Subject
Subject OB-GYN OB-GYN Tranx Tranx No. No. 22
Topic
Topic The Decidua, Placenta,The Decidua, Placenta, and Placental Hormones and Placental Hormones Date
Date 2009 December 142009 December 14 Lecturer
Lecturer Vincent Fortun, MDVincent Fortun, MD Transcriber
Transcriber Ron CortezRon Cortez PagesPages 88 Subject
Subject Head
Head Ronnelaine CortezRonnelaine Cortez
OUTLINE OUTLINE
I.
I. The DeciduaThe Decidua II.
II. The PlacentaThe Placenta III.
III. Placental HormonesPlacental Hormones IV.
IV. Abnormalities of Fetal MembranesAbnormalities of Fetal Membranes
Sources: Past Tranx, Williams Obstetrics, and Recordings Sources: Past Tranx, Williams Obstetrics, and Recordings
A.
A.
The DeciduaThe Decidua
Highly specialized and modified endometrium of pregnancyHighly specialized and modified endometrium of pregnancy
B.
B.
Functions of the Functions of the Decidua:Decidua: 1.1. Facilitates apposition and implantation of the Facilitates apposition and implantation of the blastocystblastocyst 2.
2. Serves as an Serves as an immunologically specializeimmunologically specialized tissued tissue 3.
3. Accepts trophoblast invasion, thus providing for embryo-fetal nutritionAccepts trophoblast invasion, thus providing for embryo-fetal nutrition 4.
4. Contributes cytokines and growth factors that promote Contributes cytokines and growth factors that promote placental growth, function, and the inhibition of placental growth, function, and the inhibition of trophoblast apoptosis
trophoblast apoptosis
C.
C.
Structure of the DStructure of the Decidua: ecidua: (Must-know term(Must-know terms)s) 1.1. Decidua basalisDecidua basalis – –the portion directly beneath the sitethe portion directly beneath the site of blastocyst implantation
of blastocyst implantation 2.
2. Decidua capsularisDecidua capsularis – –the portion overlying the enlargingthe portion overlying the enlarging blastocyst
blastocyst 3.
3. Decidua parietalisDecidua parietalis – –the portion covering the remainderthe portion covering the remainder of the uterus
of the uterus
D.
D.
Layers of the Layers of the Decidua:Decidua: 1.1. Zona compactaZona compacta – –surface of the deciduasurface of the decidua 2.
2. Zona spongiosaZona spongiosa – –the middle portion of the deciduathe middle portion of the decidua 3.
3. Zona basalisZona basalis – –remains after delivery and gives rise remains after delivery and gives rise toto the new endometrium
the new endometrium (Favorite board question)(Favorite board question) *Zona functionalis = zona compacta
*Zona functionalis = zona compacta + zona spongiosa+ zona spongiosa
*May also be referred to as stratum compacta, stratum spongiosa, and so on. *May also be referred to as stratum compacta, stratum spongiosa, and so on.
E.
E.
Vascular SupplyVascular Supply
The spiral arteries of the deciduThe spiral arteries of the decidua are a very prominent organ/structure. a are a very prominent organ/structure. They arise from the arcuate arteriesThey arise from the arcuate arteries
which are branches of the uterine vessels.
which are branches of the uterine vessels. These are the high-pressure blood vessels bringing oxygeThese are the high-pressure blood vessels bringing oxygenatednated blood to the decidua.
blood to the decidua.
The ovarian and endometrial cycles’ The ovarian and endometrial cycles’ specific modificationspecific modifications in the rate of blood flow in s in the rate of blood flow in these arteries arethese arteries are
essential for: essential for: 1.
1. The initiation of menstruationThe initiation of menstruation 2.
2. The limitation of blood loss in the mensesThe limitation of blood loss in the menses
F.
F.
MenstruationMenstruation
Menstrual bleeding is of botMenstrual bleeding is of both arterial and venous origin. h arterial and venous origin. ((But arterial bleeding is, But arterial bleeding is, quantitatively, appreciably quantitatively, appreciably
greater than venous.) greater than venous.)
Batch 2012 / 2009-2010 Batch 2012 / 2009-2010
I.
G.
Physiology of How Menses Occur:rhexis or rupture of an arteriole of a spiral artery hematoma formation
superficial endometrial distention and rupture fissures develop in the adjacent functional layers
blood and tissue are detached or sloughed off appearance of menstrual blood in the vagina
Supplies all materials required for fetal growth and energy production while removing products of fetal
catabolism. Provides nutrition and takes care of waste products during the pregnancy.
Provides much insight into prenatal life
Results of its examination are often helpful in caring for the neonate. (So it’s important for pediatricians as
well.)
Gives a record which pediatricians and obstetricians can use to plan for the future care of the mother and the child.
The placenta has two sides:
1. Fetal side – smooth, shiny, and relatively free of blood 2. Maternal side – bloody, dark red, with lobes and cotyledons
HEMOCHORIOENDOTHELIAL PLACENTATION
o Unique to humans
o At all sites of direct cell-to-cell contact, maternal tissues (both eciduas and blood) are juxtaposed
(closely attached) to extraembryonic cells (trophoblasts) and NOT to the embryonic cells or fetal blood.
o There is no mixing of fetal and maternal blood. Otherwise, problems will occur. There is always an
intervening structure.
o Maternal blood in the intervillous space directly bathes the trophoblasts. Transfer of substances
(oxygen, nutrients) from mother to fetus is accomplished first by transfer from the intervillous space
into the syncytiotrophoblast. There’s no direct transfer from maternal to fetal blood.
A. EARLY HUMAN DEVELOPMENT (Review)
(Take note of the chronology. Again, common board exam question.)
Fertilization of the egg by a spermatozoan occurs in the fallopian tube. A common misconception is that
fertilization occurs in the uterus.
The mature ovum becomes azygote (a diploid cell with 46 chromosomes). Zygote undergoes cleavage to form blastomeres.
Sixteen or so blastomeres form a solid ball called morula (3rdto 4thday after fertilization takes place). The blastocyst is formed after the morula reaches the uterus (usually 6-7 days after fertilization), with the
formation of a fluid-filled cavity within it.
The inner cell mass gives rise to the embryo.
Embryonic period lasts until the end of the 7thweek.
After embryonic period, the developing conceptus is referred to as the fetus.
*Remember: Before 7 weeks AOG = embryonic period
After 7 weeks AOG = the conceptus is now called the fetus
1. IMPLANTATION
The blastocyst adheres to the endometrium of the uterus. (~7 days after fertilization) The implanting blastocyst becomes completely buried in and covered by the endometrium.
2. TROPHOBLAST
A very specialized cell, Dr. Fortun’s favorite cell:“ Without it, you and I would not be here.” Responsible for implantation
Its invasiveness provides for attachment of the blastocyst to the uterus. Role in nutrition of the conceptus
Endocrine function is essential to maternal physiological adaptations and the maintenance of pregnancy 2 kinds: Cytotrophoblast and Syncytiotrophoblast
Becomes the bane of women in trophoblastic cancer.
CYTOTROPHOBLAST SYNCYTIOTROPHOBLAST
- Well-demarcated borders - Single, distinct nucleus - Frequent mitosis
- Cellular progenitors of the syncytiotrophoblasts
- Produce cellular enzymes which allow it to move between and attach to endometrial epithelial cells during blastocyst
implantation. - Pale-staining
- No cell borders
- Nuclei are multiple and diverse in size and shape
- Amorphous cytoplasm
- Controls transport processes across the synctia (very important for fetal nutrition) - Secretes hormones (most important
function)
- Very dark-staining because of very high nuclear activity
*How come the developing embryo is able to attach itself into the endometrium of the mother when 50% of its DNA is foreign? Normally, when there is something foreign that enters our body, our immune system tends to destroy that foreign body. The wonder of pregnancy is in the immunologic acceptance of the fertilized ovum.
B. IMMUNOLOGIC ACCEPTANCE OF THE CONCEPTUS
Human Leukocyte Antigen-G (HLA-G) is expressed exclusively by cytotrophoblasts, and is monomorphic (“self”); thus, does not evoke an immunological response by maternal immune cells against fetal
trophoblasts.
The regulation of HLA-G Class I antigen expression on extravillous cytotrophoblasts may be crucial in first
allowing, and then inhibiting cytotrophoblast invasion of the endometrium/decidua and spiral arteries.
C. PLACENTAL DEVELOPMENT
After blastocyst implantation, cytotrophoblasts proliferate rapidly and invade the surrounding decidua. Anchoring and villous trophoblasts form the early placenta.
Walls of superficial decidual capillaries are eroded and the walls of spiral arteries are destroyed. (The fertilized ovum is a “parasite”, so it has to find source of nutrition and oxygen for it to survive. Hence, the
trophoblasts now seek out these capillaries/arteries.)
Maternal blood directly bathes the syncytiotrophoblasts in the intervillous space (14thto 15thday of life). MUST-KNOW!
Villi in contact with the decidua basalis proliferate to form the chorion frondosum (the fetal component of the
placenta).
Villi in contact with thedecidua capsularis degenerate to form the chorion laeve.
After the 3rdmonth, the chorion laeve and the amnion come into contact and form the amniochorion/fetal
membranes.
D. PLACENTAL BARRIER
Substances that pass from maternal to fetal blood must first traverse:
1. Syncytiotrophoblast
2. Stroma of the intravillous space 3. Fetal capillary wall
However, the placenta does not maintain absolute integrity of the fetal and maternal circulations at times
such as in cases of erythroblastosis fetalis.
E. PLACENTA AT TERM
185 mm in diameter 23 mm in thickness 497 ml average volume 508 g weight
10 to 38 cotyledons (cotyledons separated by septae) F. PLACENTAL AGING
Decreased thickness of syncytium
Formation of syncytial knots (stroma within the placenta) Villous stroma, Hobauer cells, and Langhans cells are reduced
Thickening of the basement membranes of the capillaries and trophoblasts (very important because if there’s thickening of the basement membrane, there is less amount of oxygen and nutrients that can reach placental circulation)
Obliteration of certain fetal vessels
Deposition of fibrin on the surface of villi, basal and chorionic plates, and intervillous space
*The placenta degrades as the pregnancy nears term, t his is why we don’ t want post-term babies (>42 weeks AOG)
G. FETAL CIRCULATION (Must memorize)
Fetal deoxygenated blood flows to the placenta through thetwo umbilical arteries.
At the juncture of the umbilical cord with the placenta, the umbilical vessels branch repeatedly (chorionic
arteries to truncal arteries) to form capillary networks in the terminal divisions of the villi.
Blood with a higher oxygen content returns from the placenta to the fetus through a single umbilical vein.
Common Evals/Board Exam Questions:
Which blood vessel has a higher oxygen content: the umbilical vein or the umbilical artery? How many umbilical veins are there?
How many umbilical arteries?
H. MATERNAL CIRCULATION
Maternal blood enters the intervillous space in spurts produced by maternal blood pressure. Blood is then forced toward the chorionic plate.
Lateral spread of blood occurs.
Arterial pressure forces blood toward exits in the basal plate to the uterine veins
During uterine contractions, both inflow and outflow are curtailed, while the volume of the blood in the intervillous space is maintained; thus, providing for continuous exchange.
Even if the uterus is contracting vigorously during labor, there is still an adequate amount of blood within the placenta to maintain constant exchange of nutrients and waste products between maternal and fetal blood.
I. ABNORMALITIES OF PLACENTATION (Definitions from Williams Obstetrics, 22nd ed.)
Multiple placentas with a single fetus - The placenta occasionally is separated into lobes. When the division
is incomplete and the vessels of fetal origin extend from one lobe to the other before uniting to form the umbilical cord, the condition is termed placenta bipartita or bilobata. If the two or three distinct lobes are separated entirely, and the vessels remain distinct, the condition is designated placenta duplex or placenta triplex.
Succenturiate placenta - An extra placenta separate from the main placenta. In anatomy, "succenturiate"
means substituting for or accessory to an organ. In this case, a succenturiate placenta is an accessory placenta.
Ring-shaped placenta - the placenta is annular in shape, and sometimes a complete ring of placental tissue
is present. Because of tissue atrophy in a portion of the ring, a horseshoe shape is more common.
Membranous/Membranaceous placenta - Very rarely, all of the fetal membranes are covered by
functioning villi, and the placenta develops as a thin membranous structure occupying the entire periphery of the chorion. This finding is called placenta membranacea and also is referred to as placenta diffusa.
Fenestrated placenta - In this rare anomaly, the central portion of a discoidal placenta is missing. In some
the chorionic plate intact. Clinically, it may be mistakenly considered to indicate that a missing portion of placenta has been retained in the uterus.
Extrachorial placenta - A placenta in which there is a rim of placental tissue that extends beyond the
vascular plate, accompanied by fibrin on the margin.
Large/Mega placenta Placental polyp
J. PLACENTA: CIRCULATORY DISTURBANCES
Infarcts Calcification
Villous (fetal artery thrombosis)
K. THE AMNION
Identifiable at the 7thto 8thday of embryonic development
The innermost fetal membrane (contiguous with the amniotic fluid)
Provides almost all of the tensile strength of the fetal membrane (Evals Question) Does not contain smooth muscles, nerves, lymphatics, and blood vessels.
o Used as biological dressings since the tensile strength is good and no other structures are prone to
degradation 1. Development of the Amnion
At the 7thor 8thday of embryonic development, the amnion develops into a small sac that covers the dorsal
surface of the embryo. Amnion enlarges and covers the whole embryo Comes into contact
with the interior surface of the chorion laeve Apposition of the chorion laeve and amnion causes
obliteration of the extraembryonic coelom 2. Layers of the Amnion
Epithelium
Basement membranes Compact layers
o Responsible for tensile strength
Mesenchymal cell layer Zona spongiosa
3. Metabolic Functions of the Amnion
Transports solutes and water to maintain amniotic fluid homeostasis Produces vasoactive peptides (no need to memorize)
o Endothelin-1
o Parathorome-related protein o Enkephalinase
o Brain natriuretic peptide
o Cortocotropin-relaxing hormone
Secretes growth factors and cytokines
4. Amniotic Fluid
Clear
Increases in quantity as pregnancy progresses till near term Average volume: 1,000 mL
In early pregnancy, it is an ultrafiltrate of maternal plasma.
By the 2ndtrimester, it consists largely of extracellular fluid which diffuses through the fetal skin. After 20 weeks, it is composed largely of fetal urine.
Pulmonary fluid and fluid filtering through the placenta also contribute.
5. Chorioamnionitis
Inflammation of the fetal membranes
Mononuclear and polymorphonuclear leukocytes infiltrate the chorion (a pathologic diagnosis) Managed by antibiotics and immediate delivery (otherwise, the baby will have sepsis)
L. THE UMBILICAL CORD
Extends from the fetal umbilicus to the fetal surface of the placenta (chorionic plate). Dull white, moist, covered by amnion
0.8 to 2.0 cm in diameter 55 cm in length
“False knots” are varices caused by folding and tortuosity of the blood vessels
The umbilical vein carries oxygenated blood to the fetus. The right umbilical vein disappears as it
develops.
The two umbilical arteries carry deoxygenated blood from the fetus to the placenta.
The production of steroid and protein hormones by human trophoblasts is greater in amount and diversity than
that of any endocrine tissue known in all mammalian physiology or pathophysiology. A. HUMAN CHORIONIC GONADOTROPIN (hCG)
“pregnancy hormone”
A glycoprotein structurally related to and with biological activity very similar to Luteinizing Hormone (LH),
Follicle-Stimulating Hormone (FSH), and Thyroid-Stimulating Hormone (TSH)
Produced almost exclusively in the placenta specifically by syncytiotrophoblasts Produced by malignant tumors (trophoblastic cancers)
Produced in small amounts by the anterior pituitary glands of both men and women. Nobody knows why
even men produce hCG. 1. Molecular Forms of hCG
Intact hCG molecule
o Rate of secretion is maximal at 8 to 10 weeks of pregnancy. After that, its level slowly goes
down but even if it goes down, it does not go back to normal.
Beta subunit
o most important because it is easily measurable by present-day technology. Free alpha,
nicked hCG, and beta-core fragment are very difficult to measure.
Free alpha subunit Nicked hCG molecule Beta-core fragment of hCG
2. hCG Concentrations in Pregnancy
hCG enters maternal blood at the time of blastocyst implantation (about 7-9 days post-ovulation Concentration in the maternal plasma is equal to the concentration in maternal urine
o Before the advent of urine testing, we used to determine if a woman is pregnant by getting
a blood sample.
1,000 mIU/mL = 6 weeks of pregnancy
100,000 mIU/mL = 8 to 11 weeks of pregnancy
Concentrations in the plasma start to decline at 10 weeks (nadir at 20 weeks) In normal single pregnancies, the level should not go beyond 100,000 mIU/mL
3. Conditions with Elevated hCG levels (>100,000 mIU/mL)
Pregnancies with multiple fetuses Erythroblastotic fetus
Syphilis in pregnancy
H-mole or choriocarcinoma Fetus with Down Syndrome
Non-trophoblastic tumors (germ cell tumors)
4. Conditions with Depressed hCG levels
Ectopic pregnancy
Impending spontaneous abortion Death of fetus
5. Biologic Functions of hCG
“rescue”and maintenance of function of the corpus luteum –MOST IMPORTANT Stimulation of fetal testicular testosterone secretion
o Promote male sexual differentiation –Were it not for hCG, all of us would be females
Stimulation of maternal thyroid gland
Promotes relaxin secretion by corpus luteum
B. HUMAN PLACENTAL LACTOGEN (hPL)
Concentrated in syncytiotrophoblasts (5 weeks) Maximal concentrations at 34-36 weeks
Rate of secretion is proportional to placental mass
o Low levels in trophoblastic disease patients
Also secreted by malignancies other than that of trophoblast or of gonad
o Bronchogenic Ca, hepatoma, lymphoma, pheochromocytoma
Metabolic Functions of hPL
Lipolysis and increased levels of free fatty acids
o Provides source of energy for m aternal metabolism and fetal nutrition
Anti-insulin action
o Increased maternal insulin levels favors protein synthesis for transport to the fetus.
C. ESTROGEN
Human pregnancy is an hyperestrogenic state Syncytiotrophoblast secretes two estrogens:
o Estradiol-17 Beta o Estriol
Promotes growth of the endometrium
D. PROGESTERONE
Produced by syncytiotrophoblast
Facilitates and permits the maintenance of pregnancy
Formation occurs through the uptake and use of maternal LDL cholesterol
E. OTHER PROTEIN HORMONES OF THE PLACENTA (No need to memorize)
Chorionic Adenocorticotropin Chorionic Thyrotropin
Hypothalamic-like Releasing Hormones Relaxin
o Promotes uterine relaxation
Parathyroid Hormone-related Protein
o PTH of fetus
Human Growth Hormone-Variant
o Biological activity similar to hPL
Neuropeptide-Y Inhibin
o In conjunction with sex steroids, may serve to inhibit FSH secretion during pregnancy (no ovulation)
Activin
Atrial Natriuretic Peptide
Review: The amniotic fluid, in early pregnancy, is an ultrafiltrate of maternal plasma. By the 2ndtrimester, it consists largely of extracellular fluid. After 20 weeks, it is composed largely of fetal urine.
A. MECONIUM STAINING
Meconium
o The first material excreted by the fetus via the anus.
o Composed of exfoliated gastrointestinal tract cells of the fetus
o However, if in the time of birth, when the baby takes his first breath and aspirates the
meconium, it can cause irritation of the fetal lungs.
Occurrence increases after 40 weeks AOG
Passage is associated with increased perinatal morbidity and mortality due to meconium aspiration
B. CHORIOAMNIONITIS
Inflammation of the fetal membranes A manifestation of intraamnionic infection
Frequently associated with prolonged membrane rupture and prolonged labor Treatment: antibiotics and immediate delivery
C. HYDRAMNIOS
Amniotic fluid of >2,000 mL volume
Amniotic fluid index of >24 cm (via ultrasound)
Presence is associated with fetal malformations, especially of the central nervous system (e.g.,
anencephaly, spina bifida) or gastrointestinal tract (e.g., esophageal atresia); and in monozygotic twin pregnancies
Symptoms result from pressure exerted within and around the overdistended uterus upon the adjacent
organs.
The more severe the degree of hydramnios, the higher the perinatal mortality rate; causes fetal
malformations, chromosomal abnormalities, preterm labor
Maternal complications: o Placental abruption o Uterine dysfunction o Postpartum hemorrhage Management: o Amniocentesis o Amniotomy D. OLIGOHYDRAMNIOS
Amniotic fluid index of 5 cm or less Fetal outcome is poor
Conditions associated:
o Fetal –chromosomal abnormalities, post-term pregnancy o Placental –abruption, twin-twin transfusion
o Maternal –hypertension, preeclampsia, diabetes in pregnancy o Drugs –prostaglandin synthetase inhibitors
o Idiopathic
Management:
o Amnioinfusion during labor (adding more amniotic fluid into the sac) –not done in UMC as it is
very complicated
o Abdominal delivery –It depends. Among obstetricians, if they see an oligohydramnic mother
who is less than 5cm dilated, they usually deliver abdominally. But if the mother is 7-9 cm dilated, they still opt for a vaginal delivery with close monitoring.
-END OF TRANSCRIPTION-Those with are the ones Dr. Fortun gave importance to in the lecture