Medical Physiology, 3rd Edition

Physiology of the Placenta

Eventually, almost all the materials that are necessary for fetal growth and development move from the maternal circulation to the fetal circulation across the placenta, either by passive diffusion or by active transport. Except for CO2, waste products are largely excreted via the amniotic fluid.

At the placenta, the space between the fetus's chorionic villi and the mother's endometrial wall contains a continuously renewed pool of extravasated maternal blood

Within the syncytium of the invading syncytiotrophoblast, fluid-filled holes called lacunae develop 8 to 9 days after fertilization (Fig. 56-5A). Twelve to 15 days after fertilization, the finger-like projections of the syncytiotrophoblast finally penetrate the endothelial layer of small veins of the endometrium. Later, these projections also penetrate the small spiral arteries. The result is a free communication between the lacunae of the syncytiotrophoblast and the lumina of maternal blood vessels (see Fig. 56-5B). Within 12 to 15 days after fertilization, some cytotrophoblasts proliferate and invade the syncytiotrophoblast to form finger-like projections that are the primary chorionic villi.

image

FIGURE 56-5 Development of the placenta. A, Shortly after the blastocyst has implanted (6 to 7 days after fertilization), the syncytiotrophoblast invades the stroma of the uterus (i.e., the decidua). Within the syncytiotrophoblast are lacunae. B, The invading syncytiotrophoblast breaks through into endometrial veins first, and then later into the arteries, creating direct communication between lacunae and maternal vessels. In addition, the proliferation of cytotrophoblasts creates small mounds known as primary chorionic villi. C, The primary chorionic villus continues to grow with the proliferation of cytotrophoblastic cells. In addition, mesenchyme from the extraembryonic coelom invades the villus, forming the secondary chorionic villus. Eventually, these mesenchymal cells form fetal capillaries; at this time, the villus is known as a tertiary chorionic villus. The lacunae also enlarge by merging with one another.

With further development, mesenchymal cells from the extraembryonic mesoderm invade the primary chorionic villi, which now are known as secondary chorionic villi. Eventually, these mesenchymal cells form fetal blood vessels de novo, at which point the villi are known as tertiary chorionic villi (see Fig. 56-5C). Continued differentiation and amplification of the surface area of the fetal tissue that is protruding into the maternal blood creates mature chorionic villi. The outer surface of each villus is lined with a very thin layer of syncytiotrophoblast, which has prominent microvilli (brush border) that face the maternal blood. Beneath the syncytiotrophoblast lie cytotrophoblasts, mesenchyme, and fetal blood vessels. The lacunae, filled with maternal blood, eventually merge with one another to create one massive, intercommunicating intervillous space (Fig. 56-6). The fetal villi protruding into this space resemble a thick forest of trees arising from the chorionic plate, which is the analog of the soil from which the trees sprout. Thus, in the mature placenta, fetal blood is separated from maternal blood only by the fetal capillary endothelium, some mesenchyme and cytotrophoblasts, and syncytiotrophoblast.

image

FIGURE 56-6 Mature placenta. With further development beyond that shown in Figure 56-5C, the outer surface of the mature chorionic villus is covered with a thin layer of syncytiotrophoblast. Under this are cytotrophoblasts, mesenchyme, and fetal blood vessels. The lacunae into which the villi project gradually merge into one massive intervillous space. Maternal blood is trapped in this intervillous space, between the endometrium on the maternal side and the villi on the fetal side. In the mature placenta (shown here), spiral arteries from the mother empty directly into the intervillous space, which is drained by maternal veins. The villi look like a thick forest of trees arising from the chorionic plate, which is the analog of the soil from which the trees sprout.

Maternal Blood Flow

The maternal arterial blood is discharged from ~120 spiral arteries; these arteries may have multiple openings, not all of which need be open at the same time. Blood enters in pulsatile spurts through the wall of the uterus and moves in discrete streams into the intervillous space toward the chorionic plate (see Fig. 56-6). Small lakes of blood near the chorionic plate dissipate the force of the arterial spurts and reduce blood velocity. The maternal blood spreads laterally and then reverses direction and cascades over the closely packed villi. Blood flow slows even more, which allows adequate time for exchange. After bathing the chorionic villi, the maternal blood drains through venous orifices in the basal plate, enters the larger maternal placental veins, and ultimately flows into the uterine and other pelvic veins. No capillaries are present between the maternal arterioles and venules; the intervillous space is the functional capillary. Because the intervillous spaces are very narrow, and the arterial and venous orifices are randomly scattered over the entire base of the placenta, the maternal blood moves efficiently among the chorionic villi and avoids arteriovenous shunts.

The spiral arteries are generally perpendicular, and the veins are generally parallel to the uterine wall. Thus, because of both the geometry of the maternal blood vessels and the difference between maternal arterial and venous pressure, the uterine contractions that occur periodically during pregnancy, as well as during delivery, attenuate arterial inflow and completely interrupt venous drainage. Therefore, the volume of blood in the intervillous space actually increases, providing continual, albeit reduced, exchange. The principal factors that regulate the flow of maternal blood in the intervillous space are maternal arterial blood pressure, intrauterine pressure, and the pattern of uterine contraction.

Fetal Blood Flow

The fetal blood originates from two umbilical arteries. Unlike systemic arteries after birth, umbilical arteries carry deoxygenated blood. As these umbilical arteries approach the placenta, they branch repeatedly beneath the amnion, penetrate the chorionic plate, and then branch again within the chorionic villi, forming a capillary network. Blood that has obtained a significantly higher O2 and nutrient content returns to the fetus from the placenta through the single umbilical vein.

The amniotic fluid that fills the amniotic cavity serves two important functions. First, it serves as a mechanical buffer and thus protects the fetus from external physical insults. Second, it serves as a mechanism by which the fetus excretes many waste products. The water in the amniotic fluid turns over at least once a day. After the fetal kidneys mature (10 to 12 weeks), the fetus's renal excretions provide ~75% of amniotic-fluid production, with pulmonary secretions providing the rest. Fluid removal occurs through the actions of the fetal gastrointestinal tract (~55%), amnion (~30%), and lungs (~15%).

Gases and other solutes move across the placenta

The placenta is the major lifeline between the mother and the fetus. It provides nutrients and O2 to the fetus, and it removes CO2 and certain waste products from the fetus.

O2 and CO2 Transport

The maternal blood coming into the intervillous space has a gas composition similar to that of systemic arterial blood: a partial pressure of oxygen (image) of ~100 mm Hg (Table 56-3), a image of ~40 mm Hg, and a pH of 7.40. However, the diffusion of O2 from the maternal blood into the chorionic villi of the fetus causes the image of blood in the intervillous space to fall, so the average image is 30 to 35 mm Hg. Given the O2dissociation curve of maternal (i.e., adult) hemoglobin (Hb), this image translates to an O2 saturation of ~65% (see Fig. 29-3). The image of blood in the umbilical vein is even lower. Despite the relatively low image of the maternal blood in the intervillous space, the fetus does not suffer from a lack of O2. Because fetal Hb has a much higher affinity for O2 than does maternal Hb (see Box 29-1), the fetal Hb can extract O2 from the maternal Hb. Thus, a image of 30 to 35 mm Hg, which yields an Hb saturation of ~65% in the intervillous space in the mother's blood, produces an Hb saturation of ~85% in the umbilical vein of the fetus (see Table 56-3), assuming that the O2 fully equilibrates between intervillous and fetal blood. Other mechanisms of ensuring adequate fetal oxygenation include the relatively high cardiac output per unit body weight of the fetus and the increasing O2-carrying capacity of fetal blood late in pregnancy as the Hb concentration rises to a level 50% higher than that of the adult.

TABLE 56-3

Maternal and Fetal Oxygen Levels

SITE

image

Hb SATURATION (%)

Maternal Values

Uterine artery

100

97.5

Intervillous space

30–35

57–67

Uterine vein

30

57

Fetal Values

Umbilical arteries

23

60.5

Umbilical vein

30

85.5

The transfer of CO2 from the fetus to the mother is driven by a concentration gradient between the blood in the umbilical arteries and that in the intervillous space. Near the end of pregnancy, the image in the umbilical arteries is ~48 mm Hg, and the image in the intervillous space is ~43 mm Hg, a gradient of ~5 mm Hg. The fetal blood also has a somewhat lower affinity for CO2 than does maternal blood, which favors the transfer of CO2 from the fetus to mother.

Other Solutes

Solutes besides O2 and CO2 move across the placenta between the mother and the fetus, availing themselves of numerous transport mechanisms. Some of these solutes, such as the waste products urea and creatinine, probably move passively from fetus to mother. The lipid-soluble steroid hormones shuttle among the mother, the placenta, and the fetus, perhaps by simple diffusion. Glucose moves from the mother to the fetus by facilitated diffusion (see p. 114), and amino acids move by secondary active transport (see p. 115). The placenta also transports several other essential substances, such as vitamins and minerals, that are needed for fetal growth and development. Many substances are present in the fetal circulation at concentrations higher than in the maternal blood, and they must be actively transported against concentration or electrochemical gradients. The necessary energy (i.e., ATP) is derived from glycolysis and the citric acid cycle, for which the enzymes are present in the human placenta at term. Also present are the enzymes for the pentose phosphate pathway, an alternative pathway for the oxidation of glucose, which provides the reduced nicotinamide adenine dinucleotide phosphate (NADPH) necessary for several synthetic pathways that require reducing equivalents in the human placenta at term. imageN58-5

The placenta takes up large molecules from the mother through receptor-mediated endocytosis (see p. 42). The uptake of substances such as low-density lipoproteins (LDLs), transferrin, hormones (e.g., insulin), and antibodies (e.g., immunoglobulin G) increases throughout gestation until just before birth.

The placenta makes a variety of peptide hormones, including hCG and human chorionic somatomammotropin

The placenta plays a key role in steroid synthesis, as discussed in the next subchapter. In addition, the placenta manufactures numerous amines, polypeptides (including peptide hormones and neuropeptides), proteins, glycoproteins, and steroids (Table 56-4). Among these peptides are the placental variants of all known hypothalamic releasing hormones (see Table 47-2). These placental releasing hormones may act in a paracrine fashion, controlling the release of local placental hormones, or they may enter the maternal or fetal circulations. In addition, several proteases are also present in the placenta. Although the placenta synthesizes a wide variety of substances, the significance of many of these substances is not clear.

TABLE 56-4

Hormones Made by the Placenta

Peptide Hormones and Neuropeptides

Human chorionic gonadotropin (hCG)

Thyrotropin (thyroid-stimulating hormone [TSH])

Placental-variant growth hormone (pvGH)

Human chorionic somatomammotropins 1 and 2 (hCS1 and hCS2), also known as human placental lactogens 1 and 2 (hPL1 and hPL2)

Placental proteins PP12 and PP14

Thyrotropin-releasing hormone (TRH)

Corticotropin-releasing hormone (CRH)

Growth hormone–releasing hormone (GHRH)

Gonadotropin-releasing hormone (GnRH)

Substance P

Neurotensin

Somatostatin

Neuropeptide Y

Adrenocorticotropic hormone (ACTH)–related peptide

Inhibins

Steroid Hormones

Progesterone

Estrone

Estradiol

Estriol

The most important placental peptide hormone is hCG. In the developing blastocyst, and later in the mature placenta, the syncytiotrophoblast cells synthesize hCG, perhaps under the direction of progesterone and estrogens. The placenta also produces two human chorionic somatomammotropins, hCS1 and hCS2, also called human placental lactogens (hPL1, hPL2). hCS1 and hCS2 are polypeptide hormones structurally related to growth hormone (GH) and placental-variant growth hormone (pvGH), as well as to prolactin (PRL; see Table 48-1). They play a role in the conversion of glucose to fatty acids and ketones, and thus coordinate the fuel economy of the fetoplacental unit. The fetus and placenta use fatty acids and ketones as energy sources and store them as fuels in preparation for the early neonatal period, when a considerable reservoir of energy is necessary for the transition from intrauterine life to life outside the uterus. hCS1 and hCS2 also promote the development of maternal mammary glands during pregnancy.

In addition to secreting various substances, the placenta also stores vast amounts of proteins, polypeptides, glycogen, and iron. Many of these stored substances can be used at times of poor maternal nutrition and also during the transition from intrauterine to extrauterine life.

LESION

REFLEXOGENIC ERECTION

PSYCHOGENIC ERECTION

EFFECT ON EJACULATION

Upper motor neuron

Present

Absent

Significantly impaired

Lower motor neuron

Absent

Present

Less impaired