrations can often be felt with the hand on the upper chest and lower neck, called a palpable "thrill"

Front 60

60. What is a common finding heard in aortic regurgitation?

Back 60

A "blowing" murmur is heard with a high pitch and a swishing quality heard maximally over the left ventricle during diastole.

This murmur results from turbulence of blood jetting backward into the blood already in the low-pressure diastolic left ventricle.

Front 61

61. What is a common finding heard in mitral regurgitation?

Back 61

A high freq blowing murmur is heard similar to that of aortic regurgitation, but it occurs during systole rather than diastole.

It is transmitted to the chest wall mainly through the left ventricle to the apex of the heart.

Front 62

62. What is a common finding heard in mitral stenosis?

Back 62

No murmur may be heard during the first third of diastole. Then, after partial filling, the ventricle has stretched enough for blood to reverberate, and a low rumbling murmur begins.

These sounds are usually weak and of very low frequency.

Front 63

63. In sum, which murmurs occur during systole, and what occur during diastole?

Back 63

Systole: Aortic stenosis and mitral regurgitation

Diastole: Aortic regurgitation and mitral stenosis

Front 64

64. In aortic stenosis and aortic regurgitation, how is the net stroke volume output of the heart affected?

Back 64

The net stroke volume output of the heart is reduced.

As a result, several important compensations take place that can ameliorate the severity of the circulatory defects.

These include:
1. Hypertrophy of the left ventricle
2. Increase in blood volume

Front 65

65. How does hypertrophy of the left ventricle compensate?

Back 65

Sometimes the left ventricular muscle mass increases 4-5x to create a force strong enough to overcome regurgitation or stenosis.

Front 66

66. In compensation, what does the increased blood volume result from?

What is the effect of an increased blood volume?

Back 66

This results from:
1. An initial slight decrease in arterial pressure
2. Peripheral circulatory reflexes that the decrease in pressure induces

These together diminish renal output of urine, causing the blood volume to increase and the mean arterial pressure to return to normal. Also, red cell mass eventually increases b/c of a slight degree of tissue hypoxia.

Front 67

67. What happens when the aortic stenosis/regurgitation progress to or beyond a critical stage?

Back 67

Beyond a critical stage in these aortic valve lesions, the left ventricle finally cannot keep up with the work demand.

As a consequence, the left ventricle dilates and CO beings to fall; blood simultaneously dams up in the left atrium and in the lungs behind the failing left ventricle.

The left atrial pressure rises progressively, and at mean left atrial pressures above 25 - 40 mm Hg, serious edema appears in the lungs.

Front 68

68. What are some consequences of mitral stenosis/regurgitation?

Back 68

Either of these conditions reduces net movement of blood from the left atrium into the left ventricle.

Can result in:
1. Pulmonary edema
2. Enlarged left atrium and atrial fibrillation
3. Compensation in early mitral valvular disease

Front 69

69. What causes the pulmonary edema in mitral valvular disease?

Back 69

The buildup of blood in the left atrium causes progressive increase in left atrial pressure, and this eventually results in development of serious pulmonary edema.

Usually, lethal edema does not occur until the mean left atrial pressure rises above 25 - 40 mm Hg, b/c the lung lymphatic vasculature enlarges manyfold and can carry fluid away from the lung tissues rapidly.

Front 70

70. Consequences of an enlarged left atrium

Back 70

The high left atrial pressure in mitral valvular disease results in left atrial hypertrophy, which increases the distance that the cardiac electrical excitatory impulse must travel in the atrial wall.

This pathway may eventually become so long that it predisposes to development of excitatory signal circus movements (can cause atrial fibrillation, especially in mitral stenosis).

Front 71

71. What is the compensation that occurs in early mitral valvular disease?

Back 71

The blood volume increases in mitral valvular disease principally b/c of diminished excretion of water and salt by the kidneys. Thsi increased blood volume increases venous return to the heart, thereby helping to overcome the effect of the cardiac debility.

Can also result in hypertrophy of the right side of the heart which compensates for its increased workload due to increases in right ventricular pressures.

Front 72

72. What can occur in patients w/aortic valvular lesions during exercise?

What about those w/mitral disease?

Back 72

Exercise can cause acute left ventricular failure followed by acute pulmonary edema.

In mitral disease, exercise can cause so much damming of blood in the lungs that serious or even lethal pulmonary edema may ensue in as little as 10 minutes.

In both conditions, the cardiac output does not increase as much as it should during exercise due to a reduced cardiac reserve.

Front 73

73. What are the three major types of congenital anomalies of the heart?

Back 73

1. Stenosis of the channel of blood flow at some point in the heart or in a closely allied major blood vessel.

2. An anomaly that allows blood to flow backward from the left side of the heart or aorta to the right side of the heart or pulmonary artery, thus failing to flow thru systemic circulation (left-to-right shunt)

3. An anomaly that allows blood to flow directly from the right side of the heart into the left side of the heart, thus failing to flow through the lungs - called a right-to-left shunt.

Front 74

74. Why does the ductus arteriosus close after birth?

Back 74

When the lungs inflate for the first time, the pulmonary arterial pressure falls. Simultaneously, the aortic pressure rises b/c of sudden cessation of blood flow from the aorta thru the placenta. Thus, the pressure in the pulmonary artery falls, while that in the aorta rises.

As a result, forward blood flow thru the ductus ceases suddenly at birth, and blood begins to flow backward thru the ductus from the aorta into the pulmonary artery.

This new state of backward blood flow causes the ductus to become occluded.

Front 75

75. Specifically, what causes the ductus arteriosus?

Back 75

It is believed to be closed b/c the oxygen concentration of the aortic blood now flowing thru it is about 2x as high as that of the blood flowing from the pulmonary artery into the ductus during fetal life.

The oxygen presumably constricts the muscle in the ductus wall.

Front 76

76. Recirculation through the lungs in PDA

Back 76

In an older child with a PDA, 1/2 to 2/3's of the aortic blood flows backward through the ductus into the pulmonary artery.

These people do not show cyanosis until later in life, when the heart fails or the lungs become congested.

Indeed, early in life, the arterial blood is often better oxygenated than normal b/c of the extra times it passes thru the lungs.

Front 77

77. What is a consequence of a PDA on cardiac and respiratory function?

Back 77

The major effects of PDA on the patient are decreased cardiac and respiratory reserve.

With even moderately strenuous exercise, the person is likely to become weak and may even faint from momentary heart failure.

The high pressures in the pulmonary vessels often lead to pulmonary congestion and pulmonary edema.

Most patients with uncorrected PDA die from heart disease between 20-40 yrs/age.

Front 78

78. What is the characteristic sound of a PDA?

Back 78

Machinery murmur that waxes and wanes with each beat of the heart

Front 79

79. What are the four conditions that occur simultaneously in Tetralogy of Fallot?

Back 79

1. Overriding aorta
2. Pulmonary artery stenosis
3. VSD
4. Right ventricular hypertrophy

Most common cause of blue baby.

Front 80

80. Dx of Tetralogy of Fallot is based on what four things?

Back 80

1. The fact that the baby is cyanotic
2. Measurement of high systolic pressure in the right ventricle
3. Characteristic changes in the radiological silhouette of the heart, showing an enlarged right ventricle
4. Angiograms showing abnormal blood flow through the interventricular septal hole and into the overriding aorta, but much less flow thru the stenosed pulmonary artery.

Front 81

81. What is one cause of congenital heart defects?

Back 81

Defects are particularly prone to develop when the expectant mother contracts German measles.

Front 82

82. What are 4 methods of oxygenating blood?

Back 82

1. Bubbling oxygen thru the blood and removing the bubbles from the blood before passing it back into the patient.
2. Dripping the blood downward over the surfaces of plastic sheets in the presence of oxygen.
3. Passing the blood over surfaces of rotating discs.
4. Passing the blood between thin membranes or through thin tubes that are permeable to oxygen and carbon dioxide.

Front 83

83. What are the three types of arteries?

Back 83

1. Large or elastic arteries
2. Medium-sized or muscular arteries
3. Small arteries and arterioles

*The relative amount and configuration of the basic constituents vary along the arterial system owing to local adaptations to mechanical or metabolic needs.

Front 84

84. What are the principal points of physiologic resistance to blood flow in the body?

Back 84

The arterioles are the principal points of physiologic resistance to blood flow.

Front 85

85. Where does vascular leakage and leukocyte exudation occur in many types of inflammation?

Back 85

In the postcapillary venules.

Front 86

86. Which are more prone to irregular dilation, compression, degeneration, and vascular invasion - arteries or veins?

Back 86

B/c of their poor support, veins are predisposed to irregular dilation, compression, degeneration, and vascular invasion.

Front 87

87. What are 8 functions of endothelial cells?

Back 87

1. Maintenance of permeability barrier
2. Elaboration of anticoagulant, antithrombotic, fibrinolytic regulators
3. Elaboration of prothrombotic molecules
4. ECM production (collagen, proteoglycans)
5. Modulation of blood flow and vascular reactivity
6. Regulation of inflammation and immunity
7. Regulation of cell growth
8. Oxidation of LDL

Front 88

88. What are the three physiologic responses to vascular injury?

Back 88

1. Smooth muscle cells migrate from the media to the intima
2. Smooth muscle cell mitosis
3. Synthesize and deposit ECM

Front 89

89. What are arteriovenous fistulas?

Back 89

These are rare, usually small, abnormal communications between arteries and veins. They arise as developmental defects, but can also be produced from rupture of an arterial aneurysm into the adjacent vein, from penetrating injuries that pierce the walls of artery and vein, or from inflammatory necrosis of adjacent vessels.

These may be of clinical significance b/c they short-circuit blood from the arterial to the venous side, thereby causing the heart to pump additional volume; sometimes high-output cardiac failure ensues.

Front 90

90. What is atherosclerosis?

Back 90

Atherosclerosis is a slowly progressive disease of large to medium sized muscular and large elastic arteries.

It is characterized by elevated intimal-based fibrofatty plaques composed of lipids, proliferating smooth muscles cells, and increased ECM.

Lesions are initially focal, with patchy vessel involvement both circumferentially and longitudinally.

Front 91

92. What are the common locations for atherosclerosis to occur (in decreasing order)?

Back 91

In decreasing order:

1. Abdominal aorta
2. Coronary arteries
3. Popliteal arteries
4. Descending thoracic aorta
5. Internal carotid arteries
6. Circle of Willis

Front 92

92. What is the morphology of an atheromatous plaque?

Back 92

The characteristic atheromatous plaque is a raised white-yellow intimal based lesion, protruding into the vessel lumen.

Histologically, plaques are composed of superficial fibrous caps containing SMCs, leukocytes, and dense connective tissue ECM overlying necrotic cores, containing dead cells, lipid, cholesterol clefts, lipid-laden foam cells, and plasma proteins; small blood vessels proliferate at the intimal medial interface.

Front 93

93. What are the two common variants of atheromatous plaques?

Back 93

1. Fatty streaks
2. Complicated plaques

Front 94

94. What are fatty streaks?

Back 94

Fatty streaks are early lesions composed of intimal collections of lipid-laden macrophages and SMCs in patients as young as 1 y/o. They start as multiple yellow, flat spots less than 1mm in diameter that coalesce into elongated streaks, 1 cm or longer. They contain T lymphocytes and extracellular lipid in smaller amts than in plaques.

A causal relationship between fatty streaks and atheromatous plaques is suspected but remains unproved.

Front 95

95. What are complicated plaques?

Back 95

Complicated plaques are calcified, hemorrhagic, fissured, or ulcerated atheromas, predisposing to local thrombosis, medial thinning, cholesterol microemboli and aneurysmal dilation.

Front 96

96. What are the three principal components of atherosclerotic plaques?

Back 96

1. Cells, including SMCs, macrophages, and other leukocytes

2. ECM, including collagen, elastic fibers, and proteoglycans

3. Intracellular and extracellular lipid

Front 97

97. What are the major consequences of atherosclerotic disease?

Back 97

Most often involves the arteries supplying the heart, brain, kidneys, and lower extremities.

1. MI
2. Cerebral infarction
3. Aortic aneurysms
4. Peripheral vascular disease (gangrene of leg)
5. Sudden cardiac death
6. Chronic, ischemic heart disease
7. Thrombosis

Front 98

98. What are the four pathological changes that have clinical significance in atherosclerosis?

Back 98

1. Focal rupture, ulceration, or erosion of the luminal surface of the plaque may result in thrombus formation

2. Hemorrhage into a plaque, especially in the coronary arteries, may be initiated by rupture of the fibrous cap.

3. Superimposed thrombosis, which may partially or completely occlude the lumen.

4. Aneurysmal dilation may result from ATH-induced atrophy of the media, with loss of elastic tissue causing weakness and potential rupture.

Front 99

99. What are some other factors that can lead to atherosclerosis besides the obvious?

Back 99

1. Homocystinuria
2. Lipoprotein A
3. Type A personality

Front 100

100. What are the non-modifiable risk factors for atherosclerosis?

Back 100

1. Increasing age
2. Male gender
3. Family history
4. Genetic abnormalities
5. Obesity
6. Physical inactivity
7. Stress
8. Postmenopausal estrogen deficiency
9. High carbohydrate intake

Front 101

101. What are the potentially controllable risk factors for atherosclerosis?

Back 101

1. Hyperlipidemia
2. Hypertension
3. Cigarette smoking
4. Diabetes
5. EtOH
6. LipoproteinA
7. Hardened (trans) unsaturated fat intake
8. Chlamydia pneumoniae

Front 102

102. What is the pathogenesis of atherosclerosis?

Back 102

The contemporary view is the response to injury hypothesis, which considered atherosclerosis to be a chronic inflammatory response of the arterial wall initiated by injury to the endothelium.

Moreover, lesion progression is sustained by interaction between modified lipoprotein, monocyte-derived macrophages, T lymphocytes, and the normal cellular constituents of the arterial wall.

Front 103

103. What are the eight factors that are central to the contemporary view of atherosclerosis?

Back 103

1. Chronic endothelial injury
2. Accumulation of lipoproteins, mainly LDL, with its high cholesterol content, in the vessel wall
3. Modification of lesional lipoproteins by oxidation
4. Adhesion of blood monocytes to the endothelium, followed by the migration and transformation into macrophages and foam cells
5. Adhesion of platelets
6. Release of factors from activated platelets, macrophages, or vascular cells that cause migration of SMCs from media into the intima
7. Proliferation of SMCs in the intima, and elaboration of ECM, leading to accumulation of collagen and proteoglycans
8. Enhanced accumulation of lipids both within cells and extracellularly

Front 104

104. What is the cornerstone of the response to injury hypothesis?

Back 104

Chronic or repetitive endothelial injury is the cornerstone of the response to injury hypothesis.

Front 105

105. What are the two most important determinants of endothelial alterations?

Back 105

1. Hemodynamic disturbances that accompany normal circulatory function

2. Adverse effects of hypercholesterolemia

Front 106

106. What do macrophages produce that increase the adhesion of leukocytes?

Back 106

Macrophages produce IL-1 and TNF, which increase adhesion of leukocytes.

Several chemokines generated by macrophages, including monocyte chemotactic protein-1, may recruit more leukocytes into the plaque.

Front 107

107. What do T lymphocytes encounter that stimulate macrophages as well as vascular endothelial cells and SMCs?

Back 107

They encounter IFN-γ and lymphotoxin, which in turn stimulate macrophages as well as vascular endothelial cells and SMCs.

Front 108

108. What three things are implicated in hypercholesterolemia in the genesis of atherosclerosis?

Back 108

1. The major lipids in atheromatous plaques are plasma-derived cholesterol and cholesterol esters.

2. Oxidized LDL is observed in macrophages in arteries at sites of fatty streaks. Antioxidant treatment protects against the development of atherosclerosis in hypercholesterolemic experimental animals.

3. Genetic defects in lipoprotein metabolism causing hyperlipoproteinemia are associated with accelerated atherosclerosis

Front 109

109. What are the three mechanisms by which hyperlipidemia contributes to atherogenesis?

Back 109

1. Chronic hyperlipidemia, particularly hypercholesterolemia, may directly impair EC function through increased production of oxygen free radicals that deactivate NO, the major endothelial relaxing factor.

2. With chronic hyperlipidemia, lipoproteins accumulate within the intima at sites of increased endothelial permeability.

3. Chemical change of lipid induced by free radicals generated in macrophages or ECs in the arterial wall yields oxidized LDL.

Front 110

110. What are four properties of oxidized LDLs?

Back 110

1. Oxidized LDL is ingested by macrophages through the scavenger receptor, distinct from the LDL receptor, thus forming foam cells.
2. Increases monocyte accumulation in lesions
3. Stimulates release of growth factors and cytokines
4. Is cytotoxic to ECs and SMCs

Front 111

111. What is the role of SMCs in the formation of atherosclerosis?

Back 111

SMCs migrate from the media to the intima, where they proliferate and deposit ECM components, converting a fatty streak into a mature fibrofatty atheroma, and contribute to the progressive growth of atherosclerotic lesions.

With progression, the atheroma is modified by SMC-synthesized collagen and proteoglycans.

Front 112

112. What is oligoclonality of atherogenic lesions?

Back 112

The monoclonal hypothesis of atherogenesis was based on observation that some human plaques are monoclonal or at most oligoclonal.

A recent study showed that clonal patches exist and are often greater than 4 mm in size in not only atherosclerotic but also normal arteries, consistent with the possibility that atherosclerotic plaques could arise in a pre-existing clonal patch.

Front 113

113. What two types of infections can contribute to atherosclerosis?

Back 113

Chlamydia pneumoniae and cytomegalovirus.

Evidence for C. pneumoniae is strongest, which includes direct detection of bacterial components in atherosclerotic lesions.

In addition, infectious organisms might potentiate the complications of existing lesions.

Front 114

114. Summary of the six mechanisms that contribute to plaque formation and progression

Back 114

1. Endothelial dysfunction
2. Monocyte adhesion and infiltration
3. Lipid accumulation and oxidation
4. SMC proliferation
5. ECM deposition
6. Thrombosis

Front 115

115. Clinical features of atherosclerosis can result from what four mechanisms?

Back 115

1. Insidious narrowing of vascular lumens
2. Plaque rupture or superficial erosion followed by superimposed thrombus causing sudden luminal occlusion
3. Vessel wall weakening followed by aneurysm formation and possible rupture.
4. Providing a source of thromboemboli

Front 116

116. What are the clinical features of atherosclerosis?

Back 116

Approximately 1/3 of all deaths in the US result from atherosclerosis, which is significant in causing MI, or sudden cardiac death, strokes, aneurysm rupture, mesenteric occlusion, and extremity gangrene.

Front 117

117. What is hypertensive vascular disease?

Back 117

Hypertension is the single most important risk factor in both coronary heart disease and strokes and can also directly cause congestive heart failure, renal failure, and aortic dissection.

Front 118

118. What causes 95% of the hypertension in most patients?

Back 118

In about 90% of cases hypertension has no known cause (primary or essential hypertension).

The remainder are mostly secondary to renal disease or (less often) to renal artery stenosis (renovascular hypertension), endocrine abnormalities, vascular malformations, or neurogenic disorders.

Front 119

119. What causes the bottom 5% of the hypertension in most patients?

Back 119

A small percentage of hypertensive persons show a rapidly rising blood pressure that if untreated, leads to death within a year or two.

This is called accelerated or malignant hypertension (systolic over 200 and diastolic over 120.

It may develop in previously normotensive persons but more often is superimposed on pre-existing benign hypertension, either essential or secondary.

Front 120

120. What are the 3 characteristics of malignant hypertension?

Back 120

1. Severe hypertension (systolic over 200 and diastolic over 120)
2. Renal failure
3. Retinal hemorrhages and exudates with or without papilledema

Front 121

121. When does arterial hypertension occur?

Back 121

Arterial hypertension occurs when the relationship between cardiac output and total peripheral resistance is altered.

Front 122

122. In what two ways does the renal artery stenosis cause increased BP?

Back 122

1. The decreased GFR induces renin secretion, initiating angiotensin II mediate vasoconstriction and increased peripheral resistance.

2. The resultant increases sodium reabsorption and therefore blood volume through the aldosterone mechanism.

Front 123

123. What determines BP?

Back 123

Blood pressure is proportional to cardiac output and peripheral vascular resistance.

BP = CO x TPR

The BP level is a complex trait that is determined by the interaction of multiple genetic, environmental and demographic factors that influence cardiac output and vascular resistance

Front 124

124. What are the four main things that regulate BP?

Back 124

1. Sodium load, mineracorticoids, and natriuretic factors

2. Vasoconstriction increases vascular resistance:
-includes angiotensin II, catecholamines, thromboxane, leukotrienes, and endothelin

3. Vasodilation decreases vascular resistance
-includes kinins, prostaglandins, nitric oxide, and adenosine

4. Regional autoregulation, wherein increased blood flow leads to vasocontriction (and vice versa).

Front 125

125. How do the kidneys regulate blood pressure?

Back 125

Through the renin-angiotensin system - angiotensin II raises BP by increasing both peripheral resistance and blood volume

When the blood volume is reduced, the GFR falls, leading to increased reabsorption of Na by proximal tubules and thereby conserving sodium and expanding blood volume

The kidneys respond to natriuretic factors by inhibiting sodium reabsorption is distal tubules and thereby cause sodium excretion and diuresis.

When renal excretory function is impaired, increased arterial pressure is a compensatory mechanism that helps restore fluid and electrolyte imbalance.

Front 126

126. What are the mechanisms of essential hypertension?

What are the two systems that can have abnormalities in essential hypertension?

Back 126

Essential hypertension is caused by increased blood volume (due to reduced renal sodium excretion) or increased peripheral resistance (due to increased release of vasocontrictor agents), or both.

Two systems that can have abnormalities in essential hypertension:
1. The renin-angiotensin system
2. Sodium homeostasis

Front 127

127. What genetic disorders cause hypertension?

For instance, what is Liddle syndrome?

Back 127

1. Gene defects in enzymes involved in aldosterone metabolism (e.g. aldosterone synthase, 11β-hydroxylase, 17α-hydroxylase). These lead to an adaptive increase in secretion of aldosterone, increased salt and water resorption, plasma volume expansion, and hypertension.

2. Mutations in proteins that affect sodium reabsorption. For example, the moderately severe form of salt-sensitive hypertension, called Liddle syndrome, is caused by mutations in an ENaC protein that lead to increased distal tubular reabsorption of sodium induced by aldosterone.

Front 128

128. What is the vascular pathology in hypertension?

Back 128

Hypertension accelerates atherogenesis and causes structural changes that potentiate both aortic dissection and cerebrovascular hemorrhage.

In addition, hypertension is associated with arteriolosclerosis, primarily affecting arterioles and small arteries, particularly in the kidney.

Front 129

129. What are the two types of arteriosclerosis?

Back 129

1. Hyaline arteriolosclerosis
2. Hyperplastic arteriolosclerosis

Front 130

130. What is hyaline arteriolosclerosis?

Back 130

Hyaline arteriolosclerosis is a major morphologic characteristic of benign nephrosclerosis.

It typically occurs in elder people, particularly those with mild hypertension and mild diabetes. The lesion probably reflects EC injury, with subsequent plasma leakage into the arteriolar walls and ECM synthesis by SMCs.

Microscopically, there is diffuse, pink, hyaline arteriolar thickening.

Front 131

131. What is hyperplastic arteriolosclerosis?

Back 131

Hyperplastic arteriolosclerosis is characteristic of malignant hypertension.

There is concentric laminated (onion-skin) arteriolar thickening with reduplicated basement membrane and SMC proliferation, frequently associated with fibrin deposition and acute necrosis of the vessel walls, so-called necrotizing arteriololitis, particularly in the kidney.

Front 132

132. What is an aneurysm?

What is a true aneurysm vs. a false aneurysm?

Back 132

An aneurysm is a localized abnormal dilation of blood vessel or the wall of the heart.

When an aneurysm is bounded by arterial wall components or the attenuated wall of the heart, it is called a true aneurysm.

In contrast, a false aneurysm is a breach in the vascular wall leading to an extravascular hematoma that freely communicates w/the intravascular space ("pulsating hematoma").

Front 133

133. What are examples of true aneurysms?

False aneurysms?

Back 133

Atherosclerotic, syphilitic, and congenital vascular aneurysms and the left ventricular aneurysm that can follow a MI are of the true aneurysm type.

The most common false aneurysm is a post MI rupture that has been contained by a pericardial adhesion, or a leak at the junction (anastomosis) of a vascular graft w/a natural artery.

*Both true and false aneurysms can rupture.

Front 134

134. What are the two most important causes of aortic aneurysms?

Back 134

1. Atherosclerosis
2. Cystic medial degeneration of the arterial media

Front 135

135. What is a mycotic aneurysm?

What are the three ways in which they may originate?

Back 135

Infection of a major artery that weakens its wall gives rise to mycotic aneurysm.

They may originate either (1) from embolization and arrest of a septic embolus at some point w/in a vessel, usually as a complication of infective endocarditis; (2) as an extension of an adjacent suppurative process; or (3) by circulating organisms directly infecting the arterial wall.

Front 136

136. What are saccular aneurysms?

What are fusiform aneurysms?

Back 136

Saccular aneurysms are essentially spherical and vary in size from 5-20 cm in diameter, often partially or completely filled by thrombus.

Alternatively, aneurysms may be fusiform (involving a long segment). Fusiform aneurysms vary in diameter (up to 20 cm) and in length; many involve the entire ascending and transverse portions of the aortic arch, whereas others may involve large segments of the abdominal aorta or even the iliacs.

Front 137

137. Where do atherosclerotic aneurysms occur most frequently?

Back 137

Atherosclerotic aneurysms occur most freq in the abdominal aorta (AAA), but the common iliac arteries, the arch, and descending parts of the thoracic aorta can be involved.

Front 138

138. What is the morphology of AAA?

Back 138

Usually positioned below the renal arteries and above the bifurcation of the aorta, AAAs are saccular or fusiform, sometimes up to 15 cm in greatest diameter and of various length.

The aneurysm and the nearby aorta often contain atheromatous ulcers covered by granular mural thrombi, prime sites for the formation of atheroemboli that may lodge in the vessels of the kidneys or lower extremities. Additionally, a thrombus freq fill at least part of the dilated segment.

Not infrequently, AAAs are accompanied by smaller fusiform or saccular dilations of the iliac arteries.

Front 139

139. What is the inflammatory AAA variant?

Back 139

Inflammatory AAAs are characterized by dense periaortic fibrosis containing an abundant, inflammatory reaction rich in lymphocytes and plasma cells w/many macrophages and often giant cells.

Their cause is uncertain.

Front 140

140. What is the mycotic AAA variant?

Back 140

Mycotic AAAs are atherosclerotic AAAs that have become infected by lodgment of circulating organisms in the wall, particularly in bactermeia from a primary Salmonella gastroenteritis.

In such cases, suppuration can further destroy the media, potentiating rapid dilation and rupture.

Front 141

141. What is the pathogenesis of AAAs?

Back 141

Atherosclerosis is a major cause of AAAs, but other factors may contribute. They rarely develop before age 50 and are more common in men. There is a genetic susceptibility to AAAs in that altered collagen or its remodeling could provide a susceptible substrate on which atherosclerosis or hypertension could act to weaken the aortic wall.

In this regard, the MMPs have been implicated in the development of AAAs thru increased proteolysis of ECM proteins. MMPs are expressed in aortic aneurysms at elevated levels compared w/normal vessel wall. Also, a decreased level of tissue inhibitor of MMPs has been reported in AAA.

Front 142

142. What is the clinical course of AAAs?

Back 142

Risk of rupture increases w/the max diameter of the AAA; minimal risk if smaller than 5 cm but a risk of 5-10% annually when greater than 5 cm.

Operative mortality rate is 5% of unruptured aneurysm but more than 50% after rupture.

B/c aortic atherosclerosis is usually accompanied by severe coronary atherosclerosis, patients w/AAA have a high incidence of ischemic heart disease.

Front 143

143. What are syphilitic (leutic) aneurysms?

What do most patients with this die from?

Back 143

The obliterative endarteritis characteristic of the tertiary stage of syphilis (lues) shows a predilection for small vessels, w/complications especially in the aorta and nervous system.

Syphilitic involvement of the vasa vasorum of the thoracic aorta van lead to aneurysmal dilation that can include the aortic annulus.

*Most patients w/syphilitic aneurysms die of heart failure induced by aortic valvular incompetence.

Front 144

144. What is the morphology of syphilitic aneurysms?

Back 144

Inflammatory involvement begins in the aortic adventitia, particularly involving the vasa vasorum, inducing obliterative endartertis rimmed by an infiltrate of lymphocytes and plasma cells (sphilitic aortitis). The narrowing of the lumina causes ischemic injury of the aortic media.

W/destruction of the media, the aorta loses its elastic recoil and may become dilated, producing a syphilitic aneurysm. Contraction of fibrous scars may lead to wrinkling of intervening segments of aortic intima, called "tree-barking".

*Luetic involvement of the aorta favors the development of superimposed atheromatosis of the aortic root, which can envelop and occlude the coronary ostia.

Front 145

145. What is a complication of leutic aortitis?

What is cor bovinum?

Back 145

Luetic aortitis may also cause aortic valve ring dilation, resulting in valvular insufficiency thru circumferential stretching of the valve cusps, widening of the commissures btwn the cusps, and turbulence-induced thickening and rolling of the free margins.

Owing to aortic insufficiency, the left ventricular wall can undergo massive volume overload hypertrophy and be referred to as "cor bovinum" (cow's heart).

Front 146

146. What are the 7 complications of thoracic aneurysms?

Back 146

1. Encroachment on mediastinal structures
2. Respiratory difficulties due to encroachment on the lungs and airways
3. Difficulty in swallowing due to compression of the esophagus
4. Persistent cough due to irritation of or pressure on the recurrent laryngeal nerves
5. Pain caused by erosion of bone
6. Cardiac disease as the aortic aneurysm leads to aortic valve dilation and insufficiency
7. Rupture

Front 147

147. What is an aortic dissection (dissecting hematoma)?

Back 147

Aortic dissection is a catastrophic illness characterized by dissection of blood between and along the laminar planes of the media, with the formation of a blood-filled channel, within the aortic wall, which often ruptures outward, causing massive hemorrhage.

*May or may not be associated w/marked dilation of the aorta.

Front 148

148. What is the prevalence of aortic dissection?

Back 148

Aortic dissection occurs in two groups of people:

1. Men between the ages of 40-60 with antecedent hypertension (90%)
2. Usually younger group that has a systemic or localized abnormality of connective tissue defects that affects the aorta (e.g., Marfan syndrome)

Front 149

149. What is the morphology of aortic dissection?

1/2

Back 149

In spontaneous dissection, an intimal tear that is presumably the origin extends into but not thru the media of the ascending aorta, usually w/in 10 cm of the aortic valve. These tears are transverse or oblique, 1-5 cm in length and have sharp, jagged edges.

The dissection can extend proximally toward the heart as well as distally all the way into the iliac and femoral arteries.

The dissecting hematoma spreads characteristically along the laminar planes of the aorta, usually between the middle and outer thirds.

Front 150

150. What is the morphology of aortic dissection?

2/2

Back 150

In some instances, the blood reruptures into the lumen of the aorta, producing a second or distal intimal tear and a new vascular channel within the media of the aortic wall (to produce a "double-barreled aorta" with a false channel).

In the course of time, false channels may become endothelialized ("chronic dissection")

Front 151

151. What is the most frequent preexisting histologically detectable lesion in aortic dissection?

Back 151

Medial degeneration (AKA cystic medial degeneration).

Medial degeneration is characterized by elastic tissue fragmentation and separation of the elastic and fibromuscular elements of the tunica media by small cleftlike spaces where the normal elastic tissue is lost; these areas are filled with amorphous ECM of connective tissue and resembles cysts.

*Medial degeneration of the aorta frequently accompanies Marfan syndrome.

Front 152

152. What is the pathogenesis of aortic dissection?

Back 152

Hypertension is clearly the major risk factor. Some dissections are related to inherited connective tissue disorders, most prominently Marfan syndrome.

Regardless of etiology, the trigger for the intimal tear and intramural aortic hemorrhage is unknown in most cases. Once the tear has occurred, increases systemic BP fosters progression of the medial hematoma.

Front 153

153. What is the clinical course of aortic dissections?

What is the most common cause of death?

Back 153

The classic symptoms are the sudden onset of excruciating pain, usually beginning in the anterior chest, radiating to the back, and moving downward as the dissection progresses. This pain can be readily confused with that of an acute MI.

The most common cause of death is rupture of the dissection outward into any of the three body cavities. This can then lead to cardiac tamponade, aortic insufficiency, and MI.

The prognosis has markedly improved; surgical repair and early treatment w/antihypertensive meds permit salvage of 65-75% of pts w/dissections.

Front 154

154. What determines the clinical course of aortic dissection?

Back 154

The risk and nature of complications depend on the level of the aorta affected, w/the most serious complications occurring from the aortic valve to the arch.

There are two types of aortic dissections:
1. Type A - the more common (and serious or potentially damaging) proximal lesions, involving either the ascending portion only or both the ascending and the descending aorta.
2. Type B - distal lesions not involving the ascending part and usually beginning distal to the subclavian artery.

Front 155

155. What is vasculitis?

Back 155

Inflammation of the walls of vessels, called vasculitis, is encountered in diverse clinical settings.

Clinical manifestations often include constitutional signs and symptoms such as fever, myalgias, arthralgias, and malaise, or local manifestations of downstream tissue ischemia.

Front 156

156. What are the two most common mechanisms of vasculitis?

Back 156

1. Direct invasion of vascular walls by infectious pathogens
2. Immune mediated mechanisms

Front 157

157. What are the three main immunologic mechanisms that initiate noninfectious vasculitis?

Back 157

1. Immune complex deposition
2. Antineutrophil cytoplasma antibodies
3. Anti-endothelial cell antibodies

Front 158

158. What is the evidence for immune complexes in noninfectious vasculitis?

Back 158

1. The vascular lesions resemble those found in the Arthus phenomenon and serum sickness. Immune reactants and complement can be detected in the serum or vessels of patients with vasculitis.
2. Hypersensitivity to drugs causes approx 10% of vasculitic skin lesions, largely thru vascular deposits of immune complexes.
3. In vasculitis associated w/viral infection, immune complexes can be found in the serum and in the vascular lesions of some pts, particularly in the cases of polyarteritis nodosa (for example, HBsAg-anti-HbsAg in hepatitis induced vasculitis).

Front 159

159. What are antineutrophil cytoplasmic antibodies (ANCAs)?

Back 159

ANCA are a heterogeneous group of autoantibodies directed against enzymes mainly found within the azurophil or primary granules in neutrophils, in the lysosome of monocytes, and in ECs.

Two main patterns are recognized, those in the cytoplasm (c-ANCA with the most common target proteinase-3 - PR3) and those in the perinucleus (p-ANCA) and is usually specific for myeloperoxidase - MPO.

Front 160

160. In what disorders is c-ANCA typically found?

p-ANCA?

Back 160

c-ANCA is typically found in Wegener granulomatosis and p-ANCA is found in most cases of microscopic polyangiitis and Churg-Strause syndrome.

Front 161

161. How are ANCAs useful?

Back 161

They serve as useful quantitative diagnostic markers for ANA-associated vasculitis, and their levels may reflect the degree of inflammatory activity.

ANCAs rise in episodes of recurrence, and thus are useful in management. In addition, the close association btwn ANCA titers and disease activity suggests they may be important in the pathogenesis of this disease.

Front 162

162. What is a hypothesis for the causative role of ANCAs in vasculitis?

Back 162

1. An underlying disorder (infection) elicits pro-inflammatory cytokines such as TNF and GMCSF, and endotoxin, which together cause neutrophils and other inflammatory cells to express PR3 and MPO on their surfaces.
2. These stimulate the formation of ANCAs
3. ANCAs react w/circulating cytokine primed neutrophils and cause them to degranulate
4. PMNs activated by ANCA cause endothelial cell toxicity and other direct tissue injury

Front 163

163. What are anti-endothelial cell antibodies?

Back 163

Antibodies, to ECs, perhaps induced by defects in immune regulation, may predispose to certain vasculitides, such as those associated w/SLE and Kawasaki disease.

Front 164

164. What is giant cell (temporal) arteritis?

Back 164

Giant cell arteritis, the most common form of systemic vasculittis in adults, is an acute and chronic, often granulomatous, inflammation of arteries of large to small size.

It principally affects the arteries in the head, especially the temporal, vertebral, and ophthalmic arteries. Ophthalmic arterial involvement may lead to permanent blindness. Therefore, visual loss caused by giant cell arteritis is a medical emergency.

Front 165

165. What is the morphology of giant cell (temporal) arteritis?

Back 165

Characteristically, segments of affected arteries develop nodular thickenings w/reduction of the lumen and may become thrombosed. In the more common variant there is granulomatous inflammation of the inner half of the media centered on the internal elastic membrane marked by a mononuclear infiltrate, multinucleate giant cells, and fragmentation of the internal elastic lamina.

The healed stage reveals collagenous thickening of the vessel wall; organization of the luminal thrombus sometimes transforms the artery into a fibrous cord.

Front 166

166. What is the pathogenesis of giant cell arteritis?

Back 166

The granulomatous nature of the inflammation, association w/certain HLA-DR haplotypes, and the response to corticosteroid therapy are consistent w/T-cell mediated and antigen-driven injury.

Striking features of the disorder are the rarity of the disease in persons younger than 50, the predilection for the superficial temporal arteries, and the high incidence in populations of Nordic origins.

Front 167

167. What are the clinical features of giant cell arteritis?

Back 167

Rare before age 50. Temporal arteritis typically presents w/headache and facial pain; 50% of patients have systemic symptoms, including a flu-like syndrome w/myalgias, arthralgias, and fever, called polymyalgia rheumatica.

It may cause visual disturbances (diplopia) and even blindness (an acute emergency). It responds well to corticosteroids.

Front 168

168. What is Takayasu arteritis?

Back 168

This granulomatous vasculitis of mediuma nd larger arteries is characterized principally by ocular disturbances and marked weakening of the pulses in the upper extremities (pulseless disease)

The pathologic findings that account for the clinical picture are vasculitis and subsequent fibrous thickening of the aorta, particularly the aortic arch and its branches, w/narrowing or virtual obliteration of the origins or more distant portions.

Front 169

169. What is the prevalence of Takayasu arteritis?

Back 169

The illness is seen predominantly in females younger than 40. The cause and pathogenesis are unknown, although autoimmune mechanisms are suspected.

A high frequency of the HLA-A24-B52-DR2 has been found in Japanese patients but not in other populations.

Front 170

170. What is the morphology of Takayasu arteritis?

1/2

Back 170

Takayasu arteritis classically involves the aortic arch, but in 1/3 of cases it also affects the remainder of the aorta and its branches. In 1/2 the cases it affects the pulmonary arteries.

*The gross morphologic changes include irregular thickening of the aortic or branch vessel wall w/intimal wrinkling.

Histologically, the changes range from an adventitial mononuclear infiltrate w/perivascular cuffing of the vasa vasorum to intense mononuclear inflammation of the media.

Front 171

171. What is the morphology of Takayasu arteritis?

2/2

Back 171

Granulomatous inflammation, replete w/giant cells and patchy necrosis of the media in some cases may be indistinguishable from those in giant cell arteritis.

Thus, distinctions among active giant cell lesions of the aorta are based largely on the age of the patient, and most giant cell lesions of the aorta in young patients are designated Takayasu arteritis.

Front 172

172. What are the clinical features of Takayasu arteritis?

Back 172

The salient clinical features include markedly lower BP and weaker pulses in the upper extremities with coldness or numbness of the fingers; ocular disturbances, including visual defects, retinal hemorrhages and total blindness; hypertension, and neurological deficits.

Involvement of the more distal aorta may lead to claudication of the legs; that of pulmonary arteries may lead to pulmonary hypertension.

Front 173

173. What is polyarteritis nodosa (PAN)?

Back 173

PAN is a systemic vasculitits of small or medium-sized muscular arteries (but not arterioles, capillaries, or venules), typically involving renal and visceral vessels but sparing the pulmonary circulation. Clinical manifestations result from ischemia and infarction of affected tissues and organs.

Front 174

174. What is the morphology of PAN?

Back 174

Classic PAN occurs as segmental transmural necrotizing inflammation of arteries of medium to small size, in any organ w/the possible exception of the lung, and most freq kidneys, heart, liver, and GI tract. Segmental erosion w/weakening of the arterial wall due to the inflammatory process may cause aneurysmal dilation or localized rupture. Impairment of perfusion, causing ulcerations, infarcts, ischemic atrophy, or hemorrhages in the area supplied by these vessels may provide the first clue to the existence of the underlying disorder.

Front 175

175. What are the histologic characteristics of PAN?

Back 175

The histologic picture during the acute phase is characterized by transmural inflammation of the arterial wall w/neutrophils, eosinophils, and mononuclear cells, freq accompanied by fibrinous necrosis. The lumen may become thrombosed.

Later, the acute inflammatory infiltrate infiltrate disappears and is replaced by fibrous thickening of the vessel wall that may extend into the adventitia. Firm nodularity sometimes marks the lesions.

Particularly characteristic of PAN is that all stages of activity may coexist in different vessels or even within the same vessel.

Front 176

176. What is the clinical course of PAN?

Back 176

PAN is largely a disease of young adults, w/protean and nonospecific clinical presentation related to whatever tissue is involved (e.g., hematuria, albuminuria, and hypertension [kidneys]; abdominal pain and melena [GI tract]; diffuse myalgias; and peripheral neuritis.

The most common systemic manifestations include fever, malaise, and weight loss.

PAN may be associated w/HBV antigenemia, and deposited immune complexes may play a role in pathogenesis. Untreated, the disease is generally fatal, but a 90% remission rate is achieved w/immunosuppressive therapy.

Front 177

177. What is Kawasaki disease (mucocutaneous lymph node syndrome)?

Back 177

Kawasaki disease is an arteritis that often involves the coronary arteries, usually in young children and infants (80% of cases are <4 y/o), and is the leading cause of acquired heart disease in children in the US and Japan.

It is associated w/the mucocutaneous lymph node syndrome, an acute but usually self-limited illness manifested by fever, conjunctival and oral erythema and erosion, edema of the hands and feet, erythema of the palms and soles, a skin rash often w/desquamation, and enlargement of the cervical lymph nodes.

Front 178

178. What is the pathogenesis of Kawasaki disease?

Back 178

The cause is uncertain, but there is evidence that the vasculitis results from an immune reaction characterized by T-cell and macrophage activation to an unknown antigen, secretion of cytokines, polyclonal B-cell hyperactivity, and the formation of autoantibodies to endothelial cells and SMC, leading to acute vasculitis.

Front 179

179. What is the morphology of Kawasaki disease?

Back 179

The vasculitis is PAN like, with necrosis and pronounced inflammation affecting the entire thickenss of the vessel wall, but fibrinoid necrosis is usually less prominent in Kawasaki disease.

Although the acute vasculitis subsides spontaneously or in response to treatment, it can be complicated by aneurysm formation, thrombosis, and/or MI. As w/other causes of arteritis, healed lesions may cause obstructive intimal thickening.

Front 180

180. What is the clinical course of Kawasaki disease?

Back 180

Approx 20% of pts develop cardiovascular sequelae, ranging in severity from asymptomatic vasculitis of the coronary arteries, coronary artery ectasia, or aneurysm with rupture or thrombosis, MI, or sudden death.

Acute fatalities occur in approx 1% of pts. Pathologic changes outside the cardiovascular system are rarely significant.

The use of aspirin and IV IgG has had a significant effect on lower the rate of coronary artery aneurysms and death from the disease.

Front 181

181. What is microscopic polyangiitis?

Back 181

This type of necrotizing vaculitis generally affects arterioles, capillaries, and venules - vessels smaller than those involved in PAN.

In contrast to PAN, all lesions tend to be of the same age. It typically presents as "palpable purpura" involving the skin, or invovlement of the mucous membranes, lungs, brain, heart, GI tract, kidneys, and muscle. Skin biopsy is often diagnostic.

In contrast to PAN, necrotizing GN and pulmonary capiillaritis are particularly common.

Front 182

182. What are the major clinical features of microscopic polyangiitis?

Back 182

The major clinical features are hemoptysis, arthralgia, abdominal pain, hematuria, proteinuria, hemorrhage, and muscle pain or weakness. In many cases, an immunologic reaction to an antigen such as drugs (i.e. penicillin), microorganisms (streptococci), heterologous proteins, and tumor antigens are the precipitating cause.

*in 70% of pts, p-ANCAs are present.

Front 183

183. What is the morphology of microscopic polyangiitis?

Back 183

The lesions of microscopic polyangiitis are often histologically similar to those of PAN. In contrast to PAN, muscular and large arteries are usually spared; thus, macroscopic infarcts similar to those seen in PAN are uncommon.

Granulomatous inflammation is absent.

Histologically, segmental fibrinoid necrosis of the media may be present, but some lesions have changes limited to infiltration w/neutrophils, which become fragmented as they follow the vessel wall (leukocytoclasia).

The term leukocytoclastic angiitis (LCA) is given to such lesions, most commonly found in postcapillary venules.

Ig's and complement are often present in the vascular lesions of the skin; they is a paucity of Ig demonstrable via pauci-immune injury.

Front 184

184. What is the clinical course of microscopic polyangiitis?

Back 184

W/the exception of those who develop widespread renal or brain involvement, most pts respond well simply to removal of the offending agent.

Disseminated vascular lesions of hypersensitivity angiitis may also appear in Henoch-Schonlein purpura, essential mixed cryoglobulinemia, vasculitis associated w/some of the CT disorder, and vasculitis associated w/malignancy.

Front 185

185. What is allergic granulomatosis and angiitis (Churg-Strauss syndrome)?

Back 185

In Churg-Strauss syndrome, vascular lesions may be histologically similar to those of classic PAN or microscopic polyangiitis, but they characteristically have necrotizing vasculitis accompanied by granulomas w/eosinophilic necrosis. p-ANCAs are present in 1/2 of pts.

Coronary arteritis and myocarditis are the principal causes of morbidity and mortality.

Front 186

186. What is the pathogenesis of Churg-Strauss syndrome?

Back 186

There is a strong association w/allergic rhinitis, bronchial asthma, and eosinophilia.

The disorder is thought to result from hyperresponsiveness to an allergic stimulus; in asthmatics, cysteinyl leukotriene receptor type 1 antagonists are reported to trigger it.

Front 187

187. What is Wegener granulomatosis?

Back 187

Wegener granulomatosis is a necrotizing vasculitis characterized by the triad of: (1) acute necrotizing granulomas of the upper respiratory tract (ENT), the lower respiratory tract (lung), or both; (2) necrotizing or granulomatous vasculitis affecting small to medium-sized vessels (e.g., capillaries, venules, arterioles, and arteries), most prominent in the lungs and upper airways; and (3) renal disease in the form of focal necrotizing, often crecentic, glomerulitis.

Patients who do not manifest the full triad are said to have "limited" Wegener granulomatosis, in which the involvement is restricted to the respiratory tract.

Front 188

188. What is the morphology of Wegener granulomatosis?

Back 188

Vascular lesions resemble those of acute PAN (sharply circumscribed arterial fibrinoid necrosis, w/associated neutrophilic infiltrates that may extend to the adventitia), but they are frequently accompanied by granuloma formation.

Front 189

189. What is the pathogenesis of Wegener granulomatosis?

Back 189

The resemblance to PAN and serum sickness suggest that Wegener granulomatosis may represent some form of hypersensitivity, possibly to an inhaled infectious or other environmental agent.

Immune complexes have been seen in the glomeruli and vessel walls in occasional patients.

Front 190

190. What are the clinical features of Wegener granulomatosis?

Back 190

Peak incidence is from ages 40-50 years. Typical symptoms include persistent pneumonitis w/bilateral nodular and vacitary infiltrates, chronic sinusitis, mucosal ulcerations of the naspharynx, and evidence of renal disease.

W/o treatment, 80% of pts die w/in 1 year; in contrast 90% respond to immunosuppression, particularly w/cyclophosphamide.

c-ANCA is present in more than 90% of pts w/active disease, and is a good marker of disease activity.

Front 191

191. What is lymphomatoid granulomatosis?

Back 191

Lymphomatoid granulomatosis is characterized by pulmonary nodules of lymphoid and plasmacytoid cells, often w/cellular atypia. It probably represents an evolving lymphoproliferative disorder, b/c up to 1/2 of pts develop a lymphoid malignancy, most commonly non-Hodgkin lymphoma.

This condition is sometimes difficult to differentiate from Wegener granulomatosis.

Front 192

192. What is thromboangiitis obliterans (Buerger disease)?

Back 192

Thromboangiitis obliterans is a distinctive disease that often leads to vascular insufficiency, and is characterized by segmental, thrombosing, acute and chronic inflammation of medium and small arteries, principally the tibial and radial arteries and sometimes secondarily extending to veins and nerves of the extremities.

*This disease is highly associated w/cigarette smoking; there is an increased prevalence of HLA-A9 and HLA-B5 in these pts.

Front 193

193. What is the morphology of thromboangiitis obliterans (Buerger disease)?

Back 193

Thomboangiitis obliterans is characterized by sharply segmental acute and chronic vasculitis of medium-sized an small arteries, mostly of the upper and lower extremities.

Microscopically, acute and chronic inflammation permeates the arterial walls, accompanied by thrombosis of the lumen, which may undergo organization and recanalization. Typically, the thrombus contains small microabscesses w/a central focus of neutrophils surrounded by grnulomatous inflammation.

Front 194

194. What are the complications of thromboangiitis obliterans (Buerger disease)?

Back 194

Later complications are chronic ulcerations of the toes, feet or fingers, and frank gangrene in some pts. In contrast to atherosclerosis, Buerger disease involves smaller arteries and is accompanied by severe pain, even at rest, related to the neural involvement.

Abstinence from cigarette smoking in the early stages of the disease often prevents further attacks.

Front 195

195. What is infectious arteritis?

Back 195

Localized arteritis may be caused by the direct invasion of infectious agents, usually bacteria or fungi, particularly Aspergillus and murcomycosis.

Vascular infections may weaken the arterial wall to result in a mycotic aneurysm or induce thrombosis and infarction.

Front 196

196. What is Raynaud phenomenon?

Back 196

Raynaud phenomenon refers to paroxysmal pallor or cyanosis of the digits of the hands or feet and, infrequently, the tips of the nose or ears (acral parts) owing to cold-induced vasoconstriction of the digital arteries, precapillary arterioles, and cutaneous AV shunts.

Front 197

197. What are the clinical features of Raynauds?

Back 197

Characteristically, the fingers change color in the sequence white-blue-red.

Raynauds reflects an exaggeration of normal central and local vasomotor responses to cold or emotion. It mostly affects young, otherwise healthy women.

Front 198

198. What is secondary Raynaud phenomenon

Back 198

Secondary Raynauds refers to arterial insufficiency of the extremities caused by various conditions, including SLE, scleroderma, atherosclerosis, or Buerger disease.

Features suggestive of secondary Raynaud phenomenon include age of onset > 30 years, more severe episodes, associated skin lesions, and clinical features of CT disease.

Front 199

199. What is the morphology of varicose veins?

Back 199

Veins with varicosities are dilated, tortuous, elongated, and scarred, with thinning at the points of maximal dilation.

Intrluminal thrombosis and valvular deformities (thickening, rolling, and shortening of the cusps) are freq discovered when the vessels are opened.

Frequently there is elastic tissue degradation and spotty calcifications within the media (phlebosclerosis).

Front 200

200. What is the clinical course of varicose veins?

Back 200

Vein dilation or deformation renders the valves incompetent, w/consequent stasis, persistent edema, and trophic skin changes, ultimately resulting in stasis dermatitis and ulceration (varicose ulcers).

Affected tissues may have impaired circulation and poor healing.

Front 201

201. Are embolisms common in varicose veins?

Back 201

No, embolism or other serious complication is very rare. This is in sharp contrast to the relatively frequent thromboembolism that arise from DVT.

Front 202

202. What is thrombophlebitis and phlebothrombosis?

Back 202

The deep leg veins account for more than 90% of cases for thrombophlebitis and phlebothrombosis, two designations for inflammation and venous thrombosis.

Predisposing factors for DVT include CHF, neoplasia, pregnancy, postoperative state, prolonged immobilization or local infection. Although 90% occur in deep leg veins, periprostatic plexus in men and ovarian and pelvic veins in women are other important site.

DVT are common sources of pulmonary emboli.

Front 203

203. What is migratory thrombophlebitis (Trousseau sign)?

Back 203

Migratory thrombophlebitis (Trousseau sign) is an entity consisting of multiple evanescent venous thrombi cropping up sporadically in multiple sites.

It is attributed to malignancy-associated hypercoagulability (particularly adenocarcinomas), and may be associated w/nonbacterial thrombotic endocarditis.

Front 204

204. What is plegmasia alba dolens (painful white leg)?

Back 204

This is a special variant of primary phlebothrombosis and refers to iliofemoral venous thrombosis occurring in pregnant women prior to or following delivery.

It is postulated that the thrombus initiates phlebitis, and the perivenous inflammatory response induces lymphatic blockage w/painful swelling.

Front 205

205. What is SVC syndrome?

Back 205

The SVC syndrome is usually caused by neoplasms compressing or invading the SVC (e.g., primary bronchogenic CA or mediastinal lymphoma). The resulting obstruction produces a distinctive complex manifested by dusky cyanosis and marked dilation of head, neck, and arm veins.

Front 206

206. What is IVC syndrome?

Back 206

The IVC syndrome is caused by similar processes. Moreover, certain neoplasms, particular HCC and renal cell CA, show a striking tendency to grow within veins, extending into the IVC and occasionally up to the heart.

IVC obstruction induces marked leg edema, distention of the lower abdominal superficial collateral veins, and when renal veins are involved - massive proteinuria.

Front 207

207. What is lymphatitis?

Back 207

Bacterial infections may spread into and thru the lymphatics to create acute inflammatory involvement in these channels (lymphangitis).

The most common etiologic agents are the group A beta-hemolytic stroptococci.

Lymphagitis presents as painful subcutaneous red streaks along involved lymphatics, with regional lymphadenopathy.

Front 208

208. What is obstructive lymphedema?

Back 208

Occlusion of lymphatic drainage is followed by the abnormal accumulation of interstitial fluid in the affected part, called obstructive lymphedema.

Front 209

209. What are the five causes of secondary lymphatic blockage?

Back 209

1. Spread of malignant tumors obstructing either the lymphatic channels or the regional lymph nodes
2. Radical surgical procedures w/removal of regional groups of lymph nodes
3. Postirradiation fibrosis
4. Filariasis
5. Postinflammatory thrombosis and scarring

Front 210

210. What causes primary lymphedema?

Back 210

In contrast, primary lymphedema may occur as an isolated congential defect or as the familial Milroy disease (heredofamilial congenital lymphoma).

A third form of primary lymphedema, AKA lymphedema praecox, appears btwn the ages 10-25 years, usually in females. Of unknown cause, the edema begins in the feet and slowly accumulates thru life.

Front 211

211. What are the consequences of chronic lymphedema in the subcutaneous tissue?

Back 211

Lymphedema leads to increased subcutaneous interstitial fibrous tissue, w/consequent enlargement of the affected part, brawny induration, "peau d'orange" appearance of the skin, and skin ulcers.

Front 212

212. What is bacillary angiomatosis?

Back 212

These are non-neoplastic reactive vascular proliferations.

Front 213

213. Where do most neoplasms of the blood and lymphatic vessels occur?

Back 213

Most lesions occur in soft tissues and viscera. Primary tumors of the large vessels (aorta, pulmonary artery, and vena cava) are extremely rare, most being connective tissue sarcomas.

Front 214

214. What are the two main differences between benign and malignant neoplasms in the blood vessels?

Back 214

1. Benign tumors produce readily recognized vascular channels filled w/blood cells or lymphatics w/transudate; these channels are lined by a layer of normal endothelial cells, w/o atypia.

2. Malignant tumors are more solidly cellular, w/cytologic anaplasia, including mitotic figures, and usually do not form well-organized vessels.

Front 215

215. What is a hemangioma?

Back 215

Hemangiomas are most commonly localized; however, some involve large segments of the body such as an entire extremity (agiomatosis). The majority are superficial lesions, often of the head or neck, but they may occur internally, w/nearly 1/3rd in the liver.

Front 216

216. What is a capillary hemangioma?

Back 216

Capillary hemangiomas are the most common type of vascular tumor; they occur primarily in skin or mucous membranes, but also in viscera. Tumors range from 1-2 mm to several cm in diameter.

All are well defined, unencapsulated lesions composed of closely packed aggregates of capillary-sized, thin-walled vessels. They may be partially or completely thrombosed.

Front 217

217. What are juvenile capillary (strawberry) hemangiomas?

Back 217

Juvenile capillary (strawberry) hemangiomas are a specific variant that are present at birth, grow rapidly for a few months, and begin regressing at age 1-3 years. Almost all disappear by age 7.

Front 218

218. What is the morphology of capillary hemangiomas?

Back 218

Varying in size from a few mm to several cm, hemangiomas are bright red to blue and are level w/the surface of the skin or slightly elevated.

Histologically, they are usually lobulated but unencapsulated aggregates of closely packed, thin-wall capillaries, usually blood filled and lined by a flattened endothelium, separated by scant connective tissue stroma.

Rupture of vessels causes scarring and accounts for the hemosiderin pigment occasionally found.

Front 219

219. What are cavernous hemangiomas?

Back 219

Less common than the capillary variety, cavernous hemangiomas share age and anatomic distribution, but they are usually larger, less well circumscribed, and more frequently involve deep structures than do capillary hemangiomas.

As they may be locally destructive and show no tendency to regress, many require surgery.

*Those in the brain are most threatening - in von Hippel-Lindau disease, they occur in the brain, cerebellum, and eye.

Front 220

220. What is the morphology of cavernous hemangiomas?

Back 220

Grossly, the usual cavernous hemangioma is a red-blue, soft, spongy mass 1-2 cm in diameter. Rarely, giant forms occur that affect large subcutaneous areas of the face, extremities, or other regions.

Histologically, the mass is sharply defined, but not encapsulated, and is made up of large, cavernous vascular spaces, partly or completely filled w/blood separated by a scant connective tissue stroma.

Intravascular thrombosis w/associated dystrophic calcification is common.

Front 221

221. What is a pyogenic granuloma (lobular capillary hemangioma)?

Back 221

This polypoid form of capillary hemangioma occurs as a rapidly growing exophytic red nodule attached by a stalk to the skin and gingival or oral mucosa. The lesions bleeds easily and is often ulcerated. Approx 1/3 of lesions develop after trauma. The proliferating capillaries are often accompanied by extensive edema and acute and chronic inflammatory infiltrate.

They have a striking resemblance to exuberant granulation tissue. Recurrence occurs infrequently as a solitary nodule or as satellite nodules.

Front 222

222. What is granuloma gravidarum?

Back 222

Granuloma gravidarum is a pyogenic granuloma that occurs in the gingiva or 1% of pregnant women and regresses after delivery.

These lesions, like the spider telangiectasias, highly the role of estrogen in vascular growth and proliferation.

Front 223

223. What is lymphangioma circumscriptum (capillary lymphangioma)?

Back 223

These lesions are composed of small lymphatic channels; they are typically 1-2 cm in diameter, exudate filled blister-like blebs, w/a predilection for head, neck and axillary subcutaneous tissue.

Histologically, they are composed of a network of endothelium-lined lymph spaces beneath the epidermis and **can be distinguished from capillary channels only by the absence of blood cells.**

Front 224

224. What is a cavernous lymphangioma (cystic hygroma)?

Back 224

Cavernous lymphangiomas occur in children in the neck or axilla and rarely retroperitoneally. They occasionally achieve considerable size, up to 15 cm in diameter, and may fill the axilla or produce gross deformities in the neck area. These lesions are not well encapsulated, and complete surgical resection can be difficult.

Microscopically, they are composed of highly dilated cystic spaces lined by endothelium w/scant stroma.

*Cystic hygromas of the neck occur in Turner syndrome

Front 225

225. What is a glomus tumor?

Where are they most commonly found?

Back 225

A glomus tumor is a biologically benign but often exquisitely painful tumor that arises from the modified smooth muscle cells of the glomus body, a specialized AV anastomosis that is involved in thermoregulation.

Glomus tumors are most commonly found in the distal portion of the digits, especially under the fingernails.

Front 226

226. What is the morphology of a glomus tumor?

Back 226

Grossly, the tumors are less than 1 cm in diameter, slightly elevated, rounded, red-blue, and firm, and may be pinpoint under the nail.

***Histologically, there are branching vascular channels separated by a connective tissue stroma that contains aggregates, nests, and masses of the specialized glomus cells that typically are arranged around vessels.*** Individual cells are usually small, regular in size, and round or cuboidal, w/scant cytoplasm and features very similar to SMC.

Front 227

227. What does telangiectasis mean?

Back 227

Telangiectasis designates a congenital anomaly or an acquired exaggeration of preformed vessels, composed of prominent capillaries, venules, and arterioles that creates a small focal red lesion, usually in the skin or mucous membranes.

Front 228

228. What is nevus flammeus?

Back 228

(Birthmark) This most common form of ectasia characteristically forms on the head and neck, is flat, and ranges in color from light pink to deep purple.

Histologically, these lesions show only dilation of vessels in the dermis.

Front 229

229. What is a port-wine stain?

Back 229

A special form of birthmark, this type may grow proportionately w/a child, thicken the skin surface, become unsightly, and demonstrate no tendency to fade.

Front 230

230. What is Sturge-Weber syndrome (AKA encephalotrigeminal angiomatosis)?

Back 230

Port-wine stains in the distribution of the trigeminal nerve may be associated w/Sturge-Weber syndrome, an extremely uncommon congenital disorder attributed to the faulty development of certain mesodermal and ectodermal elements.

Front 231

231. What are the clinical characteristics of Sturge-Weber syndrome?

Back 231

Sturge-Weber syndrome is characterized by venous angiomatous masses in the leptomeninges over the cortex and by ispilateral port-wine nevi of the face. It is associated w/mental retardation, seizures, hemiplegia, and radiopacities in the skull.

Thus, a large vascular malformation in the face may indicate the presence of more extensive vascular malformation in a child who exhibits some evidence of mental deficiency.

Front 232

232. What are spider telangiectasias?

Back 232

This non-neoplastic vascular lesion is a more or less radial and often pulsatile array of dilated subcutaneous arteries or arterioles about a central core that blanches when pressure is applied to its center.

These lesions tend to be on the face, neck. or upper chest and are most frequent in pregnant women and in patients w/cirrhosis. The hyperestrinism found in these two settings is believed to play a role in their development.

Front 233

233. What is Osler-Weber-Rendu disease?

Back 233

In the autosomal dominant Osler-Weber-Rendu disease, telangiectases are genetic malformations consisting of dilated capillaries and veins. They are present from birth and distributed widely over the skin and mucous membranes of the oral cavity, lips, and respiratory, GI, and urinary tracts. Rupture may occur, causing serious nosebleeds, bleeding into the gut, or hematuria.

Front 234

234. What is bacillary angiomatosis?

Back 234

Bacillary angiomatosis is an opportunistic infection in immunocompromised persons and manifests as vascular proliferations that clinically resemble tumors and involve skin, bone, brain, and other organs.

It is caused by infection with gram-negative bacilli of the Bartonella family, particularly Bartonella henselae, the organism that causes cat-scratch disease in immunocompetent person, and B. quintana, the cause of trench fever.

Front 235

235. What is the morphology of bacillary angiomatosis?

Back 235

Grossly, skin lesions have one or more red papules or nodular subcutaneous masses. Microscopically, these are tumor-like capillary proliferations composed of atypical ECs.

In contrast to pyogenic granuloma, Kaposi sarcoma, or angiosarcoma, there are also numerous neutrophils, nuclear dust, and purplish granular material (bacteria).

Tx is w/erythromycin.

Front 236

236. What are the four forms of Kaposi sarcoma?

Back 236

1. Chronic, or classic KS
2. Lymphadenopathic, or African KS
3. Transplant-associated KS
4. AIDS associated KS

Front 237

237. What is chronic or classic KS?

Back 237

Occurs primarily (90%)of older men in Eastern European descent (Ashkenazi Jews). This form is not associated w/HIV, but homosexual men may be at increased risk.

Clinically, chronic KS commences w/multiple red to purple skin plaques or nodules, primarily on the arms or legs, slowly increasing in size and number, spreading to more proximal sites and often becoming confluent.

The tumors freq remain asymptomatic and localized to the skin and subcutaneous tissues but are locally persistent, w/an erratic course of lapses and remissions.

Front 238

238. What is lymphadenopathic (African or edemic) KS?

Back 238

This form is common in portions of Africa and is common among young Bantu children of S. Africa. (Same regions of Burkitt lymphoma) They present w/generalized lymphadenopathy. Skin lesions are sparse.

W/the high prevalence of HIV-associate disease in Africa and the association with AIDS with KS, KS in HIV-negative and HIV-positive patients is now the most frequently occurring tumor in Central Africa.

Front 239

239. What is transplant associated KS?

Back 239

Transplant associated KS occurs typically several months to a few years postoperatively in organ transplant recipients who receive high doses of immunosuppressants.

This type of KS tends to be aggressive, involving lymph nodes, mucosa, and visceral organs in 1/2 of pts, and skin lesions may be absent.

Organ and internal involvement is usually fatal.

Front 240

240. What is AIDS-associated KS?

Back 240

KS is the msot common AIDS-associated cancer in the US.

W/the use of HAART, KS incidence has declined.

AIDS-associated KS lesions have no site of preference, but involvement of lymph nodes and the gut and wide dissemination tend to occur early in the course.

Front 241

241. What is the morphology of KS?

Back 241

Three stages can be identified: patch, plaque, and nodule.

The pathces are pink to red to purple solitary or multiple macules that are usually confined to the distal lower extremities or feet.

OVer times, lesiosn spread proximally, and usually convert into larger, violaceous raised plaques that reveal dermal, dilated, jagged, vascular channels lined by plump spindle cells.

A still later stage, the lesions may become nodular and neoplastic and may be composed of sheets of plump proliferating spindle cells.

Front 242

242. What are the characteristics of the nodular stage of KS?

Back 242

Particularly characteristic in this cellular background are scattered small vessels and slit-like spaces that often contain row of red cells and hyaline droplets.

Marked hemorrhage, hemosiderin pigment, lymphocytes, and occasional macrophages may be mixed with this cellular background.

The nodular stage is often accompanied by involvement of lymph nodes and of viscera, particular in the African and AIDS-associated KS.

Front 243

243. What is the pathogenesis of KS?

Back 243

Nearly all KS lesions are infected w/human herpesvirus 8, AKA KS-associated herpesvirus (KSHV).

This agent is both necessary and sufficient for KS development, although immunosupression is an important cofactor in disease pathogenesis and clinical expression.

*KSHV proteins may disrupt cellular control by inhibiting p53 and making a viral homologue of cyclin D67.

Front 244

244. What are hemangioendotheliomas?

Back 244

This term is used to denote a wide spectrum of vascular neoplasms showing histologic features and clinical behavior intermediate between the benign, well differentiated hemangiomas and the frankly malignant angiosarcomas.

Front 245

245. What is an epithelioid hemangioendothelioma?

Back 245

This a unique vascular tumor occurring around medium sized and large veins in the soft tissue of adults.

In such tumors, well-defined vascular channels are inconspicuous and the tumor cells are plump and often cuboidal, thus resembling epithelial cells.

The differential Dx includes metastatic CA, melanoma, and those sarcomas that assume an epithelioid appearance.

Front 246

246. What is an angiosarcoma?

Back 246

Angiosarcomas are malignant endothelial neoplasms w/structure varying from highly differentiated tumors that resemble hemangiomas (hemangiosarcoma) to whose whose anaplasia makes them difficult to distinguish from malignant neoplasms.

They occur in both sexes, more often in older adults, anywhere in the body but most commonly in the skin, soft tissue, breast, and liver.

Front 247

247. What are hepatic angiosarcomas?

Back 247

The rare hepatic angiosarcomas are associated w/distinct carcinogens (arsenic, Thorotrast, and PVC).

With all three agents, there is a very long latent period of many years btwn exposure and the development of tumors.

Front 248

248. What is the morphology of angiosarcomas?

Back 248

Grossly, cutaneous angiosarcoma may begin as small, well-demarcated red nodules evolving into large, fleshy, gray-white soft tissue masses.

*Microscopically, all degrees of differentiation of these tumors may be found.

EC derivation is demonstrated by staining for CD31, CD34, or vWF.

Front 249

249. What is a hemangiopericytoma?

Back 249

Hemangiopericytoma is a tumor of pericytes, most commonly arising on the lower extremities (especially the thigh) or in the retroperitoneum.

50% metastasize. Most are small, but can grow up to 8 cm. Microscopically, they are composed of numerous capillary channels encased by nests and masses of spindle-shaped to round cells extrinsic to the EC basement membrane (resembling pericytes).

Front 250

250. What are the key elements of luminal expansion in angioplasty?

Back 250

1. Plaque rupture
2. Medial dissection
3. Stretching of the media of the dissected segment

Front 251

251. What is proliferative restenosis?

Back 251

The long-term success of angioplasty is limited by the development of proliferative restenosis, which results from intimal thickening and occurs in approx 30-50% of pts w/in the first 4-6 mos following angioplasty.

The factors causing restenosis probably relate to muscle cell injury, elaboration of cytokines and growth factors from the inflammatory cells in the plaque, local thrombosis, and elastic recoil of the dilated segment.

Front 252

252. What are the most widely used small vessel replacement?

Failing of the small vessel prostheses is due to...?

Back 252

Aulogous saphenous vein (pt's own vein) and expanded polytetrafluoroethylene (a spongy Teflon fabric).

Failing of the small diameter prostheses are frequently due to thrombotic occlusion, intimal fibrous hyperplasia, or occasionally atherosclerosis.

Front 253

253. CABG surgery grafts are done with what prostheses?

Back 253

Bypasses are done using grafts of either reversed autologous saphenous vein, or internal mammary artery (usually the left internal mammary artery, owing to proximity to the heart).

***Internal mammary artery grafts have a greater than 90% patency at 10 years, vs. only 50% patency with saphenous vein grafts.