Total blood volume.

Total blood volume (TBV) is a combination of plasma volume and RBC volume, each of which increases during pregnancy. Circulating blood volume increases begin by at least 6 weeks’ gestation.¹¹¹ Circulating blood volume increases by 30% to 40% (approximately 1½ L), with a usual range of 30% to 45%.^40,111,115 TBV increases rapidly until midpregnancy and then more slowly during the latter half, peaking at 28 to 34 weeks, then plateaus or decreases slightly to term.^{27,81,111,135} Changes in blood volume are due to the increased steroid hormones, plasma renin activity, aldosterone, human placental lactogen, atrial natriuretic factor, and other mediators.^18,48 Figure 8-1 illustrates changes in total blood volume and its component parts, plasma volume, and RBC volume.

The rise in blood volume correlates directly with fetal weight, supporting the concept of the placenta as an arteriovenous shunt in the maternal vascular compartment. Although the degree of hypervolemia varies from woman to woman, subsequent pregnancies in the same woman result in similar increases in circulating volume. Twin and other multiple pregnancies, however, result in greater increases in blood volume, imposing substantially greater demands on the cardiovascular system.^111,135

Plasma volume.

About 75% of the TBV increase is in plasma volume. Plasma volume increases progressively from 6 to 8 weeks by approximately 45% to 50% (range, 40% to 60%) or about 1200 to 1600 mL above nonpregnant values ^27,111 This change begins at 6 to 8 weeks and increases rapidly during the second trimester, followed by a slower but progressive increase that reaches its maximum of 4700 to 5200 mL at about 32 weeks.^22,81,111 Alterations in blood and plasma volume are influenced by hormonal effects, nitric oxide mediated vasodilation, mechanical factors (blood flow in uteroplacental vessels) (see Chapter 8), and changes in the renal system and in fluid and electrolyte homeostasis (see Chapter 11).

Nitric oxide mediated vasodilation induces changes in the renin-angiotensin-aldosterone system, with increased sodium and water retention (see Chapter 11).¹¹¹ Plasma renin activity and blood aldosterone levels are increased due to the action of estrogens, progesterone, and prostaglandins. An increase in plasma renin activity enhances sodium retention, thereby stimulating aldosterone secretion. Progesterone inhibits the action of aldosterone on the renal tubular cells, thus contributing to sodium retention and an increase in total body water. The degree of fluid retention is influenced by the increased distensibility of the vascular system and the uterine vein capacity present during pregnancy.²⁷

Fluid distribution changes depending on body position. For example, the standing position or prolonged sitting is associated with the development of dependent edema. This is probably due to the trapping of blood in the legs and pelvis as the gravid uterus creates a mechanical impedance to blood flow through the inferior vena cava. This causes an increase in venous pressure in the lower extremities and a sharp rise in hydrostatic pressure in the microcirculation, with subsequent leakage of fluid from the vascular bed into the interstitium. The result is edema of the feet and ankles. Venous distensibility contributes to the decreased venous return to the heart.¹¹²

Red blood cell volume.

Red blood cell (RBC) production and thus volume increases throughout pregnancy to a level 20% to 30% higher than nonpregnant values.^27,111 Intravascular expansion is mainly due to an increase in plasma volume; therefore hemodilution occurs. This physiologic anemia of pregnancy is reflected in a lower hematocrit and hemoglobin. These changes cannot be prevented with iron supplementation; however, women who are provided exogenous sources of iron do have higher hemoglobin levels in the third trimester than women not receiving supplements (see Figure 8-2). Changes in RBC volume are due to increased circulating erythropoietin and accelerated RBC production. The rise in erythropoietin in the last two trimesters is stimulated by progesterone, prolactin, and human placental lactogen.¹¹¹ Changes in RBC volume and the role of iron are described further in Chapter 8.

Cardiac output and stroke volume.

Cardiac output, which is the product of heart rate times stroke volume, is one of the most significant hemodynamic changes encountered during pregnancy. Fifty percent of the increase occurs by 8 weeks’ gestation, mediated by changes in SVR.^22,111 Cardiac output continues to rise more slowly until the third trimester to values, as measured in the left lateral recumbent position, 30% to 50% (usually 40% to 45%) greater than in nonpregnant women.^{1,18,25,27,111,115} A slight decline in cardiac output may be seen in late pregnancy due to the decrease in stroke volume near term.¹¹¹ The increase in cardiac output is associated with an increase in venous return and greater right ventricular (RV) output, especially in the left lateral position.¹⁵⁸

The increased cardiac output is due to changes in both stroke volume and heart rate. Changes in heart rate and stroke volume are reported by 5 weeks’ and 8 weeks’ gestation, respectively.¹¹¹ The rise in cardiac output early in pregnancy is due primarily to an increase in stroke volume.^1,60,111 Stroke volume increases progressively during the first and second trimesters, to a peak value of approximately 25% to 30% above nonpregnant values, peaking at 16 to 24 weeks.^27,110 Stroke volume declines during the latter stages of pregnancy, and returns to values that are within the prepregnant range by term.^{22,27,111,158,162} The changes in stroke volume are likely due to increased ventricular muscle mass and end-diastolic volume changes.¹¹¹ As pregnancy advances, the heart rate (see section on Heart Rate), which increases more slowly, becomes a more dominant factor in determining cardiac output.¹¹¹ Figure 9-1 compares the changes in heart rate and stroke volume over gestation.

During pregnancy (especially the third trimester), the resting cardiac output fluctuates markedly with changes in body position.^110,111,160 For example, a change from the left lateral recumbent position to supine can lead to a 25% to 30% decrease in cardiac output.^160,162 Compression of the inferior vena cava by the uterus in the third trimester results in decreased venous return, stroke volume, and cardiac output.¹¹¹ Heart rate changes do not necessarily occur with positional changes; therefore these changes in cardiac output are more likely due to a decrease in stroke volume.^111,160

Twin, triplet, and other multiple pregnancies have a greater increase in cardiac output than do singleton pregnancies, possibly due to an increase in inotropy.⁷⁸ The peak is greater, and the decline in cardiac output seen in late pregnancy is smaller. The cardiac output in multiple pregnancies is higher than that encountered in a singleton pregnancy by 20 weeks’ gestation and remains higher for the remainder of gestation.^78,122

The increase in cardiac output during pregnancy is not related to the metabolic requirements of the mother or the fetus, or to the increase in maternal body mass. At the time the increase in cardiac output occurs, the fetus is relatively small. When fetal growth is accelerated (late in gestation), there is an actual decline in maternal cardiac output. There is, however, a progressive increase in maternal oxygen consumption, which may be due to the rising metabolic needs of the fetus as well as the demands of the maternal heart and respiratory muscles. Pregnancy at high altitudes is associated with less of an increase in cardiac output accompanied by a reduction in the usual expansion of maternal intravascular volume.⁷⁹

The increased oxygen requirements are most likely the result of the contractility-promoting influences of estrogen and progesterone on heart and respiratory muscles and the development of the placental circulation. The placenta functions much like an arteriovenous shunt, with a concomitant decrease in peripheral vascular resistance. Therefore, despite the increase in cardiac output, there is a decrease in mean blood pressure due to a decrease in diastolic pressure. The concomitant increase in blood volume (either in time or magnitude) probably explains the increase in cardiac output. Both begin to rise as early as 6 to 8 weeks’ gestation, peaking toward the end of the second trimester, around 30% to 50% higher than prepregnant levels.^110,111 

Changes in uterine blood flow might also contribute to the increased cardiac output. Progesterone, estrogens, and prolactin may cause changes in hemodynamics by directly affecting the myocardium. For example, estrogens may alter the actomyosin-adenosine triphosphatase (ATP) relationship in the myocardium, thereby increasing the contractility of the heart and altering the stroke volume. Similar effects can be seen with oral contraceptive use.

Heart rate.

Heart rate is the determinant of cardiac output that has the widest range of values. This wide range provides stability to the circulatory system under a variety of circumstances (e.g., from rest to maximal exercise). Heart rate can be altered in order to maintain blood pressure if changes in vascular resistance or stroke volume are encountered. However, an increased heart rate is insufficient to increase cardiac output; it must be accompanied by an increase in venous return. Both heart rate and venous return are increased in pregnancy, contributing to the increase in cardiac output seen throughout gestation.^110,111 The increased heart rate compensates for the decreased SVR and is due to increased myocardial α receptors due to estrogen.^25,68

The maternal heart rate increases progressively during pregnancy, averaging 10 to 20 beats per minute higher (10% to 20% increase) by 32 weeks (see Figure 9-1).^{18,27,65,68,111} At term, the heart rate may return to near baseline levels in some women. Twin pregnancies have an earlier acceleration in heart rate, with a maximum increase 40% above the nonpregnant level near term.³⁴

The increased heart rate results in an elevated myocardial oxygen requirement, which is probably not important in women without cardiac disease, but may become significant in pregnant women with underlying cardiovascular pathology. Beyond this, the increased resting heart rate decreases the maximal work capacity by diminishing the output increment that can be achieved during maximal exercise.¹¹⁰

Blood pressure.

Although there are substantial increases in both blood volume and cardiac output during pregnancy, these changes are not associated with increases in either venous or arterial pressure since the increase in intravenous volume is balanced by the decreased SVR.^18,111 In fact, blood pressure, especially diastolic pressure, is generally reported to decrease, reaching a nadir by midpregnancy.^18,111 The initial decrease is thought to be due to a lag in compensation for changes in peripheral vascular resistance.¹¹¹ The diastolic blood pressure decrease reaches a nadir at 24 to 32 weeks and then gradually returns to nonpregnant baseline values by term (Figure 9-2).^23,27,111 The magnitude of blood pressure changes vary with the position of the woman during measurement. For example, arterial blood pressures are about 10 mmHg higher in sitting or standing than in a left lateral recumbent or supine position.¹¹¹ Serial observations in a sitting or standing position show that as women advance through their pregnancies, systolic blood pressure remains either stable or decreases slightly, whereas diastolic pressure decreases an average of 10 to 15 mmHg (1.33 to 1.99 kPa).^27,111 Mean arterial pressure decreases until midpregnancy, then increases to term.²³ The reduction in blood pressure may be secondary to the vasodilatory effects of nitric oxide, which increases in pregnancy, as well as hormonal and other factors such as prostacyclin and relaxin that mediate a decrease in peripheral vascular resistance.¹²³ Some investigators, have not found this midtrimester fall in blood pressure, but instead reported either no change or a slight rise from the first trimester until late pregnancy.^116,151,165

Techniques and differences in the diastolic measurement point also influence blood pressure measurement. Therefore it is important to use a consistent method and maternal position to evaluate blood pressure.^111,166 Conventional blood pressure techniques often lack standardization in terms of use of appropriate cuff size, equipment calibration, rounding off (to nearest 5 to 10 mmHg [0.66 to 1.33 kPa] versus the recommended 2 mmHg [0.26 kPa]), and method.^57,66

Venous pressures during pregnancy also do not change significantly. Given the large increase in blood volume during pregnancy, an increase in venous pressure would be expected. The increased vascular capacitance and compliance seen during pregnancy explain this lack of change. These alterations are thought to be due to the effects of progesterone and endothelial-derived relaxant factors such as nitric oxide on blood vessel smooth muscle and collagen.^4,111 Venous pressure below the uterus is increased, which may be caused by the increased capacitance encountered in the large pelvic veins and the veins distal to the uterus. The latter may affect venous return to the heart—especially in the upright position—due to regional pooling. The ability to sustain venous return is crucial in determining maternal exercise capacity (see “Exercise during Pregnancy”).¹¹⁰

Systemic vascular resistance.

Changes in cardiac output during pregnancy are accomplished without an increase in arterial pressures because of the marked decrease in SVR, especially in peripheral vessels (reduction in peripheral vascular resistance).^24,158 SVR (mean arterial pressure divided by cardiac output) is decreased 20% to 30% during pregnancy and parallels the decrease in blood pressure.⁶⁵ SVR decreases by 5 weeks and usually reaches its lowest level by 16 to 34 weeks, then progressively increases to term (Figure 9-3).^22,111

The decreased vascular resistance is due to softening of collagen fibers and hypertrophy of smooth muscle, systemic vasodilation due to the vasodilatory effects of progesterone and prostaglandins, remodeling of the maternal spiral arteries (see Chapter 3), fluid retention (leading to blood volume expansion), and the addition of the low-resistance uteroplacental circulation, which receives a large proportion of cardiac output.^26,48,111 The decline in resistance is not limited to the uteroplacental circulation; rather, it is seen throughout the body.⁹⁰ The decreased SVR is also mediated by endothelial prostacyclin, and endothelial-derived relaxant factors (e.g., nitric oxide) that enhance vasodilation.^{24,48,65,111,144} Decreased systemic and renal vascular tone occur very early in pregnancy and precede changes in blood volume.²⁴ Thus the decrease in SVR may be the stimulus for changes in heart rate and stroke volume, and thus cardiac output, in early pregnancy, as well as sodium and water retention (see Chapter 11), and alterations in blood pressure.^24,25,48,111 The hormonal activity of pregnancy also has a role in the reduction of SVR and contributes to changes in regional blood flow. Along with this, the increased heat production (from maternal, fetal, and placental metabolism) stimulates vasodilation of vessels (especially in heat-losing areas such as the hands) and further reductions in resistance.

Regional blood flow.

Much of the increased maternal cardiac output is distributed to the uteroplacental circuit. The increase in cardiac output above the needs of the uteroplacental circulation leads to increased flow to other organ systems, particularly the mammary glands, skin, and kidneys. This creates a reservoir that can be tapped as pregnancy progresses. Blood flow to the splanchnic bed and skeletal muscle perfusion may decrease.⁶⁸

Mammary blood flow is increased. Clinically increased flow is evident by the engorgement that occurs early in pregnancy and the dilation of veins on the surface of the breasts. This dilation is usually accompanied by a sensation of heat and tingling. The effect of pregnancy on coronary artery blood flow is unknown. With the increased workload of the left ventricle (LV) (because of the increased cardiac output, blood volume, fetal growth, uterus enlargement, and body weight gain), it can be assumed that the coronary blood flow is increased to meet the cardiac myometrial demands. Cerebral blood flow is not significantly altered during pregnancy.^111,123 Although absolute blood flow to the liver does not change significantly, the percentage of the cardiac output perfusing the liver decreases.¹¹¹