Obstetrics and Gynecology/Fetal-Placental Physiology of Pregnancy

Introduction
The general objective of pregnancy is to facilitate the nidation, development and maturation, and finally the safe passage of the newborn fetus into the world.

The Placenta
Development of the placenta is described below in The First Trimester.

The placenta functions in maternal-fetal transfer of oxygen, nutrients, wastes, and lastly in hormone production. Significant hormones produced are human chorionic gonadotropin (hCG), and human chorionic somatomammotropin (hPS; formerly known as human placental lactogen).

Transfer of substances across the placental membrane occurs via several fundamental transfer processes: simple diffusion, facilitated diffusion, active transport, and intravesicular transcellular transport.

Human Chorionic Gonadotropin
HCG is a glycoprotein produced in the syncytiotrophoblastic cells of the placenta. It is structurally similar to leutenizing hormone (LH), with an additional 30 amino acids. These additional 30 residues are the basis for the beta-HCG pregnancy test, in order to differentiate B-HCG from LH. Although structurally similar to leutenizing hormone, B-HCG is more potent and has a longer half-life due to resistance to metabolism conferred by carbohydrate inclusion in this molecule.

B-HCG functions to maintain progesterone secretion during pregnancy. Before 6 weeks gestation, this is done at the level of the corpus luteum. After 6 weeks gestation, the majority of progesterone production will take place at the placenta.

B-HCG plays an important role in clinical detection and management of pregnancy. Since it is produced by the syncytiotrophoblastic cells of the developing placenta, it will be detectable very soon after implantation, when a sufficient quantity of syncytiotrophoblast has been developed. The rate of change in B-HCG concentration can be used to track the development of pregnancy. It is generally known that abdominal ultrasound may be used to visualize the developing fetus after B-HCG rises >1500 U/L, and transvaginal ultrasound may be used at concentrations >1000 U/L.

Human Chorionic Somatomammotropin (HCS)
HCS is a polypeptide molecule produced in the syncytiotrophoblast of the developing placenta and secreted almost entirely into the maternal circulation.

HCS functions to maintain the free fatty acid concentrations in the maternal circulation elevated. This action may lead to the development of insulin resistance in the mother and subsequently gestational diabetes. It may be weakly somatotropic, and in keeping with its former name, human placental lactogen, it may also be weakly lactogenic.

Progesterone
Is increased during pregnancy, it causes vasodilation in the maternal blood vessels

Estrogen
Estrogens are produced in both the fetal and maternal bodies: the fetal liver, adrenal glands, and placenta all produce estrogen. The major function of estrogen in pregnancy is thought to be the management of uterine blood flow, a value which becomes elevated to the level of flow to the nulliparous kidneys.

Amniotic Fluid
The amniotic fluid surrounds the developing fetus and lies within the amniotic membrane. It is initially composed of ultrafiltrate, but gradually becomes fluid which is swallowed and respired by the fetus, and urinated back into the amniotic cavity. Typically ~1L of amniotic fluid is produced in the fetal urine per day, which is swallowed, breathed, and transferred intramembranously for establishment of equilibrium.

The First Trimester
First trimester (FT) is from conception to 12-13 weeks.

The significant physiological events occurring in the first trimester are implantation and embryogenesis. This process begins with fertilization of the parental gametes into the euploid zygote. Rapid mitotic divisions transform the zygote into the morula. Continuous mitotic division forms a central cavity within the cell mass which is now termed the blastocyst. The blastocyst contains two cell masses: the outer, which will form the placenta and related supportive tissue, and the inner, which will form the embryo. The blastocyst will implant into the uterine wall within 5-6 days after fertilization.

Placentation
The human placenta begins development at implantation and is completed by the end of the first trimester.

The outer cell mass, or trophoblastic cells will divide into the cytotrophoblast, which forms the anchoring structures for the embryoblast-trophoblast connection, and the syncytiotrophoblast, which is a large, multinucleated, and differentiated syncytial mass of trophoblastic cells which expands outward into the placental parenchyma.

The expanding edges of the syncytiotrophoblast are known as the trophoblastic cords. Blood capillaries grow into these cords from the vasculature of the developing fetus: these cords contain pulsatile flow by the 16th day of gestation! With development of the trophoblastic cords and the chorionic villi, maternal blood sinuses form surrounding these structures: the supplying vessels are the maternal spiral arteries, which will then drain into the uterine veins. As these blood sinuses cannulate, the trophoblastic cords send further projections, the placental villi, to increase the surface area for transfer.

Ultimately the fetal blood will flow to the placenta through two umbilical arteries and back through a single umbilical vein.

During the first trimester, a woman's uterus may grow to being palpable (the upper margin) only a few centimetres below the umbilicus.

The Second Trimester
Second trimester is from the 13th week to the 26-28th week.

The significant physiological events occurring within the second trimester are fetal growth and development.

The Third Trimester
The third trimester is from the 26-28th week until parturition.

Myometrial Activation
During pregnancy, for the most part, the myometrium is quiescent, with the exception of irregularly timed, brief Braxton-Hicks contractions. The uterus in its quiescent state is relatively non-responsive to stimulation of contraction.

Shortly before parturition, the uterus prepares for its endeavour through upregulation of oxytocin and prostaglandin receptors and formation of gap junctions and a functional syncytia. This provides the opportunity to respond to maternal stimuli for the induction of labour.

The Uterine Contractile Apparatus
The uterine myometrium is composed of smooth muscle. Without lengthy discussion of smooth muscle physiology, the final common pathway of smooth muscle contraction is the phosphorylation of the myosin light chain by myosin light chain kinase, which then allows the myosin-actin contractile interactions to occur.

The Excitatory Pathway of Uterine Contraction
Oxytocin and prostaglandins bind to receptors on the uterine smooth muscle cell membranes. Binding activates phospholipase C which subsequently increases intracellular calcium concentrations. This leads to phosphorylation of myosin light chain kinase and activation of myosin-actin interactions.

The Inhibitory Pathways of Uterine Contraction
Beta-adrenergic agonists, acting through G-coupled protein receptors activate adenylate cyclase and subsequently increase cAMP concentrations within the uterine smooth muscle cells. This inhibits myosin-actin interaction.

Furthermore, it has been postulated that nitric oxide and cGMP may inhibit myosin light chain kinase phosphorylation and thus myosin-actin interactions.

The First Stage
The first stage of labour begins with dilation and effacement of the cervix and ends when the cervix is fully dilated.

The first stage is comprised of latent and active stages. The latent stage may not have any time limit. The active phase begins at 4cm dilation or 80% effacement of the cervix. Subsequent cervical dilation should progress at >1.2 cm/h in the primigravid female and at >1.5 cm/h in the parous woman.

The Second Stage
The second stage of labour begins at full cervical dilation and ends with passage of the neonate.

The second stage of labour may be prolonged with administration of epidural anaesthesia.

The Cardinal Movements of Labour
The cardinal movements of labour are as follows:
 * Engagement
 * Flexion
 * Internal Rotation
 * Extension
 * Restitution
 * External rotation

The Third Stage
The third stage of labour begins with birth and ends with passage of the placenta.

This stage typically lasts under 0.5 hours.