58 Maternal Anatomy and Physiology
SECTION 2
2007). Moreover, in a study of 77 recently delivered gravidas, Gayer and coworkers (2012) found that splenic size was 68-percent larger compared with that of nonpregnant controls.
The cause of this splenomegaly is unknown, but it might follow the increased blood volume and/or the hemodynamic changes of pregnancy, which are subsequently discussed. Sonographically, the echogenic appearance of the spleen remains homogeneous throughout gestation.
CHAPTER 4
substantive ventricular remodeling, which is characterized by eccentric left-ventricular mass expansion averaging 30 to 35 percent near term. In the nonpregnant state, the heart is capa- ble of remodeling in response to stimuli such as hypertension and exercise. Such cardiacplasticityylikely is a continuum that encompasses physiological growth, such as that in exercise, as well as pathological hypertrophy—such as with hypertension (Hill, 2008).
And although it is widely held that there is physiological hypertrophy of cardiac myocytes as a result of pregnancy, this has never been absolutely proven. Hibbard and colleagues (2014) concluded that any increased mass does not meet crite- ria for hypertrophy.
Certainly for clinical purposes, ventricular function dur- ing pregnancy is normal, as estimated by theBraunwald ven- tricular function graph depicted in Figure 4-9. For the given filling pressures, there is appropriate cardiac output so that cardiac function during pregnancy is eudynamic. Despite these findings, it remains controversial whether myocardial function per se is normal, enhanced, or depressed. In non- pregnant subjects with a normal heart who sustain a high-out- put state, the left ventricle undergoeslongitudinal remodeling, and echocardiographic functional indices of its deformation provide normal values. In pregnancy, there instead appears to be spherical remodeling, and these calculated indices that meagg - sure longitudinal deformation are depressed (Savu, 2012).
Thus, these normal indices are likely inaccurate when used to assess function in pregnant women because they do not account for the spherical eccentric hypertrophy characteristic of normal pregnancy.
■ Cardiac Output
During normal pregnancy, mean arterial pressure and vascular resistance decrease, while blood vol- ume and basal metabolic rate increase. As a result, cardiac output at rest, when measured in the lateral recumbent position, increases significantly beginning in early pregnancy (Duvekot, 1993; Mabie, 1994).
It continues to increase and remains elevated during the remainder of pregnancy (Fig. 4-10).
During late pregnancy in a supine woman, the large uterus rather consistently compresses venous return from the lower body. It also may compress the aorta (Bieniarz, 1968). In response, cardiac fill- ing may be reduced and cardiac output diminished.
Specifically, Bamber and Dresner (2003) found car- diac output at term to increase 1.2 L/min—almost 20 percent—when a woman was moved from her back onto her left side. Moreover, in the supine pregnant woman, uterine blood flow estimated by Doppler velocimetry decreases by a third (Jeffreys, 2006). Of note, Simpson and James (2005) found that fetal oxygen saturation is approximately 10 percent higher if a laboring woman is in a lateral recumbent position compared with supine. Upon standing, cardiac output falls to the same degree as in the nonpregnant woman (Easterling, 1988).
In multifetal pregnancies, compared with singletons, mater- nal cardiac output is augmented further by almost another 20 percent because of a greater stroke volume (15 percent) and heart rate (3.5 percent). Left atrial diameter and left ventricular end-diastolic diameter are also increased due to augmented pre- load (Kametas, 2003b). The increased heart rate and inotropic
LVSWI (g·m·m–2)
0
Hyperdynamic
Normal
Depressed
PCWP (mm Hg) 0
30 40 50 60 70 80 90 100 110 120
5 10 15 20 25 30
FIGURE 4-9 Relationship between left ventricular stroke work index (LVSWI), cardiac output, and pulmonary capillary wedge pressure (PCWP) in 10 normal pregnant women in the third trimester. (Data from Clark, 1989.)
0
Weeks’ gestation 1
2 3 4
5 5
Nonpregnant
7.2
8.9 9.3
6.8 7.1
5.8 6.2
6 7
Cardiac output (liters per minute) 8
9 10
20–24 28–32 38–40 Late 2nd-
stage
Immediately postpartum
Labor
Early
FIGURE 4-10 Cardiac output during three stages of gestation, labor, and immediately postpartum compared with values of nonpregnant women.
All values were determined with women in the lateral recumbent position.
(Adapted from Ueland, 1975.)
60 Maternal Anatomy and Physiology
SECTION 2
TABLE 4-4. Central Hemodynamic Changes in 10 Normal Nulliparous Women Near Term and Postpartum
Pregnanta (35–38 wk)
Postpartum
(11–13 wk) Changeb
Mean arterial pressure (mm Hg) 90 ± 6 86 ±8 NSC
Pulmonary capillary wedge pressure (mm Hg) 8 ±2 6 ±2 NSC
Central venous pressure (mm Hg) 4± 3 4±3 NSC
Heart rate (beats/min) 83 ± 10 71 ±10 +17%
Cardiac output (L/min) 6.2 ± 1.0 4.3 ±0.9 +43%
Systemic vascular resistance (dyn/sec/cm−5) 1210± 266 1530 ± 520 −21%
Pulmonary vascular resistance (dyn/sec/cm−5) 78±22 119 ±47 −34%
Serum colloid osmotic pressure (mm Hg) 18.0± 1.5 20.8 ± 1.0 −14%
g ( g)
COP-PCWP gradient (mm Hg) 10.5± 2.7 14.5 ± 2.5 −28%
Left ventricular stroke work index (g/m/m2) 48 ±6 41 ±8 NSC
aMeasured in lateral recumbent position.
bChanges significant unless NSC=no significant change.
COP=colloid osmotic pressure; PCWP =pulmonary capillary wedge pressure.
Adapted from Clark, 1989.
contractility imply that cardiovascular reserve is reduced in multifetal gestations.
During the first stage of labor, cardiac output increases moderately. During the second stage, with vigorous expulsive efforts, it is appreciably greater (see Fig. 4-10). The pregnancy- induced increase is lost after delivery, at times dependent on blood loss.
■ Hemodynamic Function in Late Pregnancy
To further elucidate the net changes of normal pregnancy- induced cardiovascular changes, Clark and associates (1989) conducted invasive studies to measure hemodynamic func- tion late in pregnancy (Table 4-4). Right heart catheter- ization was performed in 10 healthy nulliparous women at 35 to 38 weeks, and again at 11 to 13 weeks postpartum.
Late pregnancy was associated with the expected increases in heart rate, stroke volume, and cardiac output. Systemic vascular and pulmonary vascular resistance both decreased significantly, as did colloid osmotic pressure. Pulmonary capillary wedge pressure and central venous pressure did not change appreciably between late pregnancy and the puerpe- rium. Thus, as shown earlier in Figure 4-9, although cardiac output is increased, left ventricular function as measured by stroke work index remains similar to the nonpregnant nor- mal range. Put another way, normal pregnancy is not a con- tinuous “high-output” state.
■ Circulation and Blood Pressure
Changes in posture affect arterial blood pressure. Brachial artery pressure when sitting is lower than that when in the lateral recumbent supine position (Bamber, 2003). Arterial pressure usually decreases to a nadir at 24 to 26 weeks and rises thereafter. Diastolic pressure decreases more than systolic (Fig. 4-11).
Antecubital venous pressure remains unchanged during preg- nancy. In the supine position, however, femoral venous pressure rises steadily, from approximately 8 mm Hg early in pregnancy to 24 mm Hg at term. Wright and coworkers (1950) demon- strated that venous blood flow in the legs is retarded during preg- nancy except when the lateral recumbent position is assumed.
This tendency toward blood stagnation in the lower extremities during latter pregnancy is attributable to occlusion of the pelvic veins and inferior vena cava by the enlarged uterus. The elevated venous pressure returns to normal when the pregnant woman lies on her side and immediately after delivery (McLennan, 1943). These alterations contribute to the dependent edema
120 Supine
Gestation (weeks) SYSTOLIC
Blood pressure (mm Hg)
Left lateral recumbent
DIASTOLIC 110
100 90 80 70 60 50 40 0
0 4 8 12 16 20 24 28 32 36 40 PP FIGURE 4-11 Sequential changes (±SEM) in blood pressure throughout pregnancy in 69 women in supine (blue lines) and left lateral recumbent positions (red lines). PP =postpartum.
(Adapted from Wilson, 1980.)
CHAPTER 4
frequently experienced and to the development of varicose veins in the legs and vulva, as well as hemorrhoids. These changes also predispose to deep-vein thrombosis (Chap. 52, p. 1035).
Supine Hypotension
In approximately 10 percent of women, supine compression of the great vessels by the uterus causes significant arterial hypotension, sometimes referred to as the supine hypotensive syndromee (Kinsella, 1994). Also when supine, uterine arterial pressure—and thus blood flow—is significantly lower than that in the brachial artery. As discussed in Chapter 24 (p. 494), this may directly affect fetal heart rate patterns (Tamás, 2007).
These changes are also seen with hemorrhage or with spinal analgesia (Chap. 25, p. 511).
■ Renin, Angiotensin II, and Plasma Volume
The renin-angiotensin-aldosterone axis is intimately involved in blood pressure control via sodium and water balance. All components of this system are increased in normal pregnancy (Bentley-Lewis, 2005). Renin is produced by both the maternal kidney and the placenta, and increased renin substrate (angioten- sinogen) is produced by both maternal and fetal liver. Elevated angiotensinogen levels result, in part, from increased estrogen production during normal pregnancy and are important in first- trimester blood pressure maintenance (August, 1995).
Gant and associates (1973) studied vascular reactivity to angiotensin II throughout pregnancy. Nulliparas who remained normotensive became and stayed refractory to the pressor effects of infused angiotensin II. Conversely, those who ultimately became hypertensive developed, but then lost, this refractori- ness. Follow-up studies by Gant (1974) and Cunningham (1975) and their colleagues indicated that increased refractori- ness to angiotensin II stemmed from individual vessel refractori- ness. Said another way, the abnormally increased sensitivity was an alteration in vessel wall refractoriness rather than the conse- quence of altered blood volume or renin-angiotensin secretion.
The vascular responsiveness to angiotensin II may be progesterone related. Normally, pregnant women lose their acquired vascular refractoriness to angiotensin II within 15 to 30 minutes after the placenta is delivered. Moreover, large amounts of intramuscular progesterone given dur- ing late labor delay this diminishing refractoriness. And although exogenous progesterone does not restore angio- tensin II refractoriness to women with gestational hyperten- sion, this can be done with infusion of its major metabolite, 5α-dihydroprogesterone.
■ Cardiac Natriuretic Peptides
At least two species of these—atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)—are secreted by cardio- myocytes in response to chamber-wall stretching. These pep- tides regulate blood volume by provoking natriuresis, diuresis, and vascular smooth-muscle relaxation (Clerico, 2004). In nonpregnant and pregnant patients, levels of BNP and of amino-terminal pro-brain natriuretic peptide (Nt pro-BNP) may be useful in screening for depressed left ventricular systolic
function and determining chronic heart failure prognosis (Jarolim, 2006; Tanous, 2010).
During normal pregnancy, plasma ANP and BNP levels are maintained in the nonpregnant range despite increased plasma volume (Lowe, 1992; Yurteri-Kaplan, 2012). In one study, Resnik and coworkers (2005) found median BNP levels to be stable across pregnancy with values< 20 pg/mL. BNP levels are increased in severe preeclampsia, and Tihtonen and colleagues (2007) concluded that this was caused by cardiac strain from increased afterload. It would appear that ANP- induced physiological adaptations participate in extracellular fluid volume expansion and in the increased plasma aldoste- rone concentrations characteristic of normal pregnancy.
A third species,C-type natriuretic peptide (CNP),is predomi- nantly secreted by noncardiac tissues. Among its diverse bio- logical functions, this peptide appears to be a major regulator of fetal bone growth. Walther and Stepan (2004) have provided a detailed review of its function during pregnancy.
■ Prostaglandins
Increased prostaglandin production during pregnancy is thought to have a central role in control of vascular tone, blood pressure, and sodium balance. Renal medullary prostaglandin E2 synthesis is increased markedly during late pregnancy and is presumed to be natriuretic. Prostacyclin (PGI2), the princi- pal prostaglandin of endothelium, also is increased during late pregnancy and regulates blood pressure and platelet function.
It also has been implicated in the angiotensin resistance char- acteristic of normal pregnancy (Friedman, 1988). The ratio of PGI2 to thromboxane in maternal urine and blood has been considered important in preeclampsia pathogenesis (Chap. 40, p. 735). The molecular mechanisms regulating prostacyclin pathways during pregnancy have recently been reviewed by Majed and Khalil (2012).
■ Endothelin
There are several endothelins generated in pregnancy.
Endothelin-1 is a potent vasoconstrictor produced in endo- thelial and vascular smooth muscle cells and regulates local vasomotor tone (Feletou, 2006; George, 2011). Its produc- tion is stimulated by angiotensin II, arginine vasopressin, and thrombin. Endothelins, in turn, stimulate secretion of ANP, aldosterone, and catecholamines. As discussed in Chapter 21 (p. 427), there are endothelin receptors in pregnant and non- pregnant myometrium. Endothelins also have been identified in the amnion, amnionic fluid, decidua, and placenta (Kubota, 1992; Margarit, 2005). Vascular sensitivity to endothelin-1 is not altered during normal pregnancy. Ajne and associates (2005) postulated that vasodilating factors counterbalance the endothelin-1 vasoconstrictor effects and reduce peripheral vascular resistance.
■ Nitric Oxide
This potent vasodilator is released by endothelial cells and may have important implications for modifying vascular resistance during pregnancy. Moreover, nitric oxide is one of the most
62 Maternal Anatomy and Physiology
SECTION 2
important mediators of placental vascular tone and develop- ment (Krause, 2011; Kulandavelu, 2013). As discussed in Chapter 40 (p. 735), abnormal nitric oxide synthesis has been linked to preeclampsia development (Baksu, 2005; Teran, 2006).