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88
PHYSIOLOGY CASES AND PROBLEMS
Case 16
Primary Pulmonary Hypertension:
Right Ventricular Failure
At the time of her death, Celia Lukas was a 38-year-old homemaker and mother of three children, 15, 14, and 12 years of age. She had an associate's degree in computer programming from
a community college, but had not worked outside the home since the birth of her first child.
Keeping house and driving the children to activities kept her very busy. To stay in shape, she
took aerobics classes at the local community center. The first sign that Celia was ill was vague:
she fatigued easily. However, within 6 months, Celia was short of breath (dyspnea), both at rest
and when she exercised, and she had swelling in her legs and feet. She made an appointment
to see her physician.
On physical examination, Celia's jugular veins were distended, her liver was enlarged
(hepatomegaly), and she had ascites in her peritoneal cavity and edema in her legs. A fourth heart
sound was audible over her right ventricle. The physician was very concerned and immediately
scheduled Celia for a chest x-ray, an electrocardiogram (ECG), and a cardiac catheterization.
The chest x-ray showed enlargement of the right ventricle and prominent pulmonary arteries. The ECG findings were consistent with right ventricular hypertrophy. The results of cardiac
catheterization are shown in Table 2-4.
TABLE 2-4
Results of Celia's Cardiac Catheterization
Pressure
Value
Mean pulmonary artery pressure
Right ventricular pressure
Right atrial pressure
Pulmonary capillary wedge pressure
35 mm Hg (normal, 15 mm Hg)
Increased
Increased
Normal
Consulting physicians in cardiology and pulmonology concluded that Celia had primary
pulmonary hypertension, a rare type of pulmonary hypertension that is caused by diffuse pathologic changes in the pulmonary arteries. These abnormalities lead to increased pulmonary vascular resistance and pulmonary hypertension, which causes right ventricular failure (cor
pulmonale). Celia was treated with vasodilator drugs, but they were not effective. Her name was
added to a list of patients awaiting a heart-lung transplant. However, she died of right heart failure before a transplant could be performed.
oj QUESTIONS
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1. Why did increased pulmonary vascular resistance cause an increase in pulmonary artery pressure (pulmonary hypertension)?
2. What values are needed to calculate pulmonary vascular resistance?
3. Discuss the concept of "afterload" of the ventricles. What is the afterload of the left ventricle?
What is the afterload of the right ventricle? What is the effect of increased afterload on stroke
volume, cardiac output, ejection fraction, and end-systolic volume? How did Celia's increased
pulmonary artery pressure lead to right ventricular failure?
CARDIOVASCULAR PHYSIOLOGY 89
4. In the context of Celia's right ventricular failure, explain the data from the cardiac catheterization.
5. Why does right ventricular failure cause right ventricular hypertrophy? (Hint: Use the law of
Laplace to answer this question.)
6. Increased systemic venous pressure and jugular vein distension are the sine qua non (defining
characteristics) of right ventricular failure. Why were Celia's jugular veins distended?
7. During what portion of the cardiac cycle is the fourth heart sound heard? What is the meaning of an audible fourth heart sound?
8. Why did right ventricular failure lead to edema on the systemic side of the circulation (e.g.,
ascites, edema in the legs)? Discuss the Starling forces involved. Would you expect pulmonary
edema to be present in right ventricular failure?
9. Celia very much wanted to attend a family reunion in Denver. Her physicians told her that the
trip was absolutely contraindicated because of Denver's high altitude. Why is ascent to high altitude so dangerous in a person with pulmonary hypertension? (Knowledge of pulmonary physiology is necessary to answer this question.)
10. The physician hoped that vasodilator drugs would improve Celia's condition. What was the
physician's reasoning?
90 PHYSIOLOGY CASES AND PROBLEMS
51
ANSWERS AND EXPLANATIONS
1. To explain why increased pulmonary vascular resistance (caused by intrinsic pathology
of the small pulmonary arteries) led to increased pulmonary artery pressure, it is necessary
to think about the relationship between pressure, flow, and resistance. Recall this relationship from Case 10: AP = blood flow x resistance. Mathematically, it is easy to see that if blood
flow (in this case, pulmonary blood flow) is constant and resistance of the blood vessels
increases, then AP, the pressure difference between the pulmonary artery and the pulmonary vein, must increase. AP could increase because pressure in the pulmonary artery
increases or because pressure in the pulmonary vein decreases. (Note, however, that a
decrease in pulmonary vein pressure would have little impact on AP because its value is normally very low.)
In Celia, AP increased because her pulmonary arterial pressure increased. As pulmonary vascular resistance increased, resistance to blood flow increased, and blood "backed up" proximal
to the pulmonary microcirculation into the pulmonary arteries. Increased blood volume in the
pulmonary arteries caused increased pressure.
2. Pulmonary vascular resistance is calculated by rearranging the equation for the pressure, flow,
resistance relationship. AP = blood flow x resistance; thus, resistance = AP/blood flow. AP is the
pressure difference between the pulmonary artery and the pulmonary vein. Pulmonary blood
flow is equal to the cardiac output of the right ventricle, which in the steady state, is equal to the
cardiac output of the left ventricle. Thus, the values needed to calculate pulmonary vascular resistance are: pulmonary artery pressure, pulmonary vein pressure (or left atrial pressure), and cardiac output.
3. Afterload of the ventricles is the pressure against which the ventricles must eject blood. Afterload of the left ventricle is aortic pressure. Afterload of the right ventricle is pulmonary
artery pressure. For blood to be ejected during systole, left ventricular pressure must increase
above aortic pressure, and right ventricular pressure must increase above pulmonary artery
pressure.
Celia's increased pulmonary artery pressure had a devastating effect on the function of her
right ventricle. Much more work was required to develop the pressure required to open the pulmonic valve and eject blood into the pulmonary artery. As a result, right ventricular stroke volume, cardiac output, and ejection fraction were decreased. Right ventricular end-systolic volume
was increased, as blood that should have been ejected into the pulmonary artery remained in the
right ventricle. (Celia had cor pulmonale, or right ventricular failure secondary to pulmonary
hypertension.)
4. Celia's cardiac catheterization showed that her pulmonary artery pressure was increased, her
right ventricular pressure and right atrial pressure were increased, and her pulmonary capillary wedge pressure was normal. The increased pulmonary artery pressure (the cause of Celia's
right ventricular failure) has already been discussed: pulmonary artery pressure increased secondary to increased pulmonary vascular resistance. Right ventricular pressure increased
because more blood than usual remained in the ventricle after systolic ejection. As right ventricular pressure increased, it was more difficult for blood to move from the right atrium to
the right ventricle; as a result, right atrial volume and pressure also increased. Pulmonary capillary wedge pressure (left atrial pressure) was normal, suggesting that there was no failure on
the left side of the heart.
5. Right ventricular failure led to right ventricular hypertrophy (evident from Celia's chest
x-ray and ECG) because her right ventricle was required to perform increased work against an
increased afterload. The right ventricular wall thickens (hypertrophies) as an adaptive mechanism for performing more work. This adaptive response is explained by the law of Laplace for
a sphere (a sphere being the approximate shape of the heart):
CARDIOVASCULAR PHYSIOLOGY 91
2HT
Pr
where
P = ventricular pressure
H = ventricular wall thickness (height)
T = wall tension
r = radius of the ventricle
Thus, ventricular pressure correlates directly with developed wall tension and wall thickness,
and inversely with radius. The thicker the ventricular wall, the greater the pressure that can be
developed at a given tension. Celia's right ventricle hypertrophied adaptively so that it could
develop the higher pressures required to eject blood against the increased pulmonary artery
pressure.
6. Celia's jugular veins were distended with blood because right ventricular failure caused blood
to back up into the right ventricle, and then into the right atrium and the systemic veins.
7. A fourth heart sound is not normally audible in adults. However, it may occur in ventricular
hypertrophy, where ventricular compliance is decreased. During filling of a less compliant
ventricle, blood flow produces noise (the fourth heart sound). Thus, when it is present, the
fourth heart sound is heard during atrial systole.
8. As already explained, right ventricular failure caused blood to back up into the systemic veins,
which increased systemic venous pressure. The Starling forces that determine fluid movement
across capillary walls can be used to explain why edema would form on the systemic side
of the circulation (e.g., ascites, edema in the legs) when systemic venous pressure is increased
(Figure 2-12).
P
It;
Interstitial fluid
Figure 2-12 Starling pressures across the capillary wall. P„ capillary hydrostatic pressure; P,, interstitial hydrostatic pressure; Tr„ capillary oncotic pressure; ir r , interstitial oncotic pressure.
There are four Starling pressures (or forces) across the capillary wall: capillary hydrostatic pressure (Pr ), capillary oncotic pressure (rr,), interstitial hydrostatic pressure (P,), and interstitial
oncotic pressure (rr,). As shown in Figure 2-12, P, and Tr, favor filtration of fluid out of the capillary, and IT, and P, favor absorption of fluid into the capillary. In most capillary beds, the Starling
pressures are such that there is a small net filtration of fluid that is returned to the circulation by
the lymphatics.
92 PHYSIOLOGY CASES AND PROBLEMS
Edema occurs when filtration of fluid increases and exceeds the capacity of the lymphatics
to return it to the circulation. The question, then, is why there was increased filtration of fluid
in Celia's case (assuming that her lymphatic function was normal). The answer lies in her
increased systemic venous pressure, which caused an increase in capillary hydrostatic pressure
(Pc ). Increases in P, favor filtration.
Pulmonary edema would not be expected to occur in right ventricular failure. Pulmonary
edema occurs in left ventricular failure, where blood backs up behind the left ventricle into the
left atrium and pulmonary veins. An increase in pulmonary venous pressure then leads to
increased pulmonary capillary hydrostatic pressure and increased filtration of fluid into the
pulmonary interstitium. Celia's left atrial pressure (estimated by pulmonary capillary wedge
pressure) was normal, suggesting that she did not have left ventricular failure; thus, pulmonary
venous pressure is not expected to have been elevated and pulmonary edema is not expected
to have occurred.
9. At high altitude, barometric pressure is decreased, resulting in decreased partial pressure of
atmospheric gases, such as 02 . If Celia had traveled to Denver, she would have breathed air
with a lower Pt,, than the air at sea level. Such alveolar hypoxia produces vasoconstriction in
the pulmonary circulation (normally a protective mechanism in the lungs that diverts blood
flow away from hypoxic areas). Celia's pulmonary vascular resistance was already abnormally
elevated as a result of her intrinsic disease. So-called hypoxic vasoconstriction at high altitude would have further increased her pulmonary vascular resistance and pulmonary arterial
pressure, and further increased the afterload on her right ventricle. (Incidentally, hypoxic vasoconstriction is unique to the lungs. Other vascular beds dilate in response to hypoxia.)
10. The physician hoped that vasodilator drugs would dilate pulmonary arterioles and decrease
Celia's pulmonary vascular resistance and pulmonary arterial pressure, thus lowering the afterload of the right ventricle.
R
ey topics
Afterload
Ascites
Cardiac catheterization
Cor pulmonale
Edema
Fourth heart sound
High altitude
Hypoxic vasoconstriction
Law of Laplace
Lymph, or lymphatic, vessels
Pulmonary capillary wedge pressure
Pulmonary edema
Pulmonary hypertension
Pulmonary vascular resistance
Right heart, or right ventricular, failure
Right ventricular hypertrophy
Starling forces, or pressures