Repro 3 Pregnancy, Labor, Delivery Flashcards
What comprises the placenta components?
►Umbilical Cord
►Placenta Membranes (adhered) •Amnion – closest to fetus – translucent •Chorion – closet to uterus
►Placental Disc
– Fetal Surface
– Maternal Surface
– Parenchyma (villus tissue)
Umbilical Arteries
…vs…
Umbilical Veins
What do they carry?
Umbilical Arteries (2)
– away from fetus
– deoxygenated
Umbilical Veins
– from mom to fetus
– oxygenated
– nutrient rich
How is the umbilical cord inserted in the placenta?
►Centrally Insertion
►Eccentrically Insertion
– 90% of cases
► insertion within 1 cm of the disc margin
– 7% of cases
►Velamentous Insertion
– inserts into the placental membranes
– 2% of cases
– vessels of the cord run the final distance to the disc through the membranes, unsupported by the Wharton’s jelly.
Velamentous Cord Insertion
What is the clinical impact?
Velamentous Insertion
have been associated with reduced fetal growth and risk of rupture of the fetal vessels
Amnion
- develops from the inner cell mass
- eventually covers umbilical cord, fetal surface of the placenta and creates the amniotic sac around the fetus
- expands out to eventually meet the chorion, with the membranous sac containing the amniotic fluid and developing fetus.
Amnion
Histology
• multilayered with cuboidal epithelium lying on a well-defined BM, deep to which are the compact, fibroblast and spongy layers
Chorion
- develops from the chorionic villi on the side of the chorionic sac that is expanding into the uterus
- These villi degenerate leaving the smooth chorion that eventually expands to fuse with the decidua parietalis on the side of the uterus opposite the implanted embryo.
- The chorion is also multilayered comprising cellular and reticular layers, pseudomembrane and trophoblast
How long do the amnion & chorion grow for?
- Grow until 28 weeks gestation, after which time mitotic activity is rare.
- Enlargement of the sac after this date is by stretching
Normal Placental Membrane
…vs…
Abnormal Placental Membrane
Appearance?
►Normal Placental Membrane
– clear membranes
– non-cloudy
►Abnormal Placental Membrane
– Greenish-Black staining → suggests meconium (fetal stool) passage inutero related to fetal stress (loss of anal sphincter tone)
– Greenish-Yellow → suggests ascending infection.
How does placenta size compare with fetal size?
Placenta increases in size throughout gestation, and remains larger than the fetus until ~16 weeks
Placenta size at birth
~500 grams
2-3cm thick
15-20cm in diameter
►Fetal Surface
…vs…
►Maternal Surface
►Fetal Surface
– comprises fetal surface vessels displaying an arborising pattern, spreading out from or draining to the umbilical cord
– may have vessel thrombosis
►Maternal Surface
– beef red color
– does not normally display organized clot
– divided into discrete lobules or cotyledons, that should be assessed for completeness at the time of delivery.
What does the maturation process of the Placenta include?
- increased SA for exchange
- closer approximation of maternal and fetal circulations
- increased uterine blood flow.
What is the functional unit of maternal-fetal exchange?
►placental villi
- Throughout gestation the villi become increasingly branched from stem villi → intermediate villi → terminal villi
- terminal villi comprise greater than 50% of the villous SA and are the major site of maternal-fetal exchange
How does uterine blood flow increase throughout pregnancy?
►Increased Amount
• Uterine blood increases 10X throughout the pregnancy, reaching >700cc/min near term.
►Increased Distrubution
• As pregnancy progresses, a greater proportion of the uterine blood flow is directed away from the endometrium and myometrium and towards the placental cotyledons.
• Near term over 90% of the uterine blood flow is to the placenta (initially as a result of increased number of vessels and later in gestation from increased vasodilatation).
Why must the uterus contract down after pregnancy?
After delivery the uterus must contract down on the uterine vessels that were supplying the placenta, in order to prevent maternal hemorrhage.
At a normal vaginal delivery, a mother might lose up to 500cc of blood, but if the uterus fails to contract, it cat take only minutes at a flow rate of 700cc/min for a mother to exsanguinate.
1st Trimester Placental Villi
Maternal and fetal blood separated by 3 cell layers: • syncytiotrophoblasts • cytotrophoblast • fetal capillary endothelium
- large villi, covered in 2 layers of cells (cytotrophoblasts and syncytiotrophoblasts)
- few centrally located vessels
- abundant loose stroma
3rd Trimester Placental Villi
- Villi become more branched and vascular
- Fetal vessels move to a more eccentric location
- Cytotrophoblasts degenerate so maternal and fetal blood are separated by 2 cell layers: (syncytiotrophoblasts and fetal capillary endothelium)
- decreased distance between maternal and fetal circulations
- As a result, there can be some interaction between mom & baby blood in later pregnancy
As a placenta matures and increases in size, the villi become smaller and highly vascular. The fetal vessels move to a more eccentric location.
The cytotrophoblasts degenerate leaving a single syncytiotrophoblast layer in close proximity to the fetal capillary endothelium. Fusion of fetal capillaries and the syncytiotrophoblast occurs in the 3rd trimester, developing a vasculosyncytial membrane (VSM).
In some areas the syncytiotrophoblasts draw up into “syncytial knots” which can be seen on microscopy of the 3rd trimester placenta. The overall effect is a significantly decreased distance between the maternal and fetal circulations.
Villus Tissue
Most of the placental disc comprises placental villous tissue: the functional unit involved in transfer between mother and infant.
The villus comprises fetal vessels within its core, and is surrounded by blood from the maternal circulation.
The villous tissue is organised in 3 types of villi.
What are these types?
(1) The stem villi are identified by the presence of vessels with a clearly visible media on light microscopy. They attach firmly to the decidua basalis to anchor the chorionic sac.
(2) The intermediate villi arise from the stem villi. They contain reticular stroma and vessels without demonstrable media on light microscopy.
(3) The terminal villi are the functional unit of fetomaternal exchange. They represent the final branches of the villous tree of the placenta.
What are factors that may modify the maturation process of the placenta?
►Maternal nutrition ►Altitude ►Exercise ►Maternal disease: – DM – Alchohol – Smoking – HTN (vasoconstriction and reduced blood flow to uterus and placenta)
►pregnancy progressing beyond term
What is the risk in allowing a pregnancy to progress post-term?
The placenta reaches maximum size and villus SA at 37 wks gestation, therefore pregnancy progressing beyond is met with a decrease in placental fx.
If the fetus continues to grow, the placenta-fetus ratio decreases and nutrient transfer is compromised.
Increased perinatal morbidity and mortality
EVERY placenta should be examined grossly after delivery.
In certain situations a pathologist should be involved.
How can indications for detailed exam can be grouped?
►Maternal/obstetrical
►Fetal/neonatal
►Placental
►Maternal/obstetrical
Indications for Pathologist Review of Placenta:
►DM
►HTN
►Prematurity (42 weeks)
►Hx of reproductive failure (recurrent miscarriages, stillbirth, neonatal death, premature births)
►Oligohydramnios (low amniotic fluid volume)
►Maternal fever
►Maternal substance abuse
►Repetitive maternal vaginal bleeding (excluding minor spotting in first trimester)
►Placental abruption (premature separation of the placenta)
►Fetal/neonatal
Indications for Pathologist Review of Placenta:
►Stillbirth or perinatal death ►Multiple birth ►Congenital abnormalities ►Fetal growth anomaly ►Prematurity (<32 weeks) ►Fetal hydrops ►Meconium stain of the amniotic fluid ►Admission to neonatal ICU ►Severe respiratory depression at birth ►Neurological problems including seizures
►Placental
Indications for Pathologist Review of Placenta:
Any gross abnormality …
►disc
(eg. placental infarct)
►membranes
►cord
(eg. knot)
Gross Examination of Plancenta
What do we examine?
(1) Umbilical Cord
(2) Membrances
(3) Placental Disc
(1) Umbilical Cord
►Length and diameter.
►Insertion and vessel count
►Varicosity, false and true knots.
►Areas of engorgement, torsion or deficiencies of Wharton’s jelly, and changes of coloration.
(2) Membranes
►Coloration
►Point of Rupture:
Its position is important in relationship to the placenta and the blood vessels, especially if some blood vessels travel on the membranes unprotected. Damage to one of the fetal blood vessels could lead to loss of fetal blood, and potentially hypovolemia, shock or death for the fetus.
►Membrane Insertion onto Placental Disc
• Normal membrane insertion → into margin of placental disc.
• Circumvallate Placenta → usually has no clinical significance, though may be associated with antepartum hemorrhage, growth restriction and prematurity
(3) Placental Disc
EXAMINE FOR …
►Contour
►Accessory lobes
►Dimensions and trimmed weight (after removing the cord and membranes)
• The size of the placental usually correlates well with the size of the fetus. A small or underdeveloped placenta could be associated with less than optimal placental fx. A placenta too large for the fetal size could be associated to pathologies such as perinatal infection (i.e. viral infection).
►Fetal surface: vascular pattern, thrombi, cysts, plaques
• The fetal surface (the one facing the fetus) should be showing an arborised vascular pattern. A lesser degree of arborisation could potentially lead to a lesser uptake potential from the placenta. Lesions representing obstructions of the fetal vasculature (such as thrombi) can also explain signs of lesser uptake from the fetus (such as fetus smaller than expected for gestational age).
►Maternal surface: completeness, fibrin, calcification, infarction
• Areas of induration, discoloration or calcifications can be associated with vascular accidents in the placenta, also potentially compromising its function.
►Cut surface: infarcts, fibrin, gross abnormality
• By cutting through the placenta, the pathologist can assess the body of the placenta rather than just the fetal and maternal surfaces.
What is a succenturiate lobe?
succenturiate = “accessory”
Majority of placentas are a single circular disc. However, some may have an accessory “succenturiate” lobe.
Assessment of the contour and completeness of the placental disc may raise suspicion of retained portions of placenta which increase the risk of postpartum hemorrhage and infection.
What can contribute to a small baby?
►Prematurity
►Smoking
►Maternal Disease
►Infection
►Genetic (eggs & chromosomal abnormalities)
►Constitutional
►Placental → A significant proportion of growth restricted fetuses are due to placental issues
Human placenta is a unique organ as it is formed from 2 genetically distinct people (mom & fetus)
“Hemochorial”
What do we mean by this?
►“Hemochorial”
– maternal blood in direct contact with fetal trophoblasts
The endometrium is only receptive to a blastocyst for a short time
What is the time range?
What is the hormone that facilitates it?
8-10 days post LH surge
6-7 days post fertilization
Correlates with the high circulating level of Progesterone (“pro-gestation”)
What does Implantation require?
►Requires 2 synchronous processes:
– Uterine preparation (decidual reaction)
– Embryo dvpt and ability to interact with endometrium
NOTE: 50% of all conceptions fail at this critical time of implantation
– Many have abnormal karyotype
– IVF higher failure rate likely due to issues with implantation
“The red carpet welcome”
describes the changes to the endometrium that occur to “welcome” a blastocyst.
What are they?
►Morphologic – Increase cell size – change in cell shape – extensive development of intracellular organelles for protein synthesis and secretion – formation of intracellular junctions
►Functional: lipid and glycogen accumulation for energy
What is the decidua?
3 distinct layers
►Decidua parietalis
– Non-implantation site
►Decidua capsularis
– Thin capsule of endometrium covering the developing embryo
►Decidua basalis
– Implantation site
– Eventually becomes the maternal portion of the developing placenta
►Decidua parietalis
►Decidua capsularis
As the embryo grows, it expands into the urine cavity. These two “decidua” join to form …
decidua vera
Where does the placenta usually implant?
►Usually implants in fundus (most muscular & vascularized region)
►Implant over cervix
– “placenta previa”
– can bleed
– will require C-section
►Other sites
– ectopic
– outside uterus
Where does fertilization typically occur?
Ampulla of Fallopian Tube
Trophoblasts are outer cell mass of blastocyst
These cells are destined to become 2 cell types. What are these?
►Cytotrophoblasts:
– progenitor cells
– Villus cytotrophoblasts
– Extravillus cytotrophoblasts
►Syncytiotrophoblast
– Giant, multinuclear cells formed by fusion of cytotrophoblasts (finger-like projections)
– like a glove for the finger-like cytotrophoblastic projections
– Terminally differentiated
– Invasion into endometrium
Lacunae start to form.
What are they?
What are their function?
Lacunae are little spaces that will soon swell up with maternal blood.
When does the placenta first begin to function?
At about 21 days
This is when embryo will start to draw resources from mom
This is the point that mom’s blood & baby’s blood begin to exchange products.
How does the maternal blood encounter the fetal blood?
Maternal blood hits the chorionic plate and percolates back to exchange with fetal blood
Why is the process of spiral artery invasion so critical to the development of the maternal circulation in the placenta?
Remodeling of the spiral arteries converts a tight, thick walled, muscular vessel into an open, capacitance vessel that can accommodate the tremendous increase in maternal blood flow required to adequately nourish the placenta and fetus.
More about this in Histo notes
These Spiral Arteries are critical!
What is the clinical implication of the placenta not allow adequate blood
If the placenta does not allow adequate blood then we risk having pre-term birth, growth restriction lack of O2 … but also affects mom by increasing risk of Pre-ecclampsia
This may be destined at 32 weeks to have a baby that does not grow as well.
Cytotrophoblasts are supposed to got to inner 3rd of myometrium.
The spectrum of abnormalities arise from invasion that ranges from too shallow to too deep.
What is the clinical consequence of invasion that is too shallow?
►Growth restriction
►Prematurity
►Abruptio placenta
– mat effects: bleeding can induce labor
– fetal effects: demise
►Preeclampsia (HTN)
►Stillbirth
What is the clinical consequence of invasion that is TOO deep?
Pathologic deep invasion
(accreta spectrum)
►Placenta accreta
–too far
►Placenta increta
– even farther!
►Placenta percreta
– invades into the serosa
– placenta may not separate!
– invasion SO far that we have to perform hysterectomy at delivery)
RISKS:
• Maternal morbidity of bleeding
• Fetal risks of bleeding & prematurity
Pathologic deep invasion
(accreta spectrum)
Risk Factors?
►Prior C-section or uterine surgery (fibroid removal - huge tumor of muscle)
– Uterine scar becomes a site of uncontrolled invasion
►Placenta previa
– implanted near cervix
– Lower uterine segment implantation more likely to have deep invasion
►Previa PLUS prior uterine surgery
– Biggest Risk!
– C-section scar is not a good spot for future implantation!
– One prior C-section and current previa = 25 % risk accreta
– 2 prior C-section and current previa = 40% risk accreta
Placental implantation is an important concept.
Accretas are often undiagnosed until delivery when you are unable to deliver the placenta.
What is the clinical implication?
– postpartum hemorrhage
– hysterectomy
– maybe even death
Maternal death with accreta reported up to 7%
How can a Doppler be used to investigate placental Invasion?
Normally, any muscular artery should a sharp spike followed by “notch” and shallow diastolic wave. This would indicate that the elastic recoil is intact.
However, spiral arteries of the placenta should be opened up and no longer have this “notch.”
►Good spiral artery invasion
– we do not want to see elastic recoil
– we want to get rid of the musculature and have lots of diastolic blood flow
►Shallow invasion
– tight muscular spiral arteries
– “notch” retained
– good for other arteries, but not for placenta!
– we cannot treat it, but we should monitor Mom’s BP and consider this a high risk preg.
What is the medical recommendation of where to deliver?
Medical recommendation is to deliver in hospital.
Now … if the mom has had a prior C-section, this raises the risk of Accreta. We can’t detect this until delivery. Therefore, the medical recommendation REALLY is to deliver in hospital.
Again, what are the two red flags that tell us a woman REALLY should deliver in hospital?
►Placenta Previa (over cervix)
►C-Section (prior uterine surgery)
The placenta actually uses more energy than the fetus
Crazy, but true
Here are the details …
1/2 of O2 and 2/3 of glucose delivered to the uterus is used by the placenta for:
►Energy storage: placenta synthesizes glycogen, which it stores as an energy reserve
►Production: of proteins and steroids
►Transport: active transport of some elements requires energy
TRUE or FALSE?
The placenta can autoregulate it’s blood flow
FALSE!
Because the maternal blood is in the intervillous space and not within vessels, there is no way to autoregulate the blood flow within the placenta
– Cannot vasoconstrict or vasodilate to alter blood flow
– The regulation of flow is based on maternal CO, BP and SA of the functional unit (i.e. resistance)
RESULT: A key determinate of fetal oxygenation is the maternal uterine blood flow = CO
Why are pregnant women told NOT to lie flat on their backs?
The uterus gets to be really bog and heavy. When lying flat on back the uterus can compress the vena cava and reduce venous return to the heart.
RESULT: CO drops
SO: Lie on side to take weight off
What crosses by simple diffusion?
Compounds that are essential for min-to-min homeostasis of the fetus
- Oxygen
- CO2
- Water
How does glucose cross?
GLUCOSE
• Placenta does not produce glucose until late gestation, so uptake of maternal glucose is essential
• Favorable gradient from mother to fetus
• Facilitated diffusion with glucose receptors on the
• Non-energy dependent
• Non-insulin dependent
• This process is even more efficient than simple diffusion alone at ensuring adequate glucose supply to the fetus
What change occurs in mom to enable glucose delivery to fetus?
Pregnancy itself is a relative state of insulin resistance.
This enables serum glucose to be higher so that there is a gradient by which glucose preferentially goes to fetus.
NOTE: If mom already has a predisposition to DM type 2, the relative insulin resistant state of pregnancy may be enough to “push” her over the edge into Gestational Diabetes. Thus, pregnancy unmask DM risk.
What is moved by Active Transport?
►AMINO ACIDS
• fetus need a LOT!
• Used for protein synthesis and energy source
• Large molecule
• must move aa against gradient as fetus has a higher conc of aa relative to mother
►LACTATE
• large amounts of lactate produced by placental metabolism are transferred to maternal circulation
Endocytosis
IgG transfer
• Very large
• No concentration gradient (similar levels)
• Picked up by receptors at placental barrier
• Important for protection of fetus from various infections
• But IgG transfer can also work against us…
Viruses
• Likely that some virus transfer to fetus is via endocytosis
How many cell layers are between maternal and fetal blood in 3rd trimester?
2 Layers:
• Fetal capillary Endothelium
• Syncytiotrophoblast
(remember it was 3 layers in first trimester)
What is “Leakage?”
considered a common, but “pathological” form of transfer
Some “micro-tears” can occur in the fragile feto-maternal barrier during 3rd trimester
As a result, some fetal blood can get in to the maternal system and this is how women get exposed to Rh+ blood.
Significant disruption or transfer can occur with “abruptio placenta” and result in a massive fetomaternal hemorrhage and fetal anemia or death.
Ketones?
FFA?
►Ketones
• Used by the fetus as energy when low glucose supply
• Liposoluble so can cross by simple diffusion
►FFA
• Also used by the fetus for energy when low glucose supply (starvation)
• Some too large to cross
• Essential FFA will cross slowly by simple diffusion
• Possibly also some endocytosis
►Transfer will depend on:
• Gradient
• Liposolubility
• Size
Drug transfer across the feto-maternal barrier is based on …
- Molecular size
- Charge
- Gradient
- Degree of drug protein binding (only free drug will cross)
- Liposolubility
How do we anesthetize fetus?
By anesthetizing mom!
Inhalational anaesthetics are liposoluble drugs and will rapidly cross the placenta
Most drugs cross by simple diffusion.
HOWEVER, some are too big to ever cross.
Examples?
Large drug molecules will not cross
• Heparin
• Thyroxin replacement (T4)
• Insulin
The placenta has a profound endocrine function.
Let this blow me away …
Placenta (syncytiotrophoblasts) produces MORE steroid and protein hormones than any other endocrine tissue known in all mammalian physiology and pathophysiology
hCG
►Glycoprotein very similar to LH
– Same α-subunit as LH, FSH, TSH
– Β-subunit unique but similar to LH
►Produced almost exclusively by syncytiotrophoblasts
– This is what makes it such a great pregnancy test
►Detectable in blood
– 8-9 days post-ovulation (~blastocyst implantation)
When is hCG detectable on a home pregnancy test?
Detectable in urine usually a few days before missed period
The vast amount of pregnancies will be detected by this method.
If someone has a positive urine test we really do not need to confirm it by blood
How does hCG change over time?
Serum hCG level doubles every 48 hours, peaks at 10 weeks, then declines and plateaus
hCG
What is its action?
- Purpose of hCG is to rescue & maintain corpus luteum so that progesterone can be made until placenta cant take over progesterone production
- At 6 weeks the placenta will take over progesterone production
- Stimulates fetal testis production of testosterone
hPL
human placental lactogen
►Produced by syncytiotrophoblasts
– not used in preg test as other tissues can produce it)
►Production is proportional to placental mass
– rises steadily until 34-36 weeks
– the bigger the palcenta, the more hPL
– related to Gest DM
hPL
What is its action?
►Nutritional needs of fetus
–“fail-safe” mechanism to ensure adequate nutrient supply to fetus especially in fasting state
►Maternal fasting state
– Lipolysis → increased FFA (source of maternal energy) and ketones (source of fetal nutrition)
►Maternal fed state
– Anti-insulin action: increase in FFA interferes with insulin directed entry of glucose into the cells → higher circulating glucose → favors glucose transport to fetus
Who might have more hPL?
Moms with Twins!
2 placentas!
The amount of placenta dictates the amount of hPL
The more placenta you have, then more hPL!
What is the “keep you pregnant hormone?”
Progesterone!
Pro-gestation
Progesterone
(Precursor: Maternal CHOL)
Where is it produced?
►Production
– Initially by corpus luteum
– hCG rescue of corpus luteum ensures progesterone production by corpus luteum until 6-10 weeks
– Placental production of progesterone takes over at 6-10 weeks
– Also some production by decidua and fetal membranes
Progesterone
(Precursor: Maternal cholesterol)
What is its action?
►Action
– Role in endometrial preparation and implantation
– Maintains uterine quiescence during pregnancy “pro-gestation”
– Smooth muscle relaxation (uterus)
– Inhibits uterine PG production (delays cervical ripening)
– Immunological modulation
– Placental progesterone is a pool of substrate for production of fetal adrenal corticosteroids
What hormone gives women their “healthy glow?”
Where is it produced?
What is it derived from?
Estrogen
Produced: by placenta
Precursor:
– maternal androgens (in early preg)
– fetal androgens (later preg)
Estrogen
– Increased uterine blood flow and CO
– Peripheral vasodilation
– Regulates blood volume by stimulation of RAAS
– Preps uterus for labour
– Involved in uterine contractions in labour
– Prepares breast for lactation
– Increased liver production of hormone-binding globulins
Corticosteroids
►Produced by fetal adrenals
►Precursor: Placental progesterone
►Action
– Promotes fetal lung maturation
– Maternal fluid expansion (to fill the estrogen-vasodilated vessels)
We are skipping the amnion & chorion
It is really challenging and we do not know too much about it
Amniotic Fluid is vital fetal survival
- Cushions the fetus from trauma
- Prevents compression of the umbilical cord
- Allows room for the fetus to grow and move
- Important for limb development
- Critical for LUNG development
- Bacteriostatic properties prevent intra-amniotic infection (fetus is totally sterile)
- Temperature homeostasis
Amniotic Fluid
►First Trimester
- Isotonic with maternal blood
- Likely derived from transudate of maternal and fetal plasma
►Transmembranous
– exchange between maternal compartment (maternal blood in decidua or myometrium) and fetal compartment (AF)
►Intramembranous
– exchange from one fetal compartment to another
– across unkeratinized fetal skin to AF
– across fetal surface of placenta to AF
• Small volume (~50mL by 12 weeks)
