Session 8 Flashcards
When and how does implantation occur? What does it achieve?
Implantation begins at day 6 of the pregnancy, where the trophoblast (syncytiotrophoblast) cells interact with the endometrial lining of the uterus once it has ‘hatched’ and lost the zona pellucida.
The blastocyst then becomes embedded within the endometrium, to interact with the increased vasculature and secretory glands of the endometrium that have developed during the menstrual cycle.
- Implantation is interstitial – the uterine epithelium is breached and the conceptus implants within the stroma
- The placental membrane becomes progressively thinner as the needs of the fetus increase - More efficient exchange across membrane
- One layer of trophoblast will ultimately separate maternal blood from fetal capillary wall – But the two circulations never mix
Achievements of implantation:
- It establishes the basic unit of exchange:
Primary villi - early finger like projections of trophoblast
Secondary villi - invasion of mesenchyme into core
Tertiary villi - invasion of mesenchyme core by fetal vessels
- Anchors the placenta
- Establishes maternal blood flow within the placenta
Where does implantation normally occur and what happens when this goes wrong?
Implantation typically occurs within the superior body of the uterus. Implantation can occur in the wrong place, either outside of the endometrium, or at a site within the lower uterine segment. Implantation can also occur at the site of previous C-section scars, which are not typically viable.
These conditions may require emergency assessment.
Invasion that is too deep is known as placenta accreta, and incomplete invasion of the conceptus can also lead to complications such as miscarriage or placental insufficiency.
• I Implantation in the wrong place
– Ectopic pregnancy - implantation at site other than uterine body (most commonly Fallopian tube). Can be peritoneal or ovarian. Can very quickly become lifethreatening emergency
– Placenta praevia -implantation in the lower uterine segment can cause haemorrhage in pregnancy can require C-section delivery
• II Incomplete invasion
– placental insufficiency
– pre-eclampsia
Describe the development of the placenta
The placenta begins to develop in the second week of the pregnancy. It is the very first structure that begins to develop, prior to any embryological development. There cannot be a healthy pregnancy without a healthy placenta.
The placenta is a specialisation of an area of ‘fetal membranes’ surrounding the fetus. The placenta develops from trophoblast cells (outer cell mass) to support the pregnancy.
At week 2 we have two distinct layers formed from our outer cell mass - the syncytiotrophoblast (outer), and the cytotrophoblast (inner). these two laters constitute the chorion. The inner cell mass becomes the bilaminar disk (epiblast (goes onto become the embryo) and hypoblast)
Initially, following implantation, the amniotic membrane is separate to the chorionic membrane. As the amniotic sac enlarges, the chorionic sac is displaced, and the amniotic membrane fuses with the chorionic membrane to produce a single amniotic cavity.
Syncytiotrophoblast cells make human chorionic gonadotrophin which is required to maintain the corpus luteum.
Projections around the outer surface of the membrane are initially balanced over the entire surface, however as this growth occurs, the projections are concentrated into a single disc-like space, which goes on to become the placenta.
What are chorionic villi?
Implantation achieves the initial unit of exchange, known as villi, from the conceptus. These villi, or projections, come from the trophoblast cells. They branch out as a tree-like structure, with an outer layer of syncytiotrophoblast and the core is comprised of connective tissue where fetal blood vessels can develop.
Maternal blood vessels then surround these villi, allowing exchange to occur. The barrier between maternal and fetal blood flow is a single layer of trophoblast for optimal transport, but the two circulations never mix. In the first trimester, this barrier between fetal and maternal blood is relatively thick with a full layer of cytotrophoblast and syncytiotrophoblast. As the pregnancy progresses, this barrier becomes progressively less by reducing the number of cytotrophoblast cells to be more optimised for transport.
- The placenta is a specialisation of the chorionic membrane
- Chorion frondosum - the part of the chorion that has persistent villi and that with the decidua basalis forms the placenta
Structure:
First trimester villus - thick barrier
Third trimester - barrier at optimal thinness. Some cells are kept to act as stem cells for repair. Two factors cause the thinning - loss of cytotrophoblast layer and margination of foetal capillaries so capillaries are pushed right against wall of villus.
What is decidua?
This term relates to the cells of the endometrium that become specialized to modulate the degree of invasion of the conceptus once it has implanted. This occurs through a decidual reaction (‘decidualisation’), and is balanced by factors that promote and inhibit decidualisation.
This is important because if the conceptus implants in a location where there is no decidua (e.g. tubal ectopic pregnancy), there is no inhibition of decidualisation and therefore no control over the extent of invasion. If implantation occurs in the correct place but the decidual reaction is suboptimal, it can lead to a range of complications where the pregnancy is either not maintained (which can lead to miscarriage or infertility), or a spectrum of placental insufficiency including pre-eclampsia
Describe how maternal and foetal blood vessels interact
The maternal blood vessels are called the endometrial arteries and veins, which essentially bathe the outside of the villi in maternal blood for exchange to occur. The foetal blood vessels bring waste products to the villi through the umbilical arteries (paired), and takes oxygen and nutrients to the foetus via the umbilical vein (singular).
Umbilical arteries and vein run through umbilical cord.
- Two umbilical arteries – Deoxygenated blood from fetus to placenta
- One umbilical vein – Oxygenated blood from placenta to fetus
What is the endocrine function of the placenta?
The placenta produces protein hormones, such as human chorionic gonadotrophin (hCG). This hormone is produced by the syncytiotrophoblast, and is therefore pregnancy specific and can be analysed in urinary and serum pregnancy testing. This hormone sustains the corpus luteum in the first trimester.
Human Chorionic Gonadotrophin (hCG)
- produced during the first 2 months of pregnancy
- supports the secretory function of corpus luteum
- produced by syncytiotrophoblast therefore is pregnancy specific
- excreted in maternal urine therefore used as the basis for pregnancy testing
- also marker for trophoblast disease – molar pregnancy (hydatidiform mole) – choriocarcinoma
Placental steroid hormones
- progesterone and oestrogen • responsible for maintaining the pregnant state
- placental production takes over from corpus luteum by the 11th week
Protein hormones produced by placenta: human chorionic gonadotrophin (hCG), human chorionic somatomammotrophin (hCS), human chorionic thyrotrophin, human chorionic corticotrophin
Placental hormones influence maternal metabolism
- Progesterone – increased appetite - lay down fat stores in early pregnacy to be used in later trimesters
- hCS / hPL – creates insulin resistance state in mother so more glucose available for foetus
Describe the function of the metabolic changes of the placenta
Placental hormones then have an impact on maternal metabolism. Progesterone promotes an increase in appetite to allow an increased fat deposition to help support the fetus and breastfeeding later on in the pregnancy. Other hormones such as human placental lactogen (hPL) creates a diabetogenic state to cause insulin resistance in the mother, increasing the glucose availability to the fetus.
How does transport occur at the placenta?
- Simple diffusion – molecules moving down a concentration gradient • water • electrolytes • urea and uric acid • gases
- Facilitated diffusion – applies to glucose transport
- Active transport • specific “transporters” expressed by the syncytiotrophoblast – amino acids – iron – vitamins
Pathophysiology of placental transport
- the placenta is not a true “barrier”
- teratogens can access the fetus via the placenta
- unintentional outcomes from physiological process – Haemolytic disease of the newborn secondary to Rhesus incompatibility of mother and fetus
Describe how gas exchange happens at the placenta?
Follows simple diffusion. Rate of exchange in gas exchange is flow limited, not diffusion limited. Fetal O2 stores are small therefore adequate uteroplacental circulation is required, and if compromised e.g. during labour, contraction can lead to compression of the blood vessels and ‘fetal distress’.
Describe the transfer of immunity to the foetus. When are teratogens most dangerous?
The immune system of the fetus is very immature. However, antibodies can be transported across the placenta into the fetal circulation so that at the time of birth the fetus has some defence against infection. Only certain types of imunoglobilins can cross the placenta, specifically IgG. IgG concentrations in fetal plasma exceed those in maternal circulation. Transfer is a receptor-mediated process, maturing as pregnancy progresses
Teratogens have their greatest effect in early pregnancy, particularly in the embryonic stage (3-8 weeks) as this is a key time for development of the body systems. In the fetal period (9-36 weeks), most of those systems have developed and only need to grow, so the effects tend to be less severe (other than the central nervous system). CNS still at risk as is last to finish development.
Pregnancy is considered to be an immunecompromised state for the mother, and therefore infections that may not have had serious consequences in an adult can have more significant consequences in pregnancy.
What kind of harmful substances can be transported to the foetus?
Transfer across the placenta can also lead to harmful substances (‘teratogens’) being transferred as well.
Blood group incompatibilities can also occur, such as Rhesus disease of the new-born, where maternal antigens can cross into the fetal circulation and attack fetal blood cells
Other teratogens that can ass through the placenta to the foetus.
- thalidomide – Limb defects
- Alcohol – fetal alcohol syndrome and Alcohol-related neurodevelopmental disorder
- therapeutic drugs – Anti-epileptic drugs – Warfarin – ACE inhibitors
- drugs of abuse – Dependency in the fetus and newborn
- maternal smoking
Describe glucose metabolism in preganncy. What happens when mother is already insulin resistant?
Glucose and amino acid metabolism are altered in pregnancy to favour nutritional supply to the fetus. The fat which is laid down in the first half of pregnancy in the mother helps meet the demands of the fetus later in the pregnancy when the fetus is metabolically most demanding.
The changes which occur include:
Reduction in maternal blood glucose and amino acid concentrations
Diminished maternal responsiveness to insulin (insulin resistance) in the second half of pregnancy
Increase in maternal free fatty acid, ketone and triglyceride levels (as an alternative metabolic fuel)
increased insulin release in response to a normal meal
These changes are achieved through the combined actions of:
- Human Placental Lactogen (hPL) hPL and ‘human chorionic somatomammotrophin’ (hCS) generates a maternal resistance to insulin. Pancreas would normally try to produce more insulin in response to overcome this resistance. The hormone prolactin also has a similar role. In addition hPL also contributes to increased breakdown of lipids to fatty acids.
- Oestrogen - This hormone stimulates an increase in prolactin release. It also causes liver to produce more glucose through gluconeogenesis
- Progesterone - This hormone increases appetite in the first half of pregnancy, and diverts glucose into fat synthesis. Maternal glucose usage thus declines and gluconeogenesis increases, maximizing availability of glucose to the fetus. In later pregnancy, the mother’s energy needs are met by metabolizing peripheral fatty acids
If already in an insulin resistant state e.g. from type 2 diabetes, polycystic ovary or obesity, insulin reistance will further increase putting a higher demand on your pancreas to produce more insulin. If demand too great on pancreas for it to keep up then it can lead to persistant hyperglycaemia. Insulin can’t cross the placenta but the glucose can easily. This results in higher glucose levels in the foetal circulation. Foetus needs to produce its own insulin, insulin is closely related to growth factors, so baby will have increased growth. Leads to gestational diabetes.
What is gestational diabetes?
Gestational Diabetes is defined as glucose intolerance that is first recognised in pregnancy, and does not persist after delivery. It is diagnosed using the oral glucose tolerance test, and is essentially where resistance to insulin is not met with a compensatory rise in maternal insulin, leading to maternal hyperglycaemia. This poses a risk of causing harm to the fetus. It is associated with increased birth weight, congenital defects (e.g brachial plexus injury)and stillbirth. Therefore good antenatal care and monitoring are required. Usually diagnosed in second trimester when hPL iis highest. Increased baby growth from too much glucose called macrosomia which can cause birth problems such as tears so often birth carried out through C-section. Women with gestational diabetes are more at risk of type 2 diabetes later in life.
Describe the haemotological and cardiovascular changes seen in pregnancy
Baby needs increasing delivery of nutrients.
Mother needs to fill utero-placental circulation, oxygenate the growing uterus as its very vascular and has high demand. also needs to be protected from impaired venous return and prepare for potential blood loss during delivery. This is achieved through volume expanion and clotting mechanisms
Increase in volume is seen early whereas increased heart rate is seen later (no more than 95bpm)
As pregnancy advances, the fetal-placental unit’s increasing need for nutrition is met via maternal vascular-neogenesis. This is accommodated by changes in function of the maternal baro- and volume receptors. There is also increased blood flow to the growing breasts, kidneys and GI tract (increased metabolism).
Plasma volume increases by about 50%, (red cell mass by about 20%). Cardiac output increases from 4.5 to 6 L/min. This is achieved mainly through increase in stroke volume as compared to heart rate, but the cardiac output, stroke volume and heart rate all increase.
Drop in BP stimulates RAAS system. additionally oestrogen and progesterone stiumulate extra renin and oestrogen stimulates further production of angiotensinogen. This leads to increased aldosterone so more water and sodium reabsorbed from kidneys. Angiotensinogen 2 doesnt work as well in pregnancy so doesn’t cause vasoconstriction possible due to overwhelming effect of progesterone. This all can cause preripheral oedema.
Venous distension and engorgement can also lead to varicose veins and haemorrhoids
Due to the increase plasma volume, flow murmurs can occur in pregnancy, as well as upward displacement of the apex beat.
Progesterone levels are continually increasing, and will cause vasodilation. This fall in total peripheral resistance (TPR) can cause a drop in mean arterial blood pressure, and can result in hypotension. Normal BP in pregnancy <140/90
Overall, plasma volume increases whilst peripheral vascular resistance often falls during pregnancy. This initially causes lower blood pressure in the first and second trimester, but this usually returns to normal by the third trimester. With the increased blood volume, the red cell mass also increases, but not to the same extent. This can therefore lead to a physiological anaemia called dilutional anaemia. Anaemia can also occur during pregnancy due to iron and folate deficiency. Dilutional anaemia usually not treated (unless Hb under 100) due to higher risk of haemorrhage and intra uterine growth deficiency.
Pregnancy is a pro-thrombotic state due to increased clotting factors - fibrinogen, factor VIII and vWF. Decreased anticoagulants such as protein S, as well as reduced fibrinolysis. This can lead to thromboembolic disease in pregnancy, however this cannot be treated with warfarin as warfarin is teratogenic and can cross the placenta. Venous stasis fro compression of IVC will also contribute to this hypercoagulability.
D-dimers cannot be used to rule out DVT or pulmonary embolism as they’re high during pregnancy anyway so ultrasound used instead.
Describe the importance of the gross morphology of the placenta
Maternal aspect will have cobblestone like appearence with cotyledons that increase surface are but must be checked that none have been lost and left inside the mother as this can cause post partum haemorrhage.
