Which physiological change causes a postpartum increase in circulating blood volume?

Intervillous Space PaO2

Oxygenated maternal blood leaves the maternal heart with a partial pressure of oxygen dissolved in arterial blood (PaO2) of approximately 95 to 100 mm Hg. Exiting the spiral arteries to perfuse the intervillous space of the placenta, oxygenated maternal blood has a PaO2 of approximately 95 to 100 mm Hg. Oxygen is released from maternal hemoglobin and diffuses across the placental blood-blood barrier into fetal blood, where it combines with fetal hemoglobin. As a result, maternal blood in the intervillous space becomes relatively oxygen depleted and exits the intervillous space via uterine veins with a PaO2 of approximately 40 mm Hg (Fig. 15-6).

The average PaO2 of maternal blood in the intervillous space is between the PaO2 of blood entering the intervillous space (95 to 100 mm Hg) and the PaO2 of blood exiting the intervillous space (40 mm Hg). The average intervillous space PaO2 is in the range of 45 mm Hg. Interruption of fetal oxygenation can result from conditions that reduce the PaO2 of maternal blood entering the intervillous space. These conditions have been discussed previously.

Placenta

Maternal blood bathes the chorionic villi, which consist of a layer of trophoblastic cells that enclose fetal capillaries. Their large surface area and the high placental blood flow (500 mL/min) are essential for gas exchange, uptake of nutrients and elimination of waste products. Thus a lipid barrier separates the fetal and maternal bloodstreams, allowing the passage of lipid-soluble substances but excluding water-soluble compounds, especially those with a molecular weight exceeding 600.4

This exclusion is of particular importance with short-term use, e.g. tubocurarine (mol. wt. 772) (lipid insoluble) or gallamine (mol. wt. 891) used as a muscle relaxant during caesarean section do not affect the infant; with prolonged use, however, all compounds will eventually enter the fetus to some extent (see Index).

Maternal Phenylketonuria Syndrome

Elevated maternal blood phenylalanine levels can cross the placenta and cause fetal birth defects including microcephaly, dysmorphic features, and congenital heart defects. More than 90% of children born to women with untreated classic PKU have mental retardation. The risk to the fetus is greatest with increasing maternal blood phenylalanine levels. For optimal physical and cognitive fetal outcomes, it is strongly recommended that dietary control be achieved before conception and that mothers with PKU be monitored carefully by an experienced center throughout pregnancy. Even at maternal phenylalanine levels of <360 μM, 6% of infants are born with microcephaly and 4% with postnatal growth retardation.

Cardiovascular Physiology

Maternal blood volume increases progressively throughout pregnancy, peaking at a level 40% above baseline by the third trimester. The increase in blood volume provides some protection against peripartum blood loss. The cardiac output increases from as early as 5 weeks' gestation, reaching 30% to 50% above baseline levels by 25 to 32 weeks (see Fig. 59.2). Heart rate rises to a level 10% to 30% above prepartum values by 32 weeks. Left atrial and left ventricular (LV) end-diastolic dimensions enlarge, and LV wall thickness and LV mass increase. Systemic blood pressure decreases slightly during pregnancy, with diastolic pressure falling 10% to 20% and reaching a nadir at 28 weeks. The decrease in systolic pressure is less marked, resulting in an increased pulse pressure. Blood pressure slowly increases throughout the third trimester but remains below prepregnancy values. Hemodynamic measurements by pulmonary artery catheter in the near-term patient reveal an increased cardiac output, with systemic vascular resistance and pulmonary vascular resistance decreased by 20% to 30%. The central venous pressure and pulmonary capillary wedge pressure are not different from nonpregnant values (Table 59.1).

Near term, the enlarged uterus may compress the vena cava in the supine patient, which can decrease venous return, causing a drop in cardiac output, sometimes associated with reflex vasovagal effects. Further hemodynamic changes occur during labor and in the immediate postpartum period. Cardiac output increases by about 10% to 15% during labor, augmented further during contractions, due to the return of 300 to 500 mL of blood to the central circulation. Similarly, immediately after delivery there is an increase in preload, resulting in an increased cardiac output. Cardiac output remains elevated at the levels seen during pregnancy for about 2 days postdelivery.

Maternal PKU Syndrome

Elevated maternal blood phenylalanine levels can cross the placenta and cause fetal birth defects, including microcephaly, dysmorphic features, and congenital heart defects. More than 90% of children born to women with untreated classic PKU have mental retardation, with microcephaly being present in 70% of cases, intrauterine growth retardation in 40%, and congenital heart disease in 12%. The risk to the fetus is greatest with increasing maternal blood phenylalanine levels. The maternal PKU syndrome is especially tragic given that these children are typically heterozygous for the mutant PAH gene and would not be affected with PKU. For optimal physical and cognitive fetal outcomes, it is strongly recommend that dietary control be achieved before conception and that mothers with PKU be monitored carefully by an experienced center throughout pregnancy. Blood phenylalanine levels should be maintained between 120 and 360 μM.

Plasma Volume and Red Cell Mass

Maternal blood volume begins to increase at about 6 weeks' gestation. Thereafter, it rises progressively until 30 to 34 weeks and then plateaus until delivery. The average expansion of blood volume is 40% to 50% (range 20% to 100%). Women with multiple pregnancies have a larger increase in blood volume than those with singletons. Likewise, volume expansion correlates with infant birthweight, but it is not clear whether this is a cause or an effect. The increase in blood volume results from a combined expansion of both plasma volume and red blood cell (RBC) mass. The plasma volume begins to increase by 6 weeks and expands at a steady pace until it plateaus at 30 weeks' gestation; the overall increase is about 50% (1200 to 1300 mL). The exact etiology of the expansion of the blood volume is unknown, but the hormonal changes of gestation and the increase in nitric oxide (NO) play important roles.

Erythrocyte mass also begins to expand at about 10 weeks' gestation. Although the initial slope of this increase is slower than that of the plasma volume, erythrocyte mass continues to grow progressively until term without plateauing. Without iron supplementation, RBC mass increases about 18% by term, from a mean nonpregnant level of 1400 mL up to 1650 mL. Supplemental iron increases RBC mass accumulation to 400 to 450 mL, or 30%, and a corresponding improvement is seen in hemoglobin levels. Because plasma volume increases more than the RBC mass, maternal hematocrit falls. This so-called physiologic anemia of pregnancy reaches a nadir at 30 to 34 weeks. Because the RBC mass continues to increase after 30 weeks when the plasma volume expansion has plateaued, the hematocrit may rise somewhat after 30 weeks (Fig. 3-6). The mean and fifth-percentile hemoglobin concentrations for normal iron-supplemented pregnant women are outlined in Table 3-3. A hemoglobin level that reaches its nadir at 9 to 11 g/dL has been associated with the lowest rate of perinatal mortality, whereas values below or above this range have been linked to an increased perinatal mortality.23

In pregnancy, erythropoietin levels increase twofold to threefold, starting at 16 weeks, and they may be responsible for the moderate erythroid hyperplasia found in the bone marrow and for the mild elevations in the reticulocyte count. The increased blood volume is protective given the possibility of hemorrhage during pregnancy or at delivery. The larger blood volume also helps fill the expanded vascular system created by vasodilation and by the large, low-resistance vascular pool within the uteroplacental unit, thereby preventing hypotension.18

Vaginal delivery of a singleton infant at term is associated with a mean blood loss of 500 mL; an uncomplicated cesarean delivery, about 1000 mL; and a cesarean hysterectomy, 1500 mL.24 In a normal delivery, almost all of the blood loss occurs in the first hour. Pritchard and colleagues24 found that over the subsequent 72 hours, only 80 mL of blood is lost. Gravid women respond to blood loss in a different fashion than in the nonpregnant state. In pregnancy, the blood volume drops after postpartum bleeding, but no reexpansion to the prelabor level occurs, and less of a change is seen in the hematocrit. Indeed, instead of volume redistribution, an overall diuresis of the expanded water volume occurs postpartum. After delivery with average blood loss, the hematocrit drops moderately for 3 to 4 days, followed by an increase. By days 5 to 7, the postpartum hematocrit is similar to the prelabor hematocrit. If the postpartum hematocrit is lower than the prelabor hematocrit, either the blood loss was greater than appreciated, or the hypervolemia of pregnancy was less than normal, as in preeclampsia.24

Villitis or intervillositis caused by haematogenous infection

Because maternal blood supplies the intervillous space, maternal systemic diseases may involve the placenta, leading to either collections of inflammatory cells or fibrin within the intervillous space (e.g., malaria), or inflammation of the villi (villitis; e.g., cytomegalovirus). When there is villitis from an infective cause, which may be viral, bacterial or protozoal, the placenta usually demonstrates patchy but diffuse involvement, with florid focal villitis, which may even be associated with villous necrosis or granuloma formation. The pattern of tissue involvement may suggest a particular organism as the aetiology, but confirmation should always be based on additional ancillary investigations. In some cases of viral infection, characteristic viral cellular inclusions may be present, making the specific diagnosis more definitive.

3.4 How Maternal Hypertriglyceridemia May Benefit the Fetus and the Newborn

Increased maternal blood TG are a typical finding during pregnancy. Although TG do not directly cross the placenta, they may benefit the fetus in various ways.

Maternal TG represent a “floating energy depot” [1]. Under fasting condition, TG are efficiently used by the maternal liver to synthesize ketone bodies. This mechanism spares glucose for use by the fetus for energy.

Maternal TG should be considered a “reservoir for maternal fatty acids” derived from the diet. Placenta uptake of maternal TG is concentration dependent [1]. Hydrolysis by LPL and other lipases releases FFA for the fetus.

Maternal hypertriglyceridemia may also contribute to newborn development via increased milk synthesis for subsequent lactation (Fig. 2) [1].

At the time of delivery, LPL expression and activity increase in the mammary glands [1]. These changes are caused by increased insulin and prolactin in association with enhanced insulin mammary gland sensitivity and decreased adipose tissue insulin sensitivity. These metabolic changes drive TG to the mammary glands where LPL induction facilitates clearance of circulating TG for milk synthesis. EFA (derived from the maternal diet) thus become available and contribute to newborn development.

Blood volume, blood and plasma changes

These result in the ‘hypervolemia of pregnancy’ – an increase in blood volume and blood plasma.

Circulating maternal blood volume increases by about 30% and sometimes more (up to 40% primipara, 60% multipara). This represents an increase of approximately 1.5 L (Chesley 1972). The increased blood volume is due to an increase in plasma volume, with a lesser increase in total red blood cell (RBC) count. Blood volume changes begin at 6–8 weeks, peak at 30–34 weeks, then reach a plateau towards term.

Plasma volume change begins at 6–8 weeks, increases rapidly in the second trimester, followed by a slower but progressive increase which reaches its maximum around 28–32 weeks. At its peak it is about 50% greater than pre-pregnancy levels. The enlarged plasma volume is accommodated by changes in vascularisation of the uterus, breast, muscles, kidneys and skin. Increased blood flow to the uterus accounts for about 16 of the increase. Uterine blood flow increases by about 150%. Renal blood flow is the next most significant. Plasma proteins (albumin) are also diluted.

Plasma volume, placental mass and birth weight are closely associated and fetal growth correlates more to plasma changes than increases in RBC. The exact aetiology is poorly understood but is influenced by hormonal influences on the vasculature of the circulatory system which lead to decreased venous tone, increased capacity of the veins and muscles and decreased vascular resistance. The vascular system expands as progesterone stimulates the vasodilation of the vascular smooth muscle and oestrogen stimulates angiogenesis (formation of new blood vessels and vascular beds) and increased blood flow.

Both progesterone and oestrogen, along with aldosterone, affect the renin–angiotensin system (RAS; hormone system regulating long-term blood pressure and volume). RAS responds to the under-filled vascular system by increasing sodium and water retention; thus blood volume increases by about 40%.

Blood Volume

Expansion of maternal blood volume is detectable as early as the fourth week of pregnancy. The blood volume continues to expand until approximately 28–34 weeks of gestation, after which it plateaus until delivery. Most of this expansion is the result of changes in plasma volume, which increases to values 30 to 50 percent above the nonpregnant state by the end of pregnancy. In addtion, there is an increase in red blood cell mass beginning at 8–10 weeks of gestation, to approximately 25 pecent over nonpregnant values by delivery, provided that iron intake is adequate. Because plasma volume expansion exceeds the increase in red blood cell mass, “physiologic anemia” with a decreased hematocrit generally develops most prominently during the third trimester, although oxygen carrying capacity is increased over that of the nonpregnant state.1–4