Pregnancy PDF 2024-2025

Pregnancy By Dr.Bushra M.Jarallah Obstetrician/Gynecologist Teacher in the medical school University of Garmian 2024-2025 Embryonic Implantation, Decidua &Placenta The zygote produced by fertilization undergoes mitotic cleavages as it is moved.toward the uterus, forming blastome...

Pregnancy By Dr.Bushra M.Jarallah Obstetrician/Gynecologist Teacher in the medical school University of Garmian 2024-2025 Embryonic Implantation, Decidua &Placenta The zygote produced by fertilization undergoes mitotic cleavages as it is moved.toward the uterus, forming blastomeres which will form the morula No growth occurs during the period of cell cleavage, with blastomeres becoming smaller at each division, and the morula is about the same size as the oocyte at.fertilization About 5 days after fertilization the embryo reaches the uterine cavity, by which time blastomeres have moved to form a central cavity in the morula and the embryo enters the blastocyst stage of development. The blastomeres then arrange themselves as a peripheral layer called the trophoblast around the cavity, while a few cells just inside this layer make up the embryoblast or inner cell mass. The blastocyst remains in the lumen of the uterus for about 2 days,.immersed in the endometrial glands’ secretion on the mucosa byzongisreachthe endurketrion  zygote 217 stesotrophoblast longe yst Implantation, or nidation, involves attachment of the blastocyst to the surface epithelial cells of the endometrium and its proteolytic penetration through this.epithelium into the underlying stroma , a process that lasts about 3 days Cells of the trophoblast drive the events of implantation, during which time cells of the embryoblast rearrange around two new cavities, the amnion and the yolk.sac Where the cells lining these cavities make contact, the bilaminar embryonic disc develops with its epiblast layer continuous with the amnion and its hypoblast. layer continuousx with the yolk sac c All parts of the embryo develop from this early embryonic disc. The yolk sac and amnion form extraembryonic structures, but only the latter persists throughout.pregnancy  spiralartery monochorial onlyonevessel wall inembigo e  endometen ftp.enembrgoisnotrejeetd becauseof :The trophoblast differentiates during implantation into the following The cytotrophoblast, a layer of mitotically active cells immediately around the amnion and yolk sac, and The syncytiotrophoblast, a more superficial, nonmitotic mass of multinucleated.cytoplasm which invades the surrounding stroma By about the ninth day after ovulation, the embryo is totally implanted in the.endometrium and derives nutrients primarily from blood there Cytotrophoblast cells synthesize anti-inflammatory cytokines to prevent an adverse uterine reaction to the implanted embryo and these are supplemented later by various embryonic factors that produce local immune tolerance for the.embryo throughout the pregnancy The endometrial stroma undergoes histologic changes in the period following.implantation Fibroblasts become enlarged, polygonal, more active in protein synthesis, and are now called decidual cells. The whole endometrium is now called the decidua and : includes three areas The decidua is a specialized term used to describe the endometrial lining of the uterus during pregnancy. Bpc The decidua basalis between the implanted embryo and the myometrium; The decidua capsularis, the region between the embryo and the uterine lumen which thins as the embryo gets larger; and The decidua parietalis, on the side of the uterus away from the embryo. to IMP Placenta by theend offirsttrimesteriscomplete The placenta is the site of exchange for nutrients, wastes, O2, and CO2 between the mother and :the fetus and contains tissues from both individuals. It consist of two parts. The chorion(embryonic), derived from the trophoblast Corionfromoftrophoblast Q The decidua basalis(maternal ) On the maternal side blood vessels are eroded, resulting in an open circulation of maternal blood within the vascular space of the placenta. The placental villi are in direct contact with maternal.blood with no intervening layer of maternal endothelial cells(haemomonochorial) Exchange occurs between embryonic blood in chorionic villi outside the embryo and maternal.blood in lacunae of the decidua basalis By the end of the first month of the pregnancy, the placenta contains thousands of tertiary chorionic villi, each branching many times and each branch having one or more capillary loops ,. they provide an enormous surface area for metabolite exchange Exchange of gases, nutrients, and wastes occurs between fetal blood in the capillaries and maternal blood bathing the villi, with diffusion occurring across the trophoblast layer and the.capillary endothelium P The placenta is also an endocrine organ, producing HCG, a lactogen, relaxin, and various growth.factors, in addition to estrogen and progesterone trophoblast  Sy Macroscopic features of the term placenta Measures The term placenta shows a round disc-like appearance, with the insertion of the umbilical cord in a slightly.eccentric position on the fetal side of the placenta The average measurements of a delivered placenta at :term are as follows diameter 22 cm, central thickness 2.5 cm, and weight 450–500 g. One has to keep in mind, though, that considerable variation in gross placental structure can occur in normal term pregnancies. In part, this is due to the fact that the human placenta comprises 30–50 operational units termed placentomes, whose aggregated shape may vary without compromise to the.function of individual units Gign.aisoand'splacenta jWhas no Tissue arrangements :In term placenta On the fetal side of the placenta, the amnion covers the.chorionic plate The amnion is assembled by a single-layered cuboidal epithelium fixed to an avascular layer of mesenchymal.tissue Beneath the amnion, the chorionic mesenchymal tissue layer contains the chorionic plate vessels that are direct.continuations of those within the umbilical cord Hence, the chorionic vessels connect the fetal circulation (via the umbilical cord) with the placental circulation within.the villous trees of the placenta The villous trees hang down from the chorionic plate, floating within a vascular space filled with maternal blood. The villous trees are connected via a major trunk (stem villus) to the chorionic plate and display multiple sites of.branching, finally ending in terminal villi artificial a's natural d placenta jwa.ba On the maternal side of the placenta, the. basal plate is located It is an artificial surface generated by separation of the placenta from the uterine wall during delivery. The basal plate is a colourful mixture of fetal trophoblasts and maternal cells of the decidua, all of which are embedded in trophoblast-secreted matrix-type fibrinoid, decidual extracellular matrices,.and blood-derived fibrin-type fibrinoid At the placental margin, chorionic plate and basal plate fuse with each other, thereby closing the intervillous space such that the remainder of the uterine cavity is lined by the fetal membranes or chorion.laeve Placental development Trophoblast lineage At the transition between morula and blastocyst, the trophoblast lineage is the first to differentiate from the inner cell mass or embryoblast attachment of the blastocyst to the endometrial epithelium, further differentiation of the trophoblast occurs. At this stage the first event is the creation of an outer layer of fused trophoblast cells, termed the outer syncytiotrophoblast. This outer layer generated by fused trophoblasts is in direct contact with maternal tissues and thus is the first layer from the conceptus to encounter and subsequently penetrate the uterine epithelium capillaries The development of the lacunar system subdivides the placenta into its three.compartments The embryonically oriented part of the trophoblast together with the (1.extraembryonic mesoderm (chorion) will develop into the chorionic plate The trabeculae will become the anchoring villi, attaching the placenta proper (2 to the uterine wall. The side branches growing out of the trabeculae will develop into floating villi. The lacunae surrounding the villi will turn into the intervillous space that will subsequently fill with maternal blood at the end of the first.trimester The maternally oriented part of the trophoblast together with components of (3.maternal decidual tissues will develop into the basal plate Early villous stage Starting at day 12 post conception, proliferation of cytotrophoblast pushes trophoblasts to penetrate the syncytial trabeculae, reaching the maternal side of the syncytiotrophoblast.by day 14 primary villi (day 14) secondary villi( after day 14) tertiary villi(day 20-21) Placental villi are organized in villous trees that cluster together.into a series of spherical units known as lobules or placentomes All these cells migrate as interstitial trophoblast into the decidual stroma. The interstitial trophoblast invades the whole thickness of.the decidua and penetrates the inner third of the myometrium Here, invasion normally stops and no extravillous trophoblast can.be seen in the outer third of the myometrium exchangofthe material betweenmomandfetusisgradually 3 thesecanmore to liable Plugging of spiral arteries totipotent at cancerif rapiddivision Invasion of extravillous trophoblasts is the ultimate means to transform maternal arteries into large-bore conduits to enable adequate supply of oxygen and nutrients to. the placenta and the fetus However, free transfer of maternal blood to the intervillous space is only established at the end of the first trimester of pregnancy. Before that, the extent of invasion and thus the number of endovascular trophoblasts is so great that the trophoblasts aggregate within the arterial lumen, plugging the distal segments of the spiral arteries. Hence, before about 12 weeks of gestation, the intervillous space contains mostly a plasma filtrate that is free of maternal blood cells. To aid in nutritional support of the embryo, glandular secretion products from eroded uterine glands (histiotrophic nutrition) add to. the fluids filling the intervillous space The reason for such paradoxical plugging of already eroded and transformed arteries may be because the lack of blood cells keeps the placenta and the embryo in a low oxygen environment of less than 20mmHg in the first trimester of pregnancy. This low oxygen environment may be necessary to drive angiogenesis and at the same time reduce formation of free radicals that could damage the growing embryo in this critical. stage of tissue and organ development Onset of maternal blood flow At the end of the first trimester trophoblastic plugs within the spiral arteries break up to allow maternal blood cells to enter the intervillous space, thereby establishing the first arterial blood flow to the placenta (haemotrophic nutrition). The inflow starts in those upper parts of the placenta that are closer to the endometrial epithelium (the abembryonic pole of the placenta). These sites are characterized by a slight delay in development since the deeper parts at the embryonic pole have been the first to develop directly after implantation. Therefore, at these upper sites the plugs inside the vessels contain fewer cells, enabling blood cells to penetrate the plugs earlier, and blood flow starts at these sites first, maybe even weeks prior to the embryonic pole. Because of the massive increase in oxygenation at this time (around weeks 8–10) at the abembryonic pole, placental villi degenerate in larger parts and the chorion becomes secondarily smooth. The regression leads to the formation of the fetal membrane or chorion leave. The remaining part of the placenta develops into the chorion.frondosum , the definitive disc-shaped placenta Basic structure of villi Villous trophoblast The branches of the syncytial trabeculae are the forerunners of the placental villi. Throughout gestation the syncytial cover remains and forms the placental barrier between maternal blood in the intervillous space and the fetal vessels within the.mesenchymal core of the villi Villous cytotrophoblast The layer of mononucleated villous cytotrophoblast cells is the basal layer of the villous trophoblast compartment resting on the basement membrane underneath the multinucleated layer of syncytiotrophoblast. Villous cytotrophoblasts are a heterogeneous population: a subset proliferates throughout gestation ,some exhibit a progenitor status because they can be induced to differentiate along the extravillous pathway, while others are in. varying stages of differentiation  Willieincreasesurfacearea The number of villous cytotrophoblasts continuously increases during pregnancy, from about 1 ×. 109 at 13–16 weeks to about 6 × 109 at 37–41 weeks of gestation Villous cytotrophoblasts do not normally come into direct contact with maternal blood, unless. focal damage occurs to the overlying syncytiotrophoblast If focal areas of syncytiotrophoblast are lost, for example due to focal necrosis, the deficit is filled with fibrin-type fibrinoid (a maternal blood clot product) that covers the exposed. cytotrophoblasts Villous syncytiotrophoblast The syncytiotrophoblast is a multinucleated layer without lateral cell borders, hence there is a. single syncytiotrophoblast covering all villi of a single placenta Microvilli on its apical surface provide amplification of the surface (sevenfold) and are in direct contact with maternal blood floating within the intervillous space. Growth and maintenance of the syncytiotrophoblast is dependent on fusion with the underlying cytotrophoblasts, since syncytial nuclei do not divide and thus the syncytiotrophoblast 5.does not proliferate  syncytial fusion remains critical for maintaining the functional and structural integrity of the syncytiotrophoblast, for example secretion of hormones such as chorionic gonadotrophin and the surface expression of energy-dependent transporters for the uptake of molecules such as glucose or amino acids. Consequently, nuclei that are incorporated into the syncytiotrophoblast remain within this layer for about 3–4 weeks. Then, the older nuclei accumulate and are packed into protrusions of the apical membrane known as syncytial knots. Villous trophoblast turnover Like every epithelium, the villous trophoblast exhibits the phenomenon of : continuous turnover, comprising the following steps ;proliferation of a subset of cytotrophoblast progenitor cells (1 differentiation of post-proliferative mononucleated daughter (2 ;cytotrophoblasts (2–3 days) syncytial fusion of finally differentiated cytotrophoblasts with the overlying (3 ;syncytiotrophoblast further differentiation and maturation of cellular components and organelles (4 ;within the syncytiotrophoblast (3–4 weeks) ;ageing and late apoptosis at specific sites of the syncytiotrophoblast (5 packing of older material into syncytial knots; and finally (6 syncytial knots and smaller micro-particle fractions may be extruded or (7. secreted into the maternal circulation In pathological pregnancies the molecular control of trophoblast differentiation may be altered. In cases of severe early-onset fetal growth restriction (FGR) this physiology is likely disturbed in favour of greater apoptotic shedding, while in cases of pre-eclampsia this physiology is disturbed in favour of both greater apoptotic shedding combined with the release of necrotic and aponecrotic. material into the maternal circulation Villous stroma The stromal villous core comprises a population of fixed and moving connective : tissue cells, including mesenchymal cells and fibroblasts in different stages of differentiation up to ;myofibroblasts placental macrophages (Hofbauer cells); and placental vessels with smooth muscle cells and endothelial cells Fetal membranes During early embryonic development, the amnionic cavity increases in size. and finally surrounds and encases the complete embryo o Fluid accumulation within the amnionic cavity leads to complete separation of the embryo from surrounding extraembryonic tissues, leaving only the developing umbilical cord as the connection between.placenta and embryo sad Layers of the chorion laeve The layers of the chorion laeve, from the fetal to the maternal side, are as follows : outside inside Amnionic epithelium. A single cuboidal epithelium that secretes and resorbs (1 6 the amnionic fluid and is involved in removal of carbon dioxide and pH regulation.of the amnionic fluid Amnionic mesoderm. A thin layer of avascular connective tissue separated (2.from the amnionic epithelium by a basement membrane Chorionic mesoderm. This second layer of connective tissue is separated from (3 c the amnionic mesoderm by slender fluid-filled clefts. It is continuous with the connective tissue of the chorionic plate, which contains the branching vessels to.and from the umbilical and villous vessels Extravillous trophoblast of the fetal membranes. This specific type of (4 extravillous trophoblast does not display invasive properties and is separated.from the chorionic mesoderm by a basement membrane Capsular decidua. This layer of maternal cells is directly attached to the (5 extravillous trophoblast. At the end of the implantation process, the decidua Ii closes again over the abembryonic pole of the developing embryo, generating the capsular decidua. During the early second trimester, the capsular decidua comes into direct contact with the opposite wall of the uterus, causing.obliteration of the uterine cavity EE d down i fetus 5204 seds vessel 2 Jul core Eg Ultrasound Transvaginal ultrasound can detect the gestational sac at the 5–6 week..postmenstrual stage of pregnancy In the second trimester, the organization of the placenta and umbilical cord,. together with its maternal blood supply, can be readily defined Minor anatomical variations, such as cysts and lakes, can readily be distinguished from lesions that destroy functioning villous tissue, such as infarcts and.intervillous thrombi Small placentas typically have eccentric cords, due to chorionic regression, and. are a risk factor for early-onset FGR It is important to document placental location (for placenta praevia) and cord.insertion (for vasa praevia) for ongoing management Pathological placental invasion (placenta percreta), typically in association with placenta praevia and previous caesarean deliveries, may be suspected by. ultrasound , and can be confirmed by magnetic resonance imaging (MRI) sometimes uteruspenetrate Dangerons because Labor ithasaseverbleeding Blad couse bl e ng isinfront ofuterus and Uterus pull it andmay casepenetratingit Ultrasound (including Doppler and colour power Doppler ultrasound).Week o 4: visualization of the gestational sac.Week 7–8: visualization of blood flow in the umbilical cord c Week 13 until delivery: visualization of placental O.vessels with a diameter larger than 200 μm.Week 14: establishment of EDF in the umbilical arteries -Week 18–22: screening ofFiastolicuterineflow arteries for patho.logical flow patterns fetalgrowthrestriction Week 22: early-onset FGR can be predicted by absent.EDF in the umbilical arteries Maternal Physiology The physiological changes of pregnancy are strongly proactive, not reactive, with the luteal phase of every ovulatory menstrual cycle ‘rehearsing’ for pregnancy. Most pregnancy-driven changes are qualitatively in place by the end of the first trimester, only maturing in magnitude thereafter. Immunology Only two types of fetal tissue come into direct contact with maternal tissues: the villous trophoblast and the extravillous trophoblast. Villous trophoblast, which is a continuous syncytium, is bathed in maternal blood but seems to be. immunologically inert Both recurrent miscarriage and pre-eclampsia are associated with poor trophoblast invasion. \NK cells appear and disappear in the endometrial decidua every ovulatory menstrual cycle, and the populations are maintained should conception occur. When progesterone is at its peak, they associate with the spiral arteries and uterine glands. This has ceased by 12–14 weeks. It has been suggested that NK cells are essential for spiral artery remodeling. The uterus.Nutrition of the fetus is from the uterus in early pregnancy The inner third of the myometrium and the endometrium, is anatomically __.changed by pregnancy, these changes appear to be irreversible The spiral arteries become floppy thin-walled vessels, resembling veins than arteries, allowing the maximum flow to reach the placenta. This remodelling is only completed in the early second trimester, but is impaired.in both pre-eclampsia and normotensive intrauterine growth restriction The uterus must be quiescence until labour is initiated , progesterone and locally generated nitric oxide, brain natriuretic peptide, prostacyclin,. prostaglandin (PG)E2 and calcitonin gene- related peptide and are relaxatory Cardiovascular system o_0 There is a fall in total peripheral resistance by 6 weeks’ gestation to a nadir of about 40% by mid-gestation, resulting in a fall in afterload. This allows the necessary expansion of. plasma volume (PV) By the late third trimester, the PV has increased by about 50% in a first pregnancy and 60% in a second or subsequent pregnancy. The bigger the expansion, the bigger, on.average, the birthweight of the baby The total extracellular fluid volume rises by about 16% by term, so the percentage rise in PV is disproportionate to the whole. The plasma osmolality falls by about 10 mosmol/kg.as water is retained do a The heart rate rises by 10–15bpm, so the cardiac output begins to rise. There is probably a fall in baroreflex sensitivity as pregnancy progresses, and heart rate variability falls. Stroke volume rises a little later in the first trimester. These two factors push the cardiac output up by 35–40% in a first pregnancy, and by about 50% in later pregnancies; it can. rise by a further third in labour IMP 0 Korotkoff 5 should be used with auscultatory. techniques However measured, there is a small fall in systolic, and a greater fall in diastolic, blood pressure, initiated during the luteal phase, being mainly complete by 6–7 weeks’ gestation, but continuing more slowly to the late second trimester, resulting in.an increased pulse pressure The blood pressure then rises steadily, in parallel with an increase in peripheral sympathetic activity, and even in normotensive women there may be.some late overshoot of non-pregnant values Supine hypotension occurs in about 8% of women in late gestation as the uterus falls back onto the.inferior vena cava, reducing venous return The venous pressure in the lower circulation rises, for both.mechanical and hydrodynamic reasons The pulmonary circulation is able to absorb high rates of flow without an increase in pressure so pressure in the right ventricle, and the pulmonary arteries and capillaries, does not change. Pulmonary resistance falls in early pregnancy, and does not change thereafter. There is progressive venodilatation and rises in venous distensibility and capacitance throughout a normal pregnancy, possibly because of.increased local nitric oxide synthesis :Clinical aspects of CVS changes Breathlessness, edema of extremities, sinus tachycardia (palpitation), filled and dynamically pulsating jugular veins, but JVP unchanged, forcibly beating cardiac ,apex :Auscultatory changes.increase loudness of S1, S2(1.exaggerated splitting of S2(2 D.loud S3 by 20 weeks(3.systolic ejection murmur at left sternal edge (96%)(5 o.transient diastolic murmur (20%)(6.continuous murmur due to increase mammary blood flow(10%)(7 ?What are the ECG changes in normal pregnancy The respiratory system Diaphragm is displaced o. A-P and transverse diameters of the thorax increase o Tidal volume rises by about 30% in early pregnancy to 40–50% above non-pregnant o. values by term, with a fall in expiratory reserve and residual volume Neither forced expiratory volume in 1s (FEV1) nor peak expiratory flow rate are affected by pregnancy, even in women with asthma. The rise in tidal volume is largely driven by progesterone, which appears to decrease the threshold and increase the sensitivity of.the medulla oblongata to carbon dioxide Respiratory rate does not change. This over-breathing begins in every luteal phase; the.Pco2 is lowest in early gestation There is an increase of about 16% in oxygen consumption by term due to increasing maternal and fetal demands , so there is physiological hyperventilation. 3 meet v1  physiological anemia Hematology The circulating red cell mass rises by 20–30% during pregnancy, with increases in both cell _F number and size. It rises more in women with multiple pregnancies, and substantially more.with iron supplementation (~29% compared with 17%) Serum iron concentration falls, the absorption of iron from the gut rises and iron-binding capacity rises in a normal pregnancy, since there is increased synthesis of the β1-globulin.transferrin.Nevertheless, 75% of diagnosed anaemia in pregnancy arises from iron deficiency Plasma folate concentration halves by term, because of greater renal clearance, although red.cell folate concentrations fall less o Pregnant adolescents seem to be at particular risk of iron deficiency. Even relatively mild maternal anaemia is associated with increased placental weight/birthweight ratios and decreased birthweight. However, inappropriate supplementation can itself be associated with pregnancy problems. The National Institute for Health and Care Excellence (NICE) recommends that iron supplementation should be considered for women with haemoglobin concentrations B ee. below 110 g/L in the first trimester and 105 g/L at 28 weeks Erythropoietin rises in pregnancy, more so if iron supplementation is not taken (55% compared with 25%) but the changes in red cell mass antedate this; human placental lactogen.may stimulate haematopoiesis  plasmavolume P Hematocrit The PV increases more than the red cell mass leads to a fall in the.haematocrit, haemoglobin concentration and red cell count The fall in packed cell volume from about 36% in early pregnancy to about 32%.in the third trimester is a sign of normal PV expansion The total white cell count rises, mainly because of increased polymorphonuclear leucocytes. Neutrophil numbers rise with oestrogen concentrations and peak at about 33 weeks, stabilizing after that until labour and the early puerperium, when they rise sharply. Their phagocytic function increases during gestation. T and B lymphocyte counts do not change but their function is suppressed, making pregnant women more susceptible to viral..infections, malaria and leprosy Platelet count and platelet volume are largely unchanged in most pregnant women, although their survival is reduced. Platelet reactivity is increased in the second and third trimesters and does not return to normal until about 12.weeks after delivery increasein Coagulationfactor'd gas Bleeding JE topenetration d Coagulation The changes in coagulation profile during pregnancy are most complex at the time of labour and delivery, with the urgent need to prevent life-threatening haemorrhage from the placental separation site, while avoiding excessive.activation and thrombosis Continuing low-grade coagulopathy is a feature of normal pregnancy. Several of the potent procoagulatory factors rise from at least the end of the first trimester. For example, factors VII, VIII and X all rise, and absolute plasma fibrinogen i 0.doubles, while antithrombin III, an inhibitor of coagulation, falls The erythrocyte sedimentation rate rises early in pregnancy due to the increase in.fibrinogen and other physiological changes Protein C, which inactivates factors V and VIII, is probably unchanged in O pregnancy, but concentrations of protein S, one of its cofactors, fall during the.first two trimesters An estimated 5–10% of total circulating fibrinogen is consumed during placental. separation o Plasma fibrinolytic activity is decreased during pregnancy and labour, but returns. to non-pregnant values within an hour of delivery of the placenta out 2BCmass Hematocrit 13 Folate b uncharge P It wbc During pregnancy, signi cant hematological changes occur to support the growing fetus and prepare the mother for childbirth. These changes involve blood volume, red and white blood cells, coagulation factors, and iron metabolism. Below is an overview: 1. Blood Volume Plasma Volume: Increases by 30–50% by the third trimester. This helps meet the increased oxygen and nutrient demands of the fetus and placenta. Red Blood Cell (RBC) Mass: Increases by about 20–30%, but the rise is less than plasma volume, leading to physiological anemia of pregnancy due to hemodilution. 2. Hemoglobin and Hematocrit Hemoglobin (Hb): Decreases slightly due to dilution, but levels below 11 g/dL suggest true anemia. Hematocrit: Decreases because of the plasma volume increase. 3. White Blood Cells (WBCs) Leukocytosis: WBC count increases, especially during labor, as a physiological response. WBC counts can rise from a normal baseline of 6,000–16,000/mm³ to 20,000–30,000/mm³ during labor. 4. Platelets Mild Thrombocytopenia: Platelet count may decrease slightly in late pregnancy, often within the normal range (≥150,000/mm³). However, counts