Physiology of Parturition

Question 1

Answer 1

Question 2

Phase 0

Answer 2

•uterine quiescence

Question 3

Answer 3

Question 4

Progesterone

Answer 4

•increases uterine quiescence

Question 5

Relaxin

Answer 5

•Relaxin is a member of the insulin-like growth factor family of proteins. Plasma levels are highest at 8 to 12 weeks of gestation and thereafter decline to low levels, which persist until term. The primary source of relaxin is thought to be the corpus luteum. Relaxin appears to act indirectly to promote myometrial relaxation by stimulating myometrial prostacyclin production.

Question 6

Parathyroid Hormone-related Protein (PTH-rP)

Answer 6

•PTH-rP expression in smooth muscle is increased by muscle stretch which may facilitate uterine tranquility.

Question 7

Corticotropin-releasing Hormone (CRH)

Answer 7

•In humans the timing of birth is associated with the development of the placenta — in particular, with expression of the gene for corticotropin-releasing hormone (CRH) by the placenta.

Question 8

Maternal CRH

Answer 8

•Maternal plasma CRH levels increase exponentially as pregnancy advances, peaking at the time of delivery. In women who deliver preterm, the exponential increase is rapid, whereas in women who deliver after the estimated date of delivery, the rise is slower. These findings suggest that a placental clock determines the timing of delivery.

Question 9

CRH Receptors

Answer 9

•CRH is secreted from the placenta predominantly into the maternal blood, but it also enters the fetal circulation. In the mother, CRH receptors are present in the pituitary, the myometrium, and probably the adrenal glands. In the fetus, there are CRH receptors in the pituitary, the adrenal glands, and perhaps the lungs. Rising levels of CRH can therefore act at multiple sites in mother and fetus to initiate the changes associated with parturition.

Question 10

CRH in the Fetus

Answer 10

•Placental CRH is also released into the fetus, and although the concentrations are lower in the fetal circulation than in the maternal circulation, they still rise with advancing gestation. Stimulation of the fetal pituitary by CRH increases corticotropin production and, consequently, the synthesis of cortisol and DHEA-S by the fetal adrenal gland and maturation of the fetal lungs. In turn, the rising cortisol concentrations in the fetus further stimulate placental CRH production. The maturation of the fetal lungs as a result of increasing cortisol concentrations is associated with increased production of surfactant protein A and phospholipids, both of which have proinflammatory actions and may stimulate myometrial contractility through increased production of prostaglandins by fetal membranes and the myometrium itself.

Question 11

Phase 1

Answer 11

•preparation for labor

Question 12

Phase 1: Uterus

Answer 12

Question 13

Phase 1: Activation of Myometrium at Term

Answer 13

• An important event in labor is the expression of a group of proteins termed “contraction associated proteins.”
• These proteins act within the uterus, which is in a relaxed state for most of pregnancy, to initiate the powerful rhythmic contractions that force the fetus through a softening cervix at term.
• There are three types of contraction-associated proteins: those that enhance the interactions between the actin and myosin proteins that cause muscle contraction, those that increase the excitability of individual myometrial cells, and those that promote the intercellular connectivity that permits the development of synchronous contractions.

Question 14

Phase 1: Proteins That Promote Myocyte Contractility

Answer 14

• Interactions between actin and myosin determine myocyte contractility.
• For these interactions to occur, actin must be converted from a globular to a filamentous form.
• Actin must also attach to the cytoskeleton at focal points in the cell membrane that allow the development of tension; these focal points link the cell to the underlying matrix.
• Actin’s partner, myosin, is activated when it is phosphorylated by myosin light-chain kinase.
• Calmodulin and increased intracellular calcium activate this enzyme.
• During labor, an influx of extracellular calcium through voltage regulated calcium channels and the release of calcium from intracellular stores result in increased intracellular calcium, thereby promoting myosin–actin interactions and, consequently, contraction.

Question 15

Phase 1: Proteins That Increase Myocyte Excitability

Answer 15

• Myocytes maintain an electrochemical potential gradient across the plasma membrane, with the interior negative to the exterior, through the action of the sodium–potassium exchange pump.
• At the time of labor, changes in the distribution and function of these channels lower the intensity of the stimulus required to depolarize myocytes and to produce the associated influx of calcium that generates contraction.

Question 16

Phase 1: Proteins That Promote Intercellular Connectivity

Answer 16

• A critical aspect of myometrial activity at labor is the development of synchrony.
• Synchronous activity of myometrial cells results in the powerful contractions needed to expel the fetus. Equally important are the intervening periods of relaxation, which permit blood flow to the fetus (during contraction, blood flow to the fetus decreases, and during relaxation, it increases).
• The uterus lacks a pacemaker that regulates the contractions. However, as parturition progresses, there is increasing synchronization of the electrical activity of the uterus.
• At the cellular level, this synchrony is achieved by electrical conduction through connecting myofibrils, which transmit the electrical activity to nearby muscle fibers. This process leads to a wave of activity as more and more myocytes are recruited into the contraction. After contraction, the myocytes relax and become refractory to further stimulation.
• The typical uterine contraction consists of a slow rise and fall of tension lasting close to a minute.

Question 17

Phase 1: Fetal Contributions to Parturition

Answer 17

• As term approaches, there are increasing concentrations of placental CRH, a boost in the synthesis of corticotropin by the fetal pituitary, and heightened steroidogenesis in the fetal adrenal glands.
• Rising fetal concentrations of cortisol induce maturation of many fetal tissues, especially the lungs. The maturing fetal lungs increase production of the surfactant proteins and phospholipids that are critical for lung function.
• The amniotic fluid surfactant proteins may well stimulate the inflammation that is observed in the adjacent fetal membranes, cervix, and underlying myometrium at the time of labor.

Question 18

Phase 1: Fetal Membrane Activation

Answer 18

• The amnion lies in direct contact with the amniotic fluid, giving constituents of the amniotic fluid unrestricted access to the amnion.
• The production of surfactant proteins, phospholipids, and inflammatory cytokines in the amniotic fluid increases as cyclooxygenase-2 (COX-2) activity and prostaglandin E2 production increase in the amnion. Concurrently, levels of cortisol and CRH rise in the amniotic fluid.
• Prostaglandins and CRH mediate the release of the metalloproteases that weaken the placental membranes, thereby facilitating membrane rupture.

Question 19

Phase 1: Cervical Softening

Answer 19

•A critical component of normal parturition is the softening of the cervix. Parturition is associated with movement of an inflammatory infiltrate, including prostaglandins, into the cervix and the release of metalloproteases that degrade collagen, thus changing the structure of the cervix. The levels of prostaglandins, particularly PGF2 and PGE2 are increased in amniotic fluid, maternal plasma and maternal urine are increased during labor.

Question 20

Phase 1: The Role of Progesterone Withdrawal

Answer 20

•While progesterone levels due not drop prior to the onset of labor, it is hypothesized that myometrial activation involves an effective or physiologic progesterone withdrawal through blockage of progesterone receptors through a yet unidentified mechanism.

Question 21

Phase 1: The Role of Oxytocin

Answer 21

•Circulating levels of oxytocin do not change significantly during pregnancy or prior to the onset of labor. However, myometrial oxytocin receptor concentrations increase approximately 100 to 200-fold during pregnancy, reaching a maximum during early labor. This rise in receptor concentration accounts for the increased sensitivity of the myometrium to circulating levels of oxytocin later in pregnancy. Oxytocin acts on decidual tissue to promote prostaglandin release.

Question 22

Phase 2

Answer 22

Question 23

Phase 2: The Stages of Labor

Answer 23

1. Cervical Effacement and Dilation
2. Delivery of Infant
3. Delivery of Placenta

Question 24

Phase 2: Stage 1 of Labor

Answer 24

•Widely spaced uterine contractions of sufficient frequency, intensity and duration are attained to bring about effacement of the cervix. This stage of labor ends when the cervix is fully dilated (about 10 cm) to allow passage of the baby’s head.

Question 25

Phase 2: Stage 2 of Labor

Answer 25

•This stage begins when the cervix is fully dilated, and ends when the baby is delivered. At the beginning of the normal second stage, the head is fully engaged in the pelvis; the widest diameter of the head has passed through the pelvic inlet.

Question 26

Cardinal Movement of Stage 2 of Labor

Answer 26

1. Engagement of the fetal head in the transverse position. The baby is looking across the pelvis at one of the mother’s hips.
2. Descent of the fetal head
3. Flexion of the fetal head
4. Internal rotation. The fetal head rotates 90 degrees to the occiput anterior so that the baby’s face is towards the mother’s rectum.
5. Extension. The fetal head reaches the pelvic floor, and is directed to the vulvar opening. With progressive distension of the perineum and vaginal opening, an increasingly larger portion of the fetal head appears.
6. External rotation (restitution). The fetal head turns through 45 degrees to restore its normal relationship with the shoulders, which are still at an angle.
7. Expulsion. The anterior shoulder appears under the symphysis pubis and the perineum becomes distended by the posterior shoulder. The rest of the body follows easily after the shoulders.

Question 27

Phase 2: Stage 3 of Labor

Answer 27

•Begins immediately after delivery of the infant and ends with delivery of the placenta and membranes.

Question 28

Phase 3

Answer 28

Question 29

Phase 3: Stages of Postpartum Period

Answer 29

•The postpartum period has been arbitrarily divided into the immediate puerperium, the first 24 hours after parturition, when acute postanesthetic or postdelivery complications may occur; the early puerperium, which extends until the first week postpartum; and the remote puerperium, which includes the period of time required for involution of the genital organs and return of menses, usually by 6 weeks in nonlactating women, and the return of normal cardiovascular and psychological function, which may require months.

Question 30

Phase 3: Uterine Involution

Answer 30

• Immediately after the delivery of the newborn, the endocrine status of the mother changes dramatically. As hormone levels drop, the vasculature of the uterus regresses and blood flow to the uterus declines. The uterus involutes. Myometrial contractions assist in involution. These contractions occur during the first 2-3 days of the puerperium and produce more discomfort in multiparas than in primiparas. Such pains are accentuated during nursing as a result of oxytocin release from the posterior pituitary. These contractions, as well as arterial smooth muscle contractions, lead to hemostasis. During the first 12 hours postpartum, uterine contractions are regular, strong, and coordinated. The intensity, frequency, and regularity of contractions decrease after the first postpartum day as involutional changes proceed.
• Uterine involution is nearly complete by 6 weeks, at which time the organ weighs less than 100 g. The increase in the amount of connective tissue and elastin in the myometrium and blood vessels and the increase in numbers of cells are permanent to some degree, so the uterus is slightly larger following pregnancy.
• Immediately following delivery, the uterus weighs about 1 kg, and its size approximates that of a 20-week pregnancy (at the level of the umbilicus). At the end of the first postpartum week, it normally will have decreased to the size of a 12-week gestation and is just palpable at the symphysis pubis.

Question 31

Phase 3: Uterine Discharge

Answer 31

• Normal postpartum discharge begins as lochia rubra, containing blood, shreds of tissue, and decidua.
• The amount of discharge rapidly tapers and changes to a reddish-brown color over the next 3-4 days.
• It is termed lochia serosa when it becomes serous to mucopurulent, paler, and often malodorous.
• During the second or third postpartum week, the lochia becomes thicker, mucoid, and yellowish-white (lochia alba), coincident with a predominance of leukocytes and degenerated decidual cells.
• Typically during the fifth or sixth week postpartum, the lochial secretions cease as healing nears completion.

Question 32

Phase 3: Changes in Cervix, Vagina, Muscular Walls of Pelvic Organs

Answer 32

• The cervix gradually closes during the puerperium; at the end of the first week, it is little more than 1 cm dilated. The external os is converted into a transverse slit, thus distinguishing the parous woman who delivered vaginally from the nulliparous woman or from one who delivered by cesarean section.
• After vaginal delivery, the overdistended and smooth-walled vagina gradually returns to its antepartum condition by about the third week.
• Ovulation occurs as early as 27 days after delivery, with a mean time of 70-75 days in nonlactating women and 6 months in lactating women. In lactating women the duration of anovulation ultimately depends on the frequency of breastfeeding, duration of each feed, and proportion of supplementary feeds. Ovulation suppression is due to high prolactin levels, which remain elevated until approximately 3 weeks after delivery in nonlactating women and 6 weeks in lactating women. However, estrogen levels fall immediately after delivery in all mothers and remain suppressed in lactating mothers. Menstruation returns as soon as 7 weeks in 70% and by 12 weeks in all nonlactating mothers, and as late as 36 months in 70% of breastfeeding mothers.

Question 33

Phase 3: Urinary System

Answer 33

•Pregnancy is accompanied by an estimated increase of about 50% in the glomerular filtration rate. These values return to normal or less than normal during the eighth week of the puerperium. Endogenous creatinine clearance similarly returns to normal by 8 weeks.

Question 34

Phase 3: Fluid Balance and Electrolytes

Answer 34

• An average decrease in maternal weight of 10-13 lb occurs intrapartum and immediately postpartum due to the loss of amniotic fluid and blood as well as delivery of the infant and placenta.
• The average patient may lose an additional 4 kg (9 lb) during the puerperium and over the next 6 months as a result of excretion of the fluids and electrolytes accumulated during pregnancy.
• Contrary to widespread belief, breastfeeding has minimal effects on hastening weight loss postpartum.

Question 35

Phase 3: Pituitary-Ovarian Relationships

Answer 35

• The plasma levels of placental hormones decline rapidly following delivery.
• Human placental lactogen has a half-life of 20 minutes and reaches undetectable levels in maternal plasma during the first day after delivery.
• Human chorionic gonadotropin (hCG) has a mean half-life of about 9 hours. The concentration of hCG in maternal plasma falls below 1000 mU/mL within 48- 96 hours postpartum and falls below 100 mU/mL by the seventh day.
• Within 3 hours after removal of the placenta, the plasma concentration of 17-estradiol falls to 10% of the antepartum value.
• By the third day of the puerperium, the plasma progesterone concentrations are below luteal phase levels (1 ng/mL).
• Plasma estrogens do not reach follicular phase levels (50 pg/mL) until 19-21 days postpartum in nonlactating women. The return to normal plasma levels of estrogens is delayed in lactating women. Lactating women who resume spontaneous menses achieve follicular phase estradiol levels (50 pg/mL) during the first 60-80 days postpartum. Lactating amenorrheic persons are markedly hypoestrogenic (plasma estradiol 10 pg/mL) during the first 180 days postpartum.
• The onset of breast engorgement on days 3-4 of the puerperium coincides with a significant fall in estrogen levels and supports the view that high estrogen levels suppress lactation.
• Prolactin levels in maternal blood rise throughout pregnancy to reach concentrations of 200 ng/mL or more. After delivery, prolactin declines in erratic fashion over a period of 2 weeks to the nongravid range in nonlactating women. In women who are breastfeeding, basal concentrations of prolactin remain above the nongravid range and increase dramatically in response to suckling.
• Serum follicle-stimulating hormone (FSH) and LH concentrations are very low in all women during the first 10-12 days postpartum, whether or not they lactate. The levels increase over the following days and reach follicular phase concentrations during the third week postpartum.
• The time of appearance of the first ovulation is variable, but it is delayed by breastfeeding. Approximately 10-15% of non-nursing mothers ovulate by the time of the 6-week postpartum examination, and approximately 30% ovulate within 90 days postpartum.

Question 36

Phase 3: Cardiovascular System

Answer 36