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346 Cards in this Set

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  • Back
1. What is cardiac output?
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.
2. What is venous return?
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.
3. What four factors directly affect cardiac output?
1. The basic level of body metabolism
2. Whether the person is exercising
3. The person's age
4. Size of the body
4. What are the average COs for young healthy men and women?
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
5. What is the cardiac index?
Cardiac index is the cardiac output per square meter of body surface area.
6. What is the effect of age on cardiac index?
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
7. What primarily controls the cardiac output?
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.
8. What is the Frank-Starling law of the heart?
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.
9. What other important factors control the cardiac output?
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.
10. Summary of cardiac output regulation
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.
11. What is the relationship between the total peripheral resistance and the cardiac output?

What is the equation for CO?
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)
12. What factors can cause a hypereffective heart?
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
13. What factors cause a hypoeffective heart?
Any factor that decreases the heart's ability to pump blood causes hypoeffectivity.

These include:
Inhibition of sympathetic stimulation
Abnormal HR or rhythm
Valvular heart disease
Increased arterial pressure
Congenital heart disease
Cardiac hypoxia
14. What is the role of the nervous system in controlling CO?
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.
15. What happens to the arterial pressure during exercise?
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
16. What is the one common factor in conditions that commonly cause CO's higher than normal?
They all result from chronically reduced total peripheral resistance.
17. What are these conditions that decrease the peripheral resistance while at the same time increase the CO?
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.
18. What are the two categories of conditions that cause low CO?
1. Those abnormalities that cause the pumping effectiveness to fall too low

2. Those that cause venous return to fall too low
19. What are the conditions that cause low CO via decreased pumping efficacy?
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.
20. What are the conditions that cause low CO via non-cardiac peripheral factors (i.e. decreased venous return)?
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.
21. What is the effect of increased external pressure outside the heart on CO curves?
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.
22. What are some of the factors that can alter the intrapleural pressure?
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.
23. What three principal factors affect venous return to the heart from the systemic circulation?
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.
24. What is the relationship between venous return and right atrial pressure?
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.
25. What is mean systemic filling pressure?
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.
26. What happens when the atrial pressure becomes more negative?
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.
27. What is the cause of this plateau in venous return?
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.
28. What is mean circulatory filling pressure?
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.
29. What is the effect of blood volume on mean circulatory filling pressure?
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.
30. What is the effect of sympathetic nervous stimulation of the circulation on mean circulatory filling pressure?
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.
31. How does the mean systemic filling pressure relate to mean circulatory filling pressure?
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.
32. How do changes in the mean systemic filling pressure affect the venous return curve?
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.
33. What is the pressure gradient for venous return?
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.
34. What is resistance to venous return?
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.
35. Why is the resistance to venous return important?
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.
36. How does one determine the resistance to venous return?
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
37. What is the highest level to which the right atrial pressure can rise?
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.
38. How does the heart and systemic circulation operate together?
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
39. What is the effect of increased blood volume on CO?
A sudden increase in blood volume increases the CO.
40. Why does the greatly increased CO caused by increased blood volume only last for a few minute?

Three reasons...
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.
41. What are the effects of sympathetic stimulation on cardiac output?
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.
42. What is the effect of sympathetic inhibition on CO?
1. The mean systemic filling pressure falls
2. The effectiveness of the heart as a pump decreases
43. What happens when one opens a large AV fistula?
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
44. What are the two methods used for measuring CO?
1. Oxygen Fick method
2. Indicator dilution method
45. Oxygen Fick method
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)
46. Indicator dilution method
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.
47. Cardiac failure
Failure of heart to pump enough blodo to satisfy needs of the body; can result from any heart condition that reduces the ability of the hear to pump blood.

Cause usually is decreased contractility of the myocardium resulting result from diminished coronary blood flow
48. Acute effects of moderate cardiac failure
Heart is immediate depressed causing:
1. Reduced cardiac output
2. Damming of blood in the veins (increased venous pressure)

Low cardiac output is still sufficient to sustain life for perhaps a few hours but is likely to be associated w/fainting; this acute phase only lasts for a few seconds b/c sympathetic nerve reflexes occur immediately and compensate to a great extent for the damaged heart.
49. Compensation for Acute Cardiac Failure by Sympathetic Nervous Reflexes
Best known of the reflexes is the baroreceptor reflex which is activated by diminished arterial pressure; chemoreceptor reflex, the CNS ischemic response, and reflexes that originate in the damaged heart also contribute.

Sympathetic become strongly stimulated w/in a few seconds and parasympathetic signals become reciprocally inhibited
50. Effects of sympathetic stimulation on circulation
If ventricular musculature is damaged but still functional, sympathetic stimulation strengthens the damages musculature.

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

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

Increased filling pressure greatly increases tendency for blood to flow from the veins back into the heart
51. Priming of sympathetic reflexes - how long does it take?
They become maximally developed in about 30 seconds
52. Semi-chronic state of cardiac failure
Characterized by mainly 2 events:

1. Retention of fluid by the kidneys
2. Varying degrees of recovery of the heart itself over a period of weeks to months
53. Effect of low CO on renal function
In general, urine output remains reduced below normal as long as the CO and arterial pressure remain significantly less than normal

Urine output does not usually return all the way tot normal after an acute MI until the CO and arterial pressure rise all the way back to normal or almost normal
54. Method of venous return increase
Increased blood volume increases the mean system filling pressure which increases the pressure gradient for causing the venous flow of blood toward the heart and distends the veins which reduces the venous resistance and allows even mroe ease of flow of blood to the heart.

If the heart is not too damaged, increased venous return can often fully compensate for the hearts diminished pumping ability.
55. What are three detrimental effects of excess fluid retention post MI?
1. Overstretching of the heart
2. Edema and consequent deoxygenation of the blood
3. Development of extensive edema in most parts of the body
56. Limited benefits of excess fluid retention post MI
Because the heart is already pumping at its maximum pumping capacity, this excess fluid no longer has a beneficial effect on the circulation. Instead, severe edema develops throughout the body, which can be very detrimental in itself and can lead to death.
57. What is compensated heart failure?
Increase in right atrial pressure can maintain the CO at a normal level despite continued weakness of the heart, thus many people have normal resting CO but mildly to moderately elevated right atrial pressures b/c of various degrees of compensated heart failure

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

Any attempt to perform heavy exercise usually causes immediate return of the symptoms of acute failures b/c the heart is unable to increase its pumping capacity
58. Dynamics of severe cardiac failure
No amount of compensation, either by sympathetic nervous reflexes can make the excessively weakened heart pump a normal CO.

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

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

This decompensated heart failure which is clinically detected by bubbling rales in the lungs and dyspnea
59. Treatment of decompensation
The decomposition process can often be stopped by:

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

2. Administering diuretic drugs to increase kidney excretion while reducing water and salt intake which brings about a balance between fluid intake and output despite low CO
60. What is the MOA of the Cardiotonic Drugs Such as
Believed to strengthen heart contractions by increasing the quantities of calcium ions in muscle fibers.

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

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

This allows the muscle fiber intracellular calcium level to rise slightly
61. Unilateral left heart failure
In a large number of patients, especially those with early acute failure, left-sided failure predominates over rightsided failure

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

Mean pulmonary filling pressure rises; pulmonary vascular congestion and edema occur
62. Vicious circle of cardiac deterioration
Low arterial pressure that occurs during shock reduces coronary blood supply. This makes the heart still weaker, which makes arterial pressure still more, which worsens shock, and you die.

In a heart w/an already block major coronary vessel, deterioration sets in when coronary arterial pressure falls below 80-90 mm Hg.
63. Procedures performed to save patients in cardiogenic shock
Surgically removing the clot in the coronary artery often in combination with CABG or catheterizing the blocked coronary artery and infusing either streptokinase or TPA enzymes the dissolve the clot

Little benefit of these procedures after 3 hours.
64. Can acute cardiac failure cause peripheral edema?
Almost never causes immediate peripheral edema.

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

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

It often causes a fall in peripheral capillary pressure rather than a rise
65. What is the cause of peripheral edema in non-acute heart failure?
After the first day of overall heart failure or right-ventricular heart failure, peripheral edema does begin to occur solely b/c of fluid retention by the kidneys.

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

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

Therefore, the capillary pressure now also rises markedly, causing loss of fluid into the tissues and development of severe edema
66. What are the three known causes of reduced renal output of urine during cardiac failure?
1. Decreased glomerular filtration because of reduced arterial pressure and intense sympathetic constriction of the afferent arterioles of the kidney

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

3. Increased aldosterone secretion
-Large quantities of aldosterone are secreted by the adrenal cortex due to the activation of the angiotensin system and b/c of increased potassium ion concentration as a result of heart failure
67. Why do elevated adosterone levels lead to antidiuretic hormone secretion?

What is the result of this after cardiac failure?
The elevated aldosterone further increases the reabsorption of sodium from the renal tubules. This leads to a secondary increase in water reabsorption for two reasons:

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

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

This elicits the antidiuretic hormone secretion by the HPA axis, which promotes a still greater increase in tubular reabsorption of water
68. What is Atrial natriuretic factor (ANF)?
ANF is a hormone released by the atrial walls of the heart when they become stretched; increases in blood 5-10x due to severe heart failure.

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

Therefore, ANF plays a natural role to help prevent extreme congestive symptoms during cardiac failure.
69. Acute pulmonary edema in late-stage heart failure
Frequent cause of death in heart failure in patients who have already had chronic heart failure for a long time.

When this occurs in a person w/o new cardiac damage, it usually is set off by some temporary overload of the heart.
70. Acute pulmonary edema vicious circle
1. Temp increased load on the already weak ventricle initiates viscous circle; blood begins to dam up in the lungs
2. Increased blood in lungs elevates the pulmonary capillary pressure, and a small amt of fluid begins to transude into the lung tissues and alveoli
3. The increased fluid in lungs diminishes the degree of oxygenation in the blood
4. The decreased O2 in the blood further weakens the heart and arterioles everywhere in body; leading to peripheral vasodilation
5. Peripheral vasodilation increases venous return of blood to even more
6. Increased venous return further increases damming of the blood in the lungs, leading to still more transudation of fluid, more O2 desaturation, more venous return, and so forth.
71. What are five types of "heroic" therapeutic measures that can reverse the process of an acute pulmonary edema vicious circle?
1. Putting tourniquets on both arms and legs to sequester much of the blood in the veins, and, therefore, decrease the workload on the left side of the heart
2. Bleeding the patient
3. Giving a rapidly acting diuretic, such as furosemide, to cause rapid loss of fluid from the body
4. Giving the patient pure O2 to breath to reverse the blood O2 desaturation
5. Giving the patient a rapidly acting cardiotonic drug, such as digitalis, to strengthen the heart
72. What is the cardiac reserve?
The max percentage that the cardiac output can increase above normal

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

Athletes: 500-600%
73. What can decrease the cardiac reserve?
Any factor that prevents the heart from pumping blood satisfactorily will decrease the cardiac reserve.

This can result from ischemic heart disease, primary myocardial disease, vitamin deficiency that affects cardiac muscle, physical damage to the myocardium, valvular heart disease, and many other factors
74. Dx of low cardiac reserve
Usually can be made by requiring the person to exercise either on a treadmill or by walking up and down steps, either of which requires greatly increased cardiac output

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

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

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

3. Excessive increase in heart rate b/c the nervous reflexes to the heart overreact in an attempt to overcome the inadequate CO
76. Normal cardiac output and venous return?

Normal right atrial pressure?
Normal cardiac output and venous return: 5 L/min

Normal right atrial pressure: 0 mm Hg
77. Effect of an acute MI on the right atrial pressure and CO
Cardiac output falls to 2 L/min

Right atrial pressure rises immediately to 4 mm Hg
78. Effect of sympathetic reflexes 30 sec after MI on CO, venous return, and right atrial pressure?
Increases the mean systemic filling pressure

Cardiac output then increases to 4 L/min

Right atrial pressure rises to 5 mm Hg
79. Effect of compensation few days after acute MI on CO, right atrial pressure and renal output?
Cardiac output returned to normal: 5 L/min

Right atrial pressure has risen still further to 6 mm Hg

B/c the cardiac output is now normal, renal output is also normal, so that a new state of equilibrated fluid balance has been achieved
80. Decompensation following acute MI
Results from the fact that the cardiac output never rises to the critical level of 5 L/min needed to re-establish normal kidney excretion of fluid that would be required to cause balance between fluid input and output.

Leads to vicious circle so that further retention of fluid causes only more severe cardiac edema and a detrimental effect on cardiac output. The condition accelerates downhill until death occurs
81. Treatment of decompensated heart disease
Use digitalis to strengthen the heart so that the cardiac output can reach the critical level required for the kidneys to excrete normal amounts of urine.

Causes diuresis due to high fluid output in urine.

Also reduces the mean systemic filling pressure and reduces the right atrial pressure as a result of less fluid buildup and the the circulatory system has now stabilized
82. Two causes of high output cardiac failure
1. Arteriovenous fistula that overloads the heart b/c of excessive venous return even though the pumping capability of the heart is not depressed

2. Beriberi, in which the venous return is greatly increased b/c of diminished systemic vascular resistance, but at the same time, the pumping capability of the heart is depressed
83. What are the lub and dub sounds associated with?
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.
84. What is the cause of the first and second heart sounds?
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.
85. Duration and pitch of each of the heart sounds?
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.
86. Why does the second heart sound have a higher frequency?
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.
87. What is the third heart sound?
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.
88. What is the fourth heart sound?
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.
89. Areas for listening to the different heart sounds
Not directly over teh 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
90. What are rheumatic valvular lesions?
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.
91. How does the streptococcal toxin initiate the rhematic valvular lesions?
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.
92. Which valves are affected in rheumatic fever?
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.
93. Scarring of the valves in rheumatic fever
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.
94. What happens to the scarred heart valves?
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.
95. What is a common finding heard in aortic stenosis?
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"
96. What is a common finding heard in aortic regurgitation?
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.
97. What is a common finding heard in mitral regurgitation?
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.
98. What is a common finding heard in mitral stenosis?
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.
99. In sum, which murmurs occur during systole, and what occur during diastole?
Systole: Aortic stenosis and mitral regurgitation

Diastole: Aortic regurgitation and mitral stenosis
100. In aortic stenosis and aortic regurgitation, how is the net stroke volume output of the heart affected?
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
101. How does hypertrophy of the left ventricle compensate?
Sometimes the left ventricular muscle mass increases 4-5x to create a force strong enough to overcome regurgitation or stenosis.
102. In compensation, what does the increased blood volume result from?

What is the effect of an increased blood volume?
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.
103. What happens when the aortic stenosis/regurgitation progress to or beyond a critical stage?
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.
104. What are some consequences of mitral stenosis/regurgitation?
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
105. What causes the pulmonary edema in mitral valvular disease?
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.
106. Consequences of an enlarged left atrium
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).
107. What is the compensation that occurs in early mitral valvular disease?
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.
108. What can occur in patients w/aortic valvular lesions during exercise?

What about those w/mitral disease?
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.
109. What are the three major types of congenital anomalies of the heart?
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.
110. Why does the ductus arteriosus close after birth?
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.
111. Specifically, what causes the ductus arteriosus?
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 int eh ductus wall.
112. Recirculation through the lungs in PDA
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.
113. What is a consequence of a PDA on cardiac and respiratory function?
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.
114. What is the characteristic sound of a PDA?
Machinery murmur that waxes and wanes with each beat of the heart
115. What are the four conditions that occur simultaneously in Tetralogy of Fallot?
1. Overriding aorta
2. Pulmonary artery stenosis
3. VSD
4. Right ventricular hypertrophy

Most common cause of blue baby.
116. Dx of Tetralogy of Fallot is based on what four things?
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.
117. What is one cause of congenital heart defects?
Defects are particularly prone to develop when the expectant mother contracts German measles.
118. What are 4 methods of oxygenating blood?
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.
119. What are the two major sources where water is added to the body?
1. It is ingested in the form of liquids or water in the food, which together normally add about 2.1 L/day to the body fluids

2. It is synthetized in the body as a result of oxidation of carbohydrates, adding about 200 ml/day

This provides a total water intake of about 2.3 L/day.
120. What is insensible water loss?
There is a continuous loss of water by evaporation from the respiratory tract and diffusion thru the skin. This is termed insensible water loss b/c we are not consciously aware of it, even though it occurs continually.

The insensible water loss occurs independently of sweating and is present even in people who are born without sweat glands.
121. Water loss in feces
Only a small amt of water (100 ml/day) normally is lost in the feces.

This can increase to several liters a day in people with severe diarrhea. For this reason, severe diarrhea can be life threatening if not corrected within a few days.
122. Water loss by the kidneys
The most important means by which the body maintains a balance between water intake and output, as well as a balance between intake and output of most electrolytes in the body, is by controlling the rates at which the kidneys excrete these substances.
123. What are the two compartments in which the body fluid is distributed?
1. Extracellular fluid (ECF)
-subdivides into interstitial fluid and blood plasma

2. Intracellular fluid (ICF)

3. Transcellular fluid (not major)
-includes fluid in the synovial, peritoneal, pericardial, and intraocular spaces, as well as the CSF fluid.
124. About how much of an adult human is water weight?
About 60%, or about 42 liters.
125. Intracellular fluid compartment
About 28 of the 42 L of fluid in the body are inside cells and are collectively called the ICF. Thus, the ICF constitutes about 40% of the total body weight in an average person.
126. Extracellular fluid compartment
All the fluids outside the cells are collectively called the ECF.

Together these fluids account for about 20% of the body weight, or about 14 L.

The interstitial fluid makes up more than 3/4ths of the ECF, and the plasma makes up almost 1/4th of the ECF.
127. Blood volume
Blood contains both ECF and ICF.

However, blood is considered to be a separate fluid compartment b/c it is contained in a chamber of its own, the circulatory system.

The avg blood volume of adults is about 7% of body weight, or about 5 L.

About 60% of the blood is plasma and 40% is RBCs.
128. What is hematocrit?
The hematocrit is the fraction of the blood composed of RBCs. True HCT is only about 96% of the measured HCT.

In men, the measured HCT is normally about 0.40 and in women it is about 0.36.
129. What is the ionic composition of plasma and interstitial fluid?
B/c the plasma and interstitial fluid are spearated only by highly permeable capillary membranes, their ionic composition is similar. The most important difference between these two compartments is the higher concentration of protein in the plasma; b/c the capillaries, only small amounts of proteins are leaked into the interstitial spaces in most tissues.
130. What is the Donnan effect?
B/c of the Donnan effect, the concentration of cations is slightly greater in the plasma than in the interstitial fluid. The plasma proteins have a net negative charge and, therefore, tend to bind cations, such as sodium and potassium, thus holding extra amounts of these cations int he plasma along with the plasma proteins.

Conversely, anions tend to have a slightly higher concentration in the interstitial fluid compared with the plasma, b/c the negative charges of the plasma proteins repel the anions.
131. What are the important constituents of the ICF?
The ICF is separated from the ECF by a cell membrane that is highly permeable to water but not to most of the electrolytes in the body.

The ICF contains only small quantities of sodium and chloride ions and almost no calcium ions.

Instead, it contains large amts of potassium and phosphate ions plus moderate quantities of magnesium and sulfate ions, all of which have low concentrations int he ECF. Also, cells contain large amounts of protein, almost 4x as much as in the plasma.
132. What is the indicator dilution principle?
This method is based on the principle of conservation of mass. This means that the total mass of a substance after dispersion in the fluid compartment will be the same as the total mass injected into the compartment.

This method is used to measure the volume of virtually any compartment in the body as long as (1) the indicator disperses evenly thru the compartment, (2) the indicator disperses only in the compartment that is being measured, and (3) the indicator is not metabolized or excreted.
133. How does one determine the total amount of water in the body?
Radioactive water (tritium) or heavy water can be used to measure total body water. These forms of water mix with the total body water w/in a few hours after being injected into the blood, and the dilution principle can be used to calculate total body water.
134. What is antipyrine?
Another substance that has been used to measure total body water is antipyrine, which is very lipid soluble and can rapidly penetrate cell membranes and distribute itself uniformly through the ICF and ECF compartments.
135. How does one measure ECF volume?
The volume of ECF can be estimated using any of several substances that disperse in the plasma and interstitial fluid but do not readily permeate the cell membrane.

They include radioactive sodium, chloride, iothamate, thiosulfate ion, and inulin.

Some of these substances may diffuse into the cells in small amounts.
136. What is the equation for calculating intracellular volume?
The intracellular volume cannot be measured directly. However, ti can be calculated as:

Intracellular volume = (total body water) - (extracellular volume)
137. How does one measure plasma volume?
To measure plasma volume, a substance must be used that does not readily penetrate capillary membranes but remains in the vascular system after injection.

One of the most commonly used substances for this purpose is serum albumin labeled with radioactive iodine.

Also, dyes that avidly bind to the plasma proteins, such as Evans blue dye, can be used to measure plasma volume.
138. What is the equation for calculating interstitial fluid volume?
Intersitital fluid volume = (ECF volume) - (Plasma volume)
139. How does one measure blood volume?
Blood volume can be calculated if one knows the HCT value.

Total blood volume = (Plasma volume) / (1 - HCT)

Another way is to inject RBCs that have been labeled w/radioactive material and then measure with the indicator dilution method.
140. What determines the distribution of fluid between intracellular and extracellular compartments?
Determined mainly by the osmotic effect of the smaller solutes - especially sodium, chloride, and other electrolytes- acting across the cell membrane.
141. What is the definition of osmosis?

What is the "rate of osmosis"
Osmosis is the net diffusion of water across a selectively permeable membrane from a region of high water concentration to one that has a lower water concentration.

Water then diffuses from a region of low solute concentration to one with a high solute concentration.

The rate of diffusion of water is called the rate of "osmosis."
142. What is the difference between moels and osmoles?
One osmole is equal to 1 mole of solute particles.

Need to take into account dissociation of compounds into ions, such as NaCl, which would be 1 mol/L in moles but 2 osm/L in osmoles.
143. What is the difference between osmolality and osmolarity?
Osmolality = osm/Kg of water

Osmolarity = osm/L of solution.
144. What is the osmotic pressure?
Osmosis of water molecules across a selectively permeable membrane can be opposed by applying a pressure in the direction opposite that of the osmosis. The precise amt of pressure required to prevent the osmosis is called the osmotic pressure.

Osmotic pressure is an indirect measurement of the water and solute concentrations of a solution.
145. What is the relation between osmotic pressure and osmolarity?
The osmotic pressure of a solution is directly proportional to the concentration of osmotically active particles in that solution.

According to van't Hoff's law, osmotic pressure (п) can be calculated as:

п = CRT

where C is the concentration of solutes in osm/L, R is the ideal gas constant, and T is the temp in kelvin.
146. What is the point of an osmotic coefficient?
The van't Hoff calculation is only an approximation, b/c sodium and chloride ions do not behave entirely independently in solution b/c of interionic attraction between them. One can correct for these deviations by using a correction factor called the osmotic coefficient.
147. Osmolarity of the body fluids
About 80% of the total osmolarity of the interstitial fluid and plasma is due to sodium and chloride ions, whereas for intracellular fluid, almost half the osmolarity is due to potassium ions, and the remainder is divided among many other intracellular substances.
148. Difference in osmolarity of the plasma and interstitial and intracellular fluids
The plasma is about 1 mOsm/L greater than that of the interstitial and intracellular fluids.

This slight difference is caused by the osmotic effects of the plasma proteins, which maintain about 20 mm Hg greater pressure in the capillaries than in the surrounding interstitial spaces.
149. For each mOsm concentration gradient of an impermeant solute, about how much osmotic pressure is exerted across the cell membrane?
About 19.3 mm Hg for one mOsm

This demonstrates the large force that can move water across the cell membrane when the intracellular and extracellular fluids are not in osmotic equilibrium.
150. What happens to a cells if it is placed in a hypotonic solution?
The cell will swell as water diffuses in the cell.
151. What happens to a cells if it is placed in a hypertonic solution?
The cell will shrink as water flows out of the cell into the solution
152. What do isosmotic, hyperosmotic, and hypo-osmotic fluids mean?
Solutions with an osmolarity the same as the cell are called isosmotic.

The terms hyperosmotic and hypo-osmotic refer to solutions that have a higher or lower osmolarity, respectively, compared w/the normal ECF, without regard for whether the solute permeates the cell membrane.
153. About how long does it take to achieve osmotic equilibrium everywhere in the body after drinking water?

Why does it take this long?
About 30 min.

The fluid usually enters the body thru the gut and must be transported by the blood to all tissues before complete osmotic equilibrium can occur.
154. What are the two basic principles regarding the type of therapy that should be instituted?
1. Water moves rapidly across cell membranes; therefore, the osmolarities of intracellular and extracellular fluids remain almost exactly equal to each other except for a few minutes after a change in one of the compartments.

2. Cell membranes are almost completely impermeable to many solutes; therefore, the number of osmoles in the extracellular or intracellular fluid generally remains constant unless solutes are added to or lost from the extracellular compartment.
155. What is the net effect when a hypertonic solution is added to the ECF?
Increase in extracellular volume, a decrease in intracellular volume, and a rise in osmolarity in both compartments.
156. What is the net effect when a hypotonic solution is added to the ECF?
Both the intracellular and extracellular volumes are increased by the addition of hypotonic fluid, although the intracellular volume increases to a greater extent.
157. What happens when one adds 2 liters of a hypertonic NaCl solution?
The addition of 2 L of hypertonic NaCl solution causes more than a 5 L increase in ECF volume while decreasing ICF volume by almost 3 L.
158. What are glucose solutions used for?
Many types of solutions are administered via IV to provide nutrition to people who cannot otherwise take adequate amounts of nutrition.

After the glucose or other nutrients are metabolized, an excess of water often remains, esp if additional fluid is ingested. The kidneys excrete this in the form of a very dilute urine so all that's left is the addition of nutrients to the body.
159. What is the primary measurement that is readily available to the clinician for evaluating a patient's fluid status?
The plasma sodium concentration.

When a plasma Na concentration is reduced below around 142 mEq/L, a person is said to have hyponatremia.

When a plasma Na concentration is elevated above 142 mEq/L, a person is said to have hypernatremia.
160. What causes hyponatremia?
Decreased Na concentration can result form loss of NaCl form the ECF or addition of excess water to the ECF.
161. What is hypo-osmotic dehydration?
Caused by a primary loss of NaCl.

Results in:
↓ Plasma Na concentration
↓ ECF volume
↑ ICF volume

Caused by:
1. Adrenal insufficiency
2. Overuse of diuretics
3. Diarrhea
4. Vomiting
5. Addison's disease
162. What is hypo-osmotic overhydration?
Excess water retention dilutes the sodium in the ECF.

Results in:
↓ Plasma Na concentration
↑ ECF volume
↑ ICF volume
163. What causes hypernatremia?
Can be due to either loss of water from the ECF, which concentrates Na ions, or excess sodium in the ECF.
164. What is hyper-osmotic dehydration?
Caused by a primary loss of water from the ECF.

Results in:
↑ Plasma Na concentration
↓ ECF volume
↓ ICF volume

Caused by:
1. Diabetes insipidus
2. Excessive sweating
3. Dehydration caused by water intake that is less than water loss
165. What is hyper-osmotic overhydration?
Occurs as a result of excessive NaCl added to the ECF. This causes overhydration b/c excess NaCl is usually associated w/at least some degree of water retention.

Results in:
↑ Plasma Na concentration
↑ ECF volume
↓ ICF volume

Caused by:
1. Cushing's disease
2. Primary aldosteronism*

*not as severe b/c increased aldosterone secretion causes the kidneys to reabsorb greater amounts of water as well as sodium.
166. What two conditions are especially prone to cause intracellular swelling?
1. Depression of the metabolic systems of the tissues
2. Lack of adequate nutrition to the cells

Also, inflammation usually has a direct effect on the cell membranes to increase their permeability.
167. What are the two general causes of extracellular edema?

What is the most common clinical cause of interstitial fluid accumulation?
1. Abnormal leakage of fluid from the plasma to the interstitial spaces across the capillaries
2. Failure of the lymphatics to return fluid from the interstitium back into the blood.

The most common clinical cause of interstitial fluid accumulation is excessive capillary fluid filtration.
168. What three changes can increase the capillary filtration rate?
Any one of the following changes can increase the capillary filtration rate:

1. Increased capillary filtration coefficient
2. Increased capillary hydrostatic pressure
3. Decreased plasma colloid osmotic pressure
169. How does lymphatic blockage cause edema?
When lymphatic blockage occurs, edema can become especially severe b/c plasma proteins that leak into the interstitium have no other way to be removed.

The rise in protein concentration raises the colloid osmotic pressure of the interstitial fluid, which draws even more fluid out of the capillaries.
170. Filaria nematodes
Blockage of lymph flow can be especially severe with infections of the lymph nodes, such as occurs with infection by filaria nematodes.
171. Edema caused by heart failure
In heart failure, the heart fails to pump blood normally from the veins into the arteries; this raises the venous pressure and capillary pressure, causing increased capillary filtration.

In addition, the arterial pressure tends to fall, causing decreased excretion of salt and water by the kidneys, which increases blood volume and further raises capillary hydrostatic pressure to cause still more edema.
172. Edema caused by decreased kidney excretion of salt and water
The main effects of this are to cause:

1. Widespread increases in interstitial fluid volume (extracellular edema)
2. Hypertension, b/c of the increase in blood volume
173. Edema caused by decreased plasma proteins
A reduction in plasma concentration of proteins b/c of either failure to produce normal amounts of proteins or leakage of proteins form the plasma causes the plasma colloid osmotic pressure to fall, which leads to increased capillary filtration throughout the body as well as extracellular edema.
174. What are two of the most important causes of decreased plasma protein concentration?
Loss of proteins in the urine in certain kidneys diseases, a condition referred to as nephrotic syndrome (MOST IMPORTANT)

Also, cirrhosis of the liver is another condition that causes a reduction in plasma protein concentration since the liver cells fail to produce sufficient plasma proteins.
175. Ascites
Liver fibrosis sometimes compresses the abdominal portal venous drainage vessels as they pass thru the liver before emptying back into the general circulation.

Blockage of this portal venous outflow raises capillary hydrostatic pressure throughout the GI area and further increases filtration of fluid out of the plasma into the intra-abdominal areas.

When this occurs, the combined effects of decreased plasma protein concentration and high portal capillary pressures cause transudation of large amts of fluid and protein into the abdominal cavity, a condition referred to as ascites.
176. What are the three major safety factors that prevent excessive fluid accumulation in the interstitial spaces?
1. Low compliance of the interstitium when interstitial fluid pressure is in the negative pressure range
2. The ability of lymph flow to increase 10-50x
3. Washdown of interstitial fluid protein concentration, which reduces interstitial fluid colloid osmotic pressure as capillary filtration increases.
177. How does the low compliance of the tissues in the negative pressure range act as a safety factor against edema?
When interstitial fluid hydrostatic pressure increases, this increased pressure tends to oppose further capillary filtration. Therefore, as long as the interstitial fluid hydrostatic pressure is in the negative pressure range, small increases in interstitial fluid volume cause relatively large increases in interstitial fluid hydrostatic pressure, opposing further filtration of fluid into the tissues.

As such, the interstitial fluid hydrostatic pressure must increase by about 3 mm Hg before large amounts of fluid will accumulate. However, in the positive pressure range, this safety factor against edema is lost b/c of the large increase in compliance of the tissues.

178. What is the importance of interstitial gel in preventing fluid accumulation in
the interstitium?
In normal tissues with negative interstitial fluid pressure, virtually all the fluid in the interstitium is in gel form.That is, the fluid is bound in a proteoglycan meshwork so that there are virtually no “free” fluid spaces larger than a few hundredths of a micrometer in diameter. The importance of the gel is that it prevents fluid from flowing easily through the tissues because of impediment from the “brush pile” of trillions of proteoglycan filaments.

Also, the compliance of the tissues is very low in the negative pressure range.
179. What happens when interstitial fluid pressure rises to the positive pressure range?
There is a tremendous accumulation of free fluid in the tissues.

In this pressure range, the tissues are compliant, allowing large amts of fluid to accumulate w/relatively small additional increases in interstitial fluid hydrostatic pressure.

When this occurs, the edema is said to be pitting edema b/c one can press the thumb against the tissue area and push the fluid out fo the area. (Different from non-pitting edema, which occurs when the tissue cells swell instead of the interstitium or when the fluid in the interstitium becomes clotted w/fibrinogen so that it cannot move freely within the tissue spaces).
180. What is the importance of the proteoglycan filaments in preventing rapid flow of fluid in the tissues?
The proteoglycan filaments, along with much larger collagen fibrils int eh interstitial spaces, acts as a "spacer" between the cells.

Nutrients and ions do not readily diffuse thru cell membranes; therefore, without adequate spacing between cells, there nutrients could not be rapidly exchanged between the blood capillaries and cells located at a distance from one other.

The proteoglycan filaments also prevent fluids from flowing too easily through the tissue spaces
181. How is increased lymph flow a safety factor against edema?
Lymph flow can increase 10-50x when fluid begins to accumulate in the tissues. This allows the lymphatics to carry away large amounts of fluid and proteins in response to increased capillary filtration, preventing the interstitial pressure from rising into the positive pressure range.

The safety factor caused by increased lymph flow has been calculated to be about 7 mm Hg.
182. How is washdown of the interstitial fluid protein a safety factor against edema?
Decreasing the interstitial fluid proteins lowers the net filtration force across the capillaries and tends to prevent further accumulation of fluid.

The safety factor from this effect has been calculated to be about 7 mm Hg.
183. What is the total safety factor against edema?
About 17 mm Hg.

This means that the capillary pressure in a peripheral tissue could rise by 17 mm Hg, or approx double the normal value, before marked edema would occur.
184. What is edema fluid in potential spaces called?

Thus, lymph blockage or any of the multiple abnormalities that can cause excessive capillary filtration can cause ffusion in the same way that interstitial edema is caused.

The abdominal cavity is especially prone to collect effusion fluid, called ascites.
185. Most common congenital defects
Atrial septal defects; represent 10 to 17% of cases with a higher prevalence in women (60%).
186. Atrial septal defects
ASD defects are classified according to their location in the interatrial septum.

Most common ASD (the ostium secundum defect) involves the fossa ovalis

Ostium primum defects (20%) involve the atrioventricular junction and are at one of the spectrum of AV septal defects
187. Ostium secundum defect
(60%) Involves the fossa ovalis

Left-to-right shunting of blood.
188. Ostium primun defects
(20%) involve the atrioventricular junction and are at one of the spectrum of AV septal defects.

Primum ASDs are usually associated with a cleft mitral valve and mitral regurgitation.

Left-to-right shunting of blood.

In rare cases, can also be associated w/a large VSD and a single AV valve, forming an AV septal defect.
189. Larger ASDs
If the defect is large, then the right atrium and right ventricle dilate to accommodate the increased volume of shunted blood.

Pressure in the pulmonary artery increases secondary to the increased volume of blood.
190. Signs of ASDs
1. A prominent right ventricular pulsation may be heard on physical exam along the left sternal border

2. A dilated hyperdynamic right ventricle

3. The S2 sound is widely split and fixed.

4. An ejection quality murmur that increases with inspiration is commonly heard at the left sternal border and is secondary to increased blood flow across the pulmonary valve.
191. Indications for ASD closures

1. Cardiac enlargement by chest XRay
2. Right ventricular enlargement by ECG
3. Elevation of pulmonary artery pressure
4. Defects greater than 8mm in diameter

Contraindication for closure:
Pulmonary hypertension
192. Ventricular septal defects
A common congenital abnormality in newborns and is present in approx 1/500 normal births.

Left-to-right shunting of blood

50% close spontaneously during childhood.

Most VSDs involve the membranous septum.

Less common types of VSD involve the AV canal, which is often associate w/ostium primum ASDs
193. Large VSDs
If the defect is large, the right ventricle dilate to accommodate blood flow increases.

If the condition is uncorrected, then pulmonary vascular obstruction may develop and lead to pulmonary artery hypertension
194. Signs of VSD
1. Hyperdynamic precordium

2. Palpable thrill along the left sternal border

3. Holosystolic left parasternal murmur

4. Right ventricular hypertrophy
195. Eisenmerger syndrome
The ES is characterized by elevated pulmonary vascular resistance and right-to-left shunting of blood through a systemic-to-pulmonary circulation connection such as PDA, VSD, ASD, and aorticopulmonary septal defect.

Not a candidate for surgical correction of VSD!
196. Signs of a congenital aortic stenosis or bicuspid aortic valve
1. Decreased carotid upstroke

2. Sustained apical impulse

3. Single S2, S4 sound

4. Systolic ejection murmur

5. Left ventricular hypertrophy (prominent on chest XR)
197. Subaortic stenosis
Often diagnosed in adulthood and is characterized by the presence of a discrete, fibrous diaphragm that encircles the left ventricular outflow tract btwn the mitral annulus and the basal IV septum

Patients w/this defect have a characteristic outflow murmur but not the systolic ejection click appreciated in patients w/bicuspid aortic valves.

Requires endocarditis prophlylaxis
198. Supravalvar aortic stenosis (SVAS)
SVAS is a rare form of outflow obstruction characterized by varying degrees of ascending aortic root stricture. Loss of function mutations in the ECM protein, elastin, are responsible for smooth muscle hypertrophy in SVAS.

Requires endocarditis prophlylaxis
199. Pulmonic valve stenosis
Most common cause of obstruction to right ventricular outflow and usually occurs as an isolated congenital lesion.

Fusion of the pulmonary leaflets creates the pressure overloaded state and results in right ventricular hypertrophy.

Requires endocarditis prophlylaxis; valve replacement is rarely necessary.
200. Signs of pulmonic valve stenosis
1. Right ventricular lift on palpation of the precordium

2. S1 sound is usually normal and is followed by an opening click that becomes louder w/expiration

3. P2 sound becomes softer and is delayed as the severity of the stenosis increases.

4. Systolic ejection murmur at left sternal border that increases w/inspiration
201. Ebstein's anomaly
A rare condition characterized by apical displacement of the tricuspid valve into the right ventricle.

As a result, the basal portion of the right ventricle forms part of the right atrium and leaves a small function right ventricle.

A patent formamen ovale or ostium secundum ASD is present in more than 50% of cases and may result in right-to-left shunt flow as right atrial pressure increases.
202. Signs of Ebstein's anomaly
1. Acyanotic or cyanotic
2. Increased jugular venous pressure
3. Prominent v wave
4. Systolic murmur at sternal border, increases w/inspiration
5. Right atrium abnormality (enlarged)
6. Right bundle branch block
203. Coarctation of the aorta
A fibrotic narrowing of the aortic lumen usually located distal to the left subclavian artery in the region of the ligamentum arteriosus.

Produces obstruction to left ventricular outflow and results in a rise in blood pressure int he proximal aorta and great vessels relative to the distal aorta and lower extremities
204. Signs of coarctation of aorta
1. Delayed femoral pulses
2. Reduced blood pressure in lower extremities
3. Findings associated w/bicuspid aortic valve
4. Left ventricular hypertrophy
5. Post stenotic aortic dilation
6. Prominent ascending aorta
205. Can a coarctation of aorta be left untreated?
More than two thirds of patients will develop left ventricular dysfunction and congestive heart failure by the fourth decade of life if left untreated.
206. Patent ductus arteriosus (PDA)
A persistent communication between the aorta and pulmonary artery is the result of the failure of the ductus arteriosus to close.

Closure is indicated in all cases except in those patients with silent PDAs and in those with large PDAs associated w/severe, irreversible pulmonary vascular disease
207. Large PDA defect
If the defect is large, blood flow thru the pulmonary circulation returning to the left side of the heart is significantly increased, resulting in left ventricular volume overload and pulmonary congestion.
208. Signs of PDA defect
1. Hyperdynamic apical impulse
2. Continuous machinery-like murmur
3. Left ventricular hypertrophy
4. Prominent pulmonary artery
5. Enlarged LA and LV
209. Signs of an Eisenmerger PDA
Characterized by:

1. Loss of the continuous murmur

2. Signs of pulmonary hypertension

3. Differential cyanosis and clubbing
210. Tetralogy of Fallot
Tetralogy is the result of a malalignment of the aorticopulmonary septum that divides the truncus arteriosus into the aorta and pulmonary artery during development, resulting in deviation of the aorta anteriorly towards the pulmonary artery

Results in right-to-left shunting of blood
211. Four characteristics of Tetralogy
1. Overriding of the aorta in relation to the ventricular septum
2. Pulmonary stenosis (due to right ventricular outflow obstruction)
3. Membranous VSD
4. Right ventricular hypertrophy
212. Signs of Tetralogy of Fallot
1. Usually cyanotic
2. Possible clubbing
3. Prominent ejection murmur at left sternal border
4. Soft or absent P2
5. RV hypertrophy
6. RA abnormality
7. Boot shaped heart
8. Small pulmonary artery
213. Complete transposition of the great arteries
AKA D-transposition

Most common cyanotic congenital heart disease.

Characterized by abnormal ventriculoarterial connections w/the aorta arising from the right ventricle and the pulmonary artery arising from the left.

Can support fetal development, but serious consequences result on closure of the foramen ovale and ductus arteriosus shortly after birth.
214. Corrected transposition of the great arteries
AKA L-transposition

Inversion of the ventricles and abnormal positioning of the great arteries characterize congenital-corrected transposition of the great arteries (L-transposition).

The anatomic right ventricle lies on the left and receives oxygenated blood from the left atrium. Blood is ejected into an anteriorly displaced aorta. The anatomic left ventricle lies on the right and receives venous blood from the right atrium and ejects it into the posteriorly displaced pulmonary artery.
215. Single ventricle
Tricuspid atresia, double-inlet left ventricle w/VSD, and large atrioventriclular septal defect may all have similar consequences to the patient.

The cardiac output is directed in common to both the aorta and the pulmonary artery, w/the balance between the two circulatory beds determined by the degree of outflow tract obstruction.
216. What is the Fontan procedure?
Goal is to optimize pulmonary blood flow w/o volume loading the ventricle.

The Fontan procedure and its modifications connect all systemic venous return to the pulmonary artery w/o an intervening ventricular pump.

Effectively separates the two circulation and provides relief of cyanosis w/o providing a volume load on the left ventricle on a pressure load on the pulmonary arteries.
217. Role of blood in the body
1. Transport of nutrients and oxygen directly to cells

2. Transport of wastes and carbon dioxide away from cells

3. Delivery of hormones and other regulatory substances to and from cells and tissues

4. Maintenance of hemostasis by acting as a buffer and by participating in coagulation and thermoregulation

5. Immune function
218. Hematocrit (HCT)
Percentage of the volume of cellular elements vs. total volume

39-50% in males

35-45% in females
219. What do blood cells and their derivatives include?
1. Erythrocytes, RBCs
2. Leukocytes, WBCs
3. Thrombocytes, platelets
220. Plasma
91-92% water

7-8% protein

1% electrolytes, nonprotein nitrogen substances, nutrients, blood gases, and regulatory substances
221. Albumin
Smallest plasma protein

Maintains colloid osmotic pressure

Is a carrier protein for hormones (thyroxine), metabolites (bilirubin), and drugs (barbituates)
222. γ-globulins vs. α- and β-globulins
γ-globulins are immunoglobulins, whereas α- and β-globulins are nonimmunoglobulins
223. α- and β-globulins
1. Secreted by the liver
2. Helps clot formation
3. Maintains colloid osmotic pressure
4. Carrier protein for:
-copper (coeruloplasmin)
-iron (transferrin)
-hemoglobin (haptoglobin)
224. Fibrinogen
Largest plasma protein secreted by the liver; involved in a series of cascade reactions with other coagulation factors.

Soluble fibrinogen is made into fibrin, which then rapidly polymerize to form long, insoluble fibers.

These fibers become cross-linked and form an impermeable net at the site of damaged blood vessels that prevents further blood loss.
225. Morphology of the erythrocyte
1. Anucleate eosinophilic cells devoid of typical organelles
2. Biconcave disc, 7.8 um
3. Extremely deformable
4. Binds oxygen and carbon dioxide
5. 120 days life span
6. Broken down in the spleen, bone marrow and live
226. What are the two major families of integral membrane proteins that maintain the shape of the RBC?
Two major families:

1. Glycophorins
-Glycophorin C plays an important role in attaching the underlying cytoskeletal protein network to the cell membrane

2. Band 3 protein
-binds hemoglobin and acts as an additional anchoring site for the cytoskeletal proteins
227. What are some of the peripheral membrane proteins that help maintain the shape of the RBC?
The lattice of the membrane is composed of :

1. Spectrin tetramers
2. Actin
3. Band 4.1
4. Adducin
5. Band 4.9
6. Tropomyosin
7. Ankyrin
8. Band 4.2

These are organized into a hexagonal lattice network.
228. Heriditary elliptocytosis is caused by...?

What does it result in?
Caused by a deficiency in band 4.1 protein that results in elliptic erythrocytes.

Results in hemolysis
229. Role and structure of hemoglobin
1. Transport oxygen and carbon dioxide
2. Responsible for the eosinophilic staining of the RBC
3. Consists of 4 polypeptide subunits
4. Each subunit contains a heme
5. Four different types of globin chains, α,β,γ,δ bound in pairs
230. HbA
Most prevalent in adults, accounting for about 96% of the total Hb.

Consists of two α- and two β- chains
231. HbA2
Accounts for 1.5 - 3% of total Hb in adults.

Consists of two α- and two δ- chains
232. HbF
Accounts for less than 1% of total Hb in adults

Contains two α- and two γ- chains and is the prinicpal form of Hb in the fetus.

Although it persists in slightly higher percentages than normal in sickle cell disease and thalassemia, it does not appear to have a pathologic role.
233. Cause of sickle cell anemia
Caused by a single point mutation in the gene that encodes the β- globin chain of HbA.

Valine is substituted with glutamic acid in position 6
234. Neutrophils
Named after the lack of the characteristic cytoplasmatic staining

-Multilobed nucleus (usually tri-lobed)
-Heterochromatin in periphery of nucleus
-Euchromatin in the middle of nucleus
-Barr bodies in females

Granules are small, barely visible

Small golgi apparatus and few mitochondria
235. Neutrophil granules
1. Azurophylic granules 1˚
-Larger granules, more numerous
-Lysosomes containing myeloperoxydase that generates bactericidal hypochlorite
-Cationic proteins called defensins which also have bactericidal properties

2. Specific granules 2˚
-Smallest granules, most numerous
i. Enzymes (type IV collagenase, phospholipidase)
ii. Complement activators
iii. Bactericidal agent (lysosyme)

Tertiary granules 3˚
Two types:
i. Phosphatase containing
ii. Metalloproteinase (gelatinase and collagenase) containing which facilitate migration of neutrophils thru the connective tissue.
236. Important property of neutrophils
Their motility.

They are the most numerous of the first wave of cells to enter an area of tissue damage.

Their migration is controlled by the expression of adhesion molecules on the neutrophil surface that interact w/the corresponding ligands on endothelial cells.
237. Migration of neutrophils to injury site
1. Selectins interact w/selectin receptor on the endothelium
2. Integrins are activated by chemokine signals of the endothelium
3. Integrins and immunoglobulins on the neutrophils bind to their receptors on the endothelium
4. Mast cells release histamine and heparin that opens a gap on the capillary
5. Neutrophil migrates in to the connective tissue
6. Further migration is directed by chemoattractant molecules to the injury site - chemotaxis.
238. Neutrophil phagocytosis
1. Fc receptors recognize the antibodies coating the antigen
2. Antigen is engulfed by the neutrophil
3. Phagosome is formed, digestion is started by oxidases
4. Specific and azurophilic granules fuse with phagosome (degranulation)
5. Digestion is completed by the enzymes
6. Digested material is either exocytosed or stored w/in the cell as a residual body
239. Eosinophils
Names after the large eosinophilic granules in the cytoplasm.

-Typically bilobed
-Herterchromatin in the periphery of the nucleus
-Euchromatin in the middle of the nucleus

Small golgi apparatus
Few mitochondria
240. Eosinophil granules
Specific granules:
1. Crystalloid body
-Major basic protein, cytotoxic to protozoans and helmintic parasites
2. Granule matrix
i. eosinophil cationic protein
ii. eosinophil peroxydase
iii. eosinophil derived neurotoxin - causes nervous system dysfunction in parasites
iv. *Histaminase - neutralizes histamine
v. Arylsulfatase
vi. Collagenase
vii. Cathepsins

Azurophylic granules
-lysosomes containing hydrolytic enzymes
241. Basophils
Names after the large basophilic granules in the cytoplasm

Closely related to mast cells of the connective tissue

-Typically bilobed nucleus obscured by the granules
-Heterochromatin in the periphery
-Euchromatin in the middle

Small golgi apparatus
Few mitochrondria
242. Basophil granules
Specific granules: grainy texture
-*Heparan sulfate; responsible for basophilia
-*Histamine; vasodilation
-*SRS-A; slow reacting substance A; vasodilation

Azurophylic granules
-lysosomes containing acid hydrolases
243. Basophil plasma membranes contain what immunoglobulins/cytokines?
1. Possesses Fc receptors for IgE
-IgE triggers the release of substances from the granules

2. Expresses CD40L protein that interacts w/the complementary receptor on the B lymphocytes; this increases IgE synthesis
244. B-lymphocytes
1. 20-30% of lymphocytes

2. Matures in the bone marrow

3. Variable life span, involved in production of circulating antibodies

4. Mature B cells express IgM, IgD, and MHC-II molecules

5. Express CD9, CD19, CD20, and CD24 marker proteins on their surface
245. T-lymphocytes
1.Differentiate and mature in the thymus

2. Long life span, involved in cell mediated immunity

3. Express CD2, CD3, CD7 marker proteins on their surface

4. DO NOT express antibodies on the cell surface

5. Subclassified on the basis of the presence of CD4 and CD8 proteins

6. 60-80% of lymphocytes
246. Subclassifications of T-lymphocytes
1. Cytotoxic CD8+ lymphocytes
2. Helper CD4+ lymphocytes
3. Suppressor CD8+, CD45RA+ lymphocytes
247. Cytotoxic CD8+ lymphocytes
1. Primary effector in cell mediated immunity
2. Recognize antigen-bound MHC-I molecules on virus infected and neoplastic cells
3. Secretes lymphokines and perforins that produce ion channels in the infected cell membrane leading to its lysis
4. Play role in rejection of allografts and in tumor immunology
248. Helper CD4+ lymphocytes
1. Recognize antigen-bound MHC-II molecules on antigen presenting cells
2. Activated helper cell produces interleukins stimulating proliferation and differentiation of more CD4+ cells
3. Newly differentiated cells secrete lymphokines that affect differentiation of B cells, T cells, and NK cells and turn B cells into plasma cells
249. Natural killer cells (NK cells)
1. 5-10% of lymphocytes
2. Programmed to kill certain virus infected cells and tumor cells
3. Larger than T and B cells
4. Kidney shaped nucleus, several large cytoplasmic granules
5. Express CD16, CD56, CD94 marker proteins on their surface
250. Suppressor CD8+, CD45A+ lymphocytes
1. Suppress antibody formation by B cells
2. Suppress the ability of T cells to initiate the immune response
3. May also regulate the erythroid cell maturation of the bone marrow.
251. Monocytes
1. Largest of leukocytes
2. Travel from bone marrow to the body tissues where they differentiate into various tissue macrophages
3. Phagocytize and degrade antigens, presenting their fragments on MCH II molecules sitting on the cell surface to helper CD4+ lymphocytes for recognition
4. Remain in the blood for only 3 days
5. Nucleus is bean (embryo) shaped
6. Cytoplasm contains small mitochondria, sER, rER, and small azurophillic granules.
252. Four zones of platelet structure: from outside to inside
1. Peripheral zone
2. Structural zone
3. Organelle zone
4. Membrane zone
253. Peripheral and structural zones of platelets
Peripheral zone:
Cell membrane covered by glycocalyx

Structural zone:
1. Microtubules
2. Actin filaments
3. Myosin
4. Actin-binding proteins supporting the plasma membrane (disc shape)
254. Organelle zone of platelets
1. Mitochondria
2. Peroxisomes
3. Glycogen particles
4. α-, *δ-, **λ-granules

*δ-granules contain ADP, ATP, serotonin, and histamine which facilitate platelet adhesion and vasoconstriction

**λ-granules contain several hydrolytic enzymes similar to lysosomes which help function in clot resorption during later stages of vessel repair
255. Membrane zone of platelets
Open canalicular system (remnant of demarcation zones)

Dense tubular system (storage of calcium ions)
256. What are the six stages of erythrocytic differentiation?
1. Proerythroblast
2. Basophilic erythroblast
3. Polychormatophillic erythroblast
4. Orthochromatophillic erythroblast (normoblast)
5. Polychromatophillic erythroblast (reticulocyte)
6. Erythrocyte
257. Which stage of erythrocytic differentiation has a small, compact, densely stained nucleus?
The orthochromatophilic erythroblast (normoblast)

No longer capable of division at this stage
258. Which stage of erythrocytic differentiation has a large spherical nucleus w/one or two visible nucleoi?
259. Which stage of erythrocytic differentiation has extruded its nucleus?
The polychromatophilic erythrocyte (reticulocyte)

Constitute about 1-2% of the total erythrocyte count.
260. Which three stages of erythrocytic differentiation have mitotic division?
1. Proerythroblasts
2. Basophilic erythroblasts
3. Polychromatophilic erythroblasts
261. Band cells
In the neutrophil line, the band cell precedes development of the first distinct nuclear lobs.

The nucleus of the band cell is elongated and of nearly uniform width, giving it a horseshoe like appearance.

The % of band cells in the circulation is almost always low, however, they may increase in acute or chronic inflammation
262. What are the four developmental stages of granulocytes?
1. Myeloblasts
2. Promeylocytes
3. Myelocytes
4. Metamyelocytes
263. Which type of immature granulocytes are the only ones to produce aurophilic granules?
264. Which type of immature granulocytes are the first to exhibit specific granules?
265. Which type of immature granulocytes clearly exhibit their lines of differentiation as well as numerous specific granules?
The metamyelocyte is the stage at which neutrophil, eosinophil, and basophil lines can be clearly identified by the presence of numerous specific granules
266. Normocellular bone marrow
The number of hemopoietic cells decreases with age.

Bone marrow with a normal age-specific index is called normocellular bone marrow
267. Hypocellular bone marrow
Occurs in aplastic anemia or after chemo

Only a small number of blood forming cells can be found in a marrow biopsy.
268. Hypercellular bone marrow
Characteristic of bone marrow affect by tumors originating from hematopoietic cells.
269. Red bone marrow
Active bone marrow

The cords of hemopoietic cells contain predominantly developing blood cells and megakaryocytes.

The cords also contain macrophages, mast cells, and some adipose tissue.
270. Yellow bone marrow
Inactive bone marrow - contains predominantly adipose tissue.

It is the chief form of bone marrow in the medullary cavity of bones in the adult that are no longer active, such as the long bones of the arms, legs, fingers, and toes
271. What is the normal weight of the heart?
It averages approx 250-300 g in females and 300-350 g in males.
272. What are the five major components of the cardiac myocytes?
1. Cell membrane (sarcolemma) and T-tubules, for impulse conduction
2. Sarcoplasmic reticulum, a calcium reservoir needed for contraction
3. Contractile elements
4. Mitochondria
5. Nucleus
273. What does a sarcomere consist of?
Sarcomeres are an orderly arrangement of thick filaments composed principally of myosin and thin filaments containing actin.

They also contain the regulatory proteins troponin and tropomyosin.
274. Myocytes comprise what percentage of the cells in the heart?
Approx 25%.

However, b/c cardiac myocytes are so much larger than the intervening cells, they account for more than 90% of the volume of the myocardium.
275. How do atrial myocytes differ from ventricular myocytes?
Atrial myocytes are smaller in diameter and less structured. Some atrial cells also differ in having distinctive electron dense granules in the cytoplasm called specific atrial granules. They are the sites of storage of atrial natriuretic peptide (ANP).
276. What is ANP?
ANP is a polypeptide secreted into the blood under conditions of atrial distention. ANP can produce a variety of physiologic effects, including vasodilation, natriuresis, and diuresis, actions beneficial in pathologic states such as hypertension and congestive heart failure.
277. What are intercalated disks?
These unique cardiac muscle cells join individual cells and within specialized intercellular junctions permit both mechanical and electrical (ionic) coupling.

They have gap junctions, which facilitate synchronous myocyte contraction.
278. What are the four specialized conduction components of the heart?
1. SA node
2. AV node
3. Bundle of His
4. Right and left bundle branches
279. What are the three major coronary arteries?
1. LAD
2. LCX
3. RCA
280. What does the LAD supply?
LAD supplies:

1. Most of the apex of the heart
2. The anterior wall of the left ventricle
3. The anterior 2/3's of the ventricular septum
281. What does the RCA supply?
In right dominant circulation, it perfuses:

1. Entire right ventricular free wall
2. Posterior wall of the left ventricle
3. Posterior 1/3rd of the ventricular septum
282. What does the LCX supply?
In right dominant circulation, it generally perfuses only the lateral wall of the left ventricle.
283. What is the nodule of Arantius?
Each aortic cusp has a small nodule (nodule of Arantius) in the center of the free edge, which facilitates closure.
284. What are the effects of aging on the heart?
1. Chambers
a. increased left atrial size
b. decreased left ventricle size
c. sigmoid-shaped ventricular septum

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

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

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

5. Aorta
a. dilated ascending aorta w/rightward shift
b. elongated and tortuous thoracic aorta
c. elastic fragmentation and collagen accumulation
d. atherosclerotic plaque
285. What are the five principal mechanisms by which cardiovascular dysfunctions occur?
1. Failure of the pump
2. Blood flow obstruction
3. Regurgitant flow
4. Disorders of cardiac conduction
5. Disruption of the continuity of the circulatory system, or shunts
286. What is the contemporary view of the cause of cardiovascular diseases?
Most clinical cardiovascular diseases result form a complex interplay of genetics and environmental factors that disrupt networks controlling morphogenesis, myocyte survival, biomechanical stress responses, contractility, and electrical conduction.
287. What is CHF?
Congestive heart failure is the common end point of many forms of heart disease.

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

CHF is characterized by diminished cardiac output, accumulation of blood in the venous system, or both.
287. What are the three main mechanisms by which the cardiovascular system maintains arterial pressure?
1. Frank-Starling mechanism
2. Hypertrophy, w/ or w/o cardiac chamber dilation
3. Activation of the neurohumoral systems
-Atrial natriuretic peptide
288. What are most instances of heart failure from?
Most instances of heart failure are the consequence of progressive deterioration of myocardial contractile function (systolic dysfunction)
289. When does diastolic dysfunction occur?
Occasionally, failure results from inability of the heart chambers to relax sufficiently during diastole so that the ventricles can properly fill.

This can occur with massive left ventricular hypertrophy, myocardial fibrosis, deposition of amyloid, or constrictive pericarditis.
290. What are the three compensatory mechanisms in response to CHF?
1. Ventricular dilation
2. Blood volume expansion by salt and water retention
3. Tachycardia

Unfortunately, these changes ultimately impose further burdens on cardiac function.
291. What are the early mediators of hypertrophy?
c-fos, c-myc, c-jun, and ERG1.

Selective up-regulation or re-expression of embryonic/fetal forms of contractile and other proteins also occurs.
292. Cardiac hypertrophy summary
The geometry, structure, and composition of the hypertrophied heart are not normal. Cardiac hypertrophy constitutes a tenuous balance between adaptive characteristics and potentially deleterious structural and biochemical/molecular alterations, (including decreased capillary-to-myocyte ratio, increased fibrous tissue, and synthesis of abnormal proteins).

Thus, sustained cardiac hypertrophy often evolves to cardiac failure.
293. What are the most common causes of left-sided heart failure?
1. ischemic heart disease
2. hypertension
3. aortic and mitral valvular disease
4. nonischemic myocardial disease

The clinical effects of left-sided CHF primarily result from progressive damming of blood within the pulmonary circulation and the consequences of diminished peripheral blood pressure and flow.
294. Morphology of left-sided heart failure (three main manifestations)
1. Classically, pulmonary congestion and edema due to impaired pulmonary outflow
2. Reduced renal perfusion (due to diminished CO), causing salt and water retention, ischemic acute tubular necrosis, and impaired waste excretion, causing prerenal azotemia.
3. Reduced central nervous system perfusion, often causing hypoxic encephalopathy, with symptoms ranging from irritability to coma.
295. What is right sided heart failure?
Right sided heart failure is most commonly caused by left-sided failure. Pure right-sided heart failure can be caused by tricuspid or pulmonary valvular disease, or by intrinsic pulmonary or pulmonary vasculature disease causing functional, right ventricular outflow.
296. Pure right sided heart failure most often occurs w/what?
Pure right sided heart failure most often occurs w/chronic severe pulmonary hypertension and thus is called cor pulmonale.

In this condition, the right ventricle is burdened by a pressure workload due to increased resistance w/in the pulmonary circulation.
297. What are the four major manifestations of right-sided heart failure?
1. Portal, systemic, and dependent peripheral congestion and edema (anasarca), with effusions
2. Hepatomegaly with centrilobular congestion and atrophy of central hepatocytes, producing a nutmeg appearance.
3. Congestive splenomegaly with sinusoidal dilation, focal hemorrhages, hemosiderin deposits, and fibrosis
4. Renal congestion, hypoxic injury, and ATN (more marked in right vs. left sided CHF)
298. Centrilobular necrosis in the liver can lead to...?
With long standing right sided CHF, the central areas can become fibrotic, creating so-called cardiac sclerosis or cardiac cirrhosis.
299. How do the symptoms of left sided CHF differ from right sided CHF?
The symptoms of pure left-sided HF are largely due to pulmonary congestion and edema.

In contrast, in right-sided HF, respiratory symptoms may be absent or insignificant, and there is a systemic and portal venous congestive syndrome, with hepatic and splenic enlargement, peripheral edema, pleural effusion, and ascites.
300. What is congenital heart disease?
Congenital heart disease is a general term used to describe abnormalities of the heart or great vessels that are present from birth; most are attributable to faulty embryogenesis during gestational weeks 3-8, when major cardiovascular structures develop.

The most severe anomalies may be incompatible with intrauterine survival; defects that permit embryologic maturation and birth generally involve only specific chambers or regions of the heart, while the remainder of the heart develops normally.
301. What is the role of genetic factors in congenital heart disease?
Well defined genetic causes are only identifiable in (10%) of cases.

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

A congenital heart defect in a parent or preceding sibling is the greatest risk factor for developing a cardiac malformation.
302. What infections can lead to congenital heart disease?
Congenital rubella infection
303. Mutations of what genes cause the ASD and VSD observed in the Holt-Oram syndrome?
Mutation of the gene that encodes the transcription factor, TBX5, has been shown to cause the ASD and VSD observed in the Holt-Oram syndrome.
304. What is NKX2.5?
The gene encoding fo rthe transcription factor NKX2.5 causes nonsyndromic (isolated) ASD in humans when one copy is missing.

This gene is the the human counterpart of the tinman gene of the fruit fly, b/c fruit fly embryos lacking both copies of tinman have no hearts.
205. The wide range of anomalies of the outflow tract are caused by what?
Developmental errors in mesenchymal tissue migration.

Outflow tract defects may be caused by the abnormal development of neural crest derived cells, whose migration into the embryonic heart is required for formation of the outflow tracts of the heart?
206. What chromosome is associated with the (ab)normal development of the conotruncus, branchial arches, and the face?
Chromosome 22q11.2 deletions are seen in 15-50% of these disorders.
207. What are other common mechanisms of congenital heart disease?
1. ECM abnormalities
2. Situs and looping defects
208. What are the clinical features of congenital anomalies of the heart?
They not only have direct hemodynamic sequelae, but also have cyanosis, retarded development, and failure to thrive.

They are at increased risk of chronic or recurrent illness and of infective endocarditis (due to abnormal valves or endocardial injury from jet lesions).
209. What are left-to-right shunts?

When are they not surgically correctable?
Left-to-right shunts induce chronic right-sided volume overload with secondary pulmonary hypertension and right ventricle hypertrophy; eventually, right sided pressured exceed left sided pressures, and the shunt becomes right to left.

Hence, cyanosis appears late.

Once significant pulmonary hypertension develops, the underlying structural defects are no longer candidates for surgical correction.
210. What are the three major left-to-right shunts?
1. ASD
2. VSD
3. PDA
211. What are ASDs?
An ASD is an abnormal opening in the atrial septum that allows communication of blood between the left and right atria.

ASD is the most common congenital cardiac anomaly seen in adults. It is usually asymptomatic until adulthood.
212. What are the three types of ASDs?
1. Primum type: only 5% of ASDs, but common in Down syndrome, this type occurs low in the atrial septum, and occasionally is associated with mitral valve deformities

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

3. Situs venosus type: 5% of ASDs; this type occurs high in the septum near the SVC entrance. It can be associated w/anomalous right pulmonary vein drainage into the SVC or right atrium.
213. Morphology of ASDs
ASDs result in a left-to-right shunt, largely b/c pulmonary vascular resistance is considerably less than systemic vascular resistance and b/c the compliance of the right ventricle is much greater than that of the left.

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

Eventually, volume hypertrophy of the right atrium and right ventricle develops.
214. Why do ASDs become symptomatic after age 30?
In adulthood, either right sided heart failure occurs or gradually increasing right-sided hypertrophy and pulmonary hypertension finally induce right-to-let shunting w/cyanosis.

Early surgical correction is advocated to prevent pulmonary vascular changes.
215. What are VSDs?
Incomplete closure of the ventricular septum, allowing free communication and thus a shunt from left to right ventricles.

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

Depending on the size of the defect, it may produce difficulties virtually from birth or, with smaller lesions, may not be recognized until later or may even spontaneously close.
216. What are the classifications of the VSDs?
Most are about the size of the aortic valve orifice. About 90% involve the region of the membranous septum (membranous VSD).

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

Although most often single, VSDs in the muscular septum may be multiple.
217. With moderate-sized VSDs, patients are at increased risk of what...?
Infective endocarditis
218. Clinical course of VSDs
Depending on the VSD size, the clincical picture ranges from fulminant CHF to late cyanosis, to asymptomatic holosystolic murmurs, to spontaneous closure (50% of those <0.5 cm diameter).

Surgical correction is desirable before right-sided heart overload and pulmonary hypertension develop.
219. What is a PDA?
At birth, under the influence of higher oxygen tensions and reduced local prostaglandin E synthesis, muscular contraction normally closes the ductus within 1 or 2 days of life. Persistence patency beyond that point is generally permanent.

About 85-90% of PDA occur as isolated defects,. Left ventricular hypertrophy and pulmonary artery dilation occur secondary to ductus patency.
220. Consequences of PDA
Although initially asymptomatic (but notable for a prominent machinery-like heart murmur), long standing PDA causes pulmonary hypertension followed by right ventricle hypertrophy and eventually right to left shunting with late cyanosis.

Early PDA closure (either surgically or with prostaglandin synthesis inhibitors) is advocated.
221. What are right-to-left shunts?

What are the primary and secondary findings in these shunts?
Right-to-left shutns (cyanotic congenital heart disease) cause cyanosis from the outset by allowing poorly oxygenated blood to flow directly into the systemic circulation (they also permit paradoxical embolism).

Secondary findings include:
1. Fingers and toe clubbing
2. Hypertrophic osteoarthropathy
3. Polycythemia
222. What are the three major congenital right-to-left shunts?
1. Tetralogy of Fallot
2. Transposition of the great arteries
3. Truncus arteriosus
223. What is Tetralogy of Fallot?
Owing to anterosuperior displacement of the infundibular sptum, the cardinal finding are:

1. VSD
2. Overriding aorta
3. Pulmonary stenosis w/right ventricle outflow obstruction
4. Right ventricular hypertrophy
224. Clinical course of Tetralogy
Symptom severity is directly related to the extent of right ventricle outflow obstruction.

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

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

Surgical correction can be delayed provided that the child can tolerate the level of oxygenation; when present, pulmonary valvular stenosis protects the lung form volume and pressure overload, and right ventricular failure is rare b/c it can pump excess volume into the left ventricle and aorta.
225. What is the shape of the heart in Tetralogy?
The heart is often "boot shaped" owing to marked right ventricular hypertrophy, particularly of the apical region.
226. What is transposition of the great arteries (TGA)?
Transposition of the great arteries means the aorta arise from the right ventricle and the pulmonary artery emanates from the left ventricle.

The AV connections are normal, with right atrium joining right ventricle and left atrium emptying into the left ventricle.
227. What is the essential embryologic defect in complete TGA?
Abnormal formation of the truncal and aortopulmonary septa.

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

The result is separation of the systemic and pulmonary circulations, a condition incompatible with postnatal life unless a shunt exists for adequate mixing of blood.
228. What is the clinical course of TGA?
1. Right-to-left-shunting causes early cyanosis
2. Eventually the flow reverses, and patients develop right ventricle hypertrophy and pulmonary hypertension. The anomaly carries a poor prognosis.
229. What is a persistent truncus arteriosus?
The persistent truncus arteriosus arises from a developmental failure of separation of the embryologic truncus arterious into the aorta and pulmonary artery. This results in a single great artery that receives blood from both ventricles, accompanied by an underlying VSD, and this gives rise to the systemic, pulmonary, and coronary circulations.

B/c blood from the right and left ventricle mixes, there is early systemic cyanosis as well as increased pulmonary blood flow, with the danger of irreversible pulmonary hypertension.
230. What is tricuspid atresia?
Complete occlusion of the tricuspid valve orifice is known as tricuspid atresia.

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

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

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

A VSD is also present and affords communication between the left ventricle and the great artery that arises form the hypoplastic right ventricle. Cyanosis is present virtually from birth, and there is a high mortality in the first weeks or months of life.
331. What is a total anomalous pulmonary venous connection (TAPVC)?
TAPVC, in which no pulmonary veins directly join the left atrium, results embryologically when the common pulmonary vein fails to develop or becomes atretic, causing primitive systemic venous channels from the lungs to remain patent.

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

Either a patent foramen ovale or an ASD is always present, allowing pulmonary venous blood to enter the left atrium.
332. What are the consequences of TAPVC?
The consequences of TAPVC include volume and pressure hypertrophy of the right atrium and right ventricle, and these chambers and the pulmonary trunk are dilated.

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

Cyanosis may be present, owing to mixing of well-oxygenated and poorly oxygenated blood at the site of anomalous pulmonary venous connection and a large right-to-left shunt at the ASD.
333. What are the two classic forms of coarctation of the aorta?
1. An infantile form with tubular hypoplasia of the aortic arch proximal to a PDA that is often symptomatic in early childhood

2. And adult form in which there is a discrete ridge-like infolding of the aorta, just opposite the closed ductus arteriosus distal to the arch vessels.
334. What are some common defects that accompany coarctation of the aorta?
Although coarctation may arise as a solitary defect, it is accompanied by a bicuspid aortic valve in 50% of cases and may also be associated w/congenital aortic stenosis, ASD, VSD, mitral regurgitation, and berry aneurysms of the circle of Willis.
335. Coarctation with a PDA
Usually leads to manifestations early in life; indeed, it may cause signs and symptoms immediately after birth. Many infants w/this anomaly do not survive the neonatal period without surgical or catheter-based intervention.

In such cases, the delivery of unsaturated blood through the ductus arteriosus produces cyanosis localized to the lower half of the body.
336. Coarctation w/o a PDA
Most of the children are asymptomatic, and the disease may go unrecognized until well into adult life.

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

Particularly characteristic in adults is the development of collateral circulation between the precoarctation arterial branches and the postcoarctation arteries through enlarged intercostal and internal mammary arteries and the "rib notching".
337. What are some common symptoms in all coarctations?

How is it treated surgically?
With all significant coarctations, murmurs are often present throughout systole.

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

With uncomplicated coarctation of the aorta, surgical resection and end-to-end anastomosis or replacement of the affected aortic segment by a prosthetic graft yields excellent results.
338. What is pulmonary stenosis and atresia?
This relatively frequent malformation constitutes an obstruction at the pulmonary valve, which may be mild to severe.

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

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

When the valve is entirely atretic, there is no communication between the right ventricle and lungs, and so the anomaly is commonly associated with a hypoplastic right ventricle and an ASD; flow enters the lungs through a PDA.
339. Clinical course of pulmonary stenosis
Mild stenosis may be asymptomatic and compatible with long life. The smaller the valvular orifice, the more severe is the cyanosis and the earlier its appearance.
340. What are the three types of aortic stenosis?
1. Valvular aortic stenosis
2. Subaortic stenosis
3. Supravalvular aortic stenosis
341. What is valvular aortic stenosis?
The cusps may be hypoplastic, dysplastic (thickened, nodular), or abnormal in number.

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

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

The ductus may be open to allow blood flow to the aorta and coronary arteries. This constellation of findings, called the hypoplastic left heart syndrome, is nearly always fatal in the first week of life, when the ductus closes.
342. What is subaortic stenosis?
Subaortic stenosis represent either a thickened ring or collar of dense endocardial fibrous tissue below the level of the cusps.
343. What is supravalvular aortic stenosis?
Supravalvular aortic stenosis represents an inherited form of aortic dysplasia in which the ascending aortic wall is greatly thickened, causing luminal constriction.

It may be related to a development disorder affecting multiple organ systems, including the vascular system, which includes hypercalcemia of infancy (Williams syndrome).
344. Mutations in which gene are responsible for supravalvular aortic stenosis?
Mutations in the elastin gene cause supravalvular aortic stenosis, probably via disruption of an important elastin-smooth muscle cell interactions in arterial morphogenesis.
345. What are the clinical features of aortic stenosis?
A prominent systolic murmur is usually detectable and sometimes a thrill, which does not distinguish the site of stenosis.

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

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