The placenta and fetal membranes

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1. DR . SNIGDHA KUMARI SENIOR RESIDENT ESIC-PGIMSR, KOLKATA THE PLACENTA AND FETAL MEMBRANES

2. The human placenta is - discoid haemochorial deciduate larynthine The placenta is attached to the uterine wall and establishes connection between the mother and fetus through the umbilical cord.

3. Fetal component– from chorion frondosum Maternal component – from decidua basalis DEVELOPMENT

4. Interstitial implantation completed on 11 th day. The blastocyst is surrounded on all sides by lacunar spaces around cords of syncytial cells , called trabeculae . Implantation of the blastocyst Occurs 6 or 7 days after fertilization

5. On 13 th day - Stem villi developes from trabeculae . - Stem villi connect the chorionic plate with the basal plate. - Primary, secondary and tertiary villi are successively developed from stem villi. On 21 st day - Arterio -capillary-venous system in the mesenchymal core of each villus is completed.

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9. At 3 rd to 4 th week lacunar spaces become confluent and form multilocular receptacle lined by syncytium and filled with maternal blood. This space becomes future intervillous space.

10. DECIDUA This is the endometrium of the gravid (pregnant) uterus. It has four parts: Decidua basalis Decidua capsularis Decidua parietalis Decidua reflexa 13

11. DEVELOPMENT OF PLACENTA Until the beginning of the 8 th week, the entire chorionic sac is covered with villi. After that, as the sac grows, only the part that is associated with Decidua basalis retain its villi. Villi of Decidua capsularis compressed by the developing sac. Thus, two types of chorion are formed: Chorion frondosum (villous chorion) Chorion laeve – bare (smooth) chorion About 18 weeks old, it covers 15-30% of the decidua and weights about 1\ 6 of fetus 14

12. C0nt.. The villous chorion ( increase in number, enlarge and branch ) will form the fetal part of the placenta. The decidua basalis will form the maternal part of the placenta. The placenta will grow rapidly. By the end of the 4 th month, the decidua basalis is almost entirely replaced by the fetal part of the placenta. 15

13. GROWTH OF THE PLACENTA Upto 16 th wk the placenta grows both in thickness and circumference , after that there is little increase in thickness but it increases circumferentially till term.

14. Covered by smooth glistening amnion with the umbilical cord attached at or near centre. At term about four –fifths of the placenta is of fetal origin. FETAL SURFACE

15. Rough and spongy. Maternal blood gives it a dull red colour . It is mapped out into 15 to 20 somewhat convex polygonal areas known as lobes or cotyledons which are limited by fissures. Only the decidua basalis and the blood in the intervillous space are of maternal in origin. MATERNAL SURFACE

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17. The placenta consists of two plates— The chorionic plate lies internally and lined by amniotic membrane. The umbilical cord is attached to this plate. The basal plate lies to the maternal aspect. Between the two plates lies the intervillous space containing the stem villi and their branches , the space being filled with maternal blood.

18. From within outwards it consists of – Primitive mesenchymal tissue containing branches of umbilical vessels A layer of cytotrophoblast and Syncytiotrophoblast . The stem villi arise from the plate. It forms the inner boundary of choriodecidual space. CHORIONIC PLATE

19. It consists of the following structures from outside inwards-- Part of the compact and spongy layer of the decidua basalis Nitabuch’s layer of fibrinoid degeneration of the outer Syncytiotrophoblast at the junction of the cytotrophoblastic shell and decidua . cytotrophoblastic shell Syncytiotrophoblast Perforated by the spiral branches of the uterine vessels through which the maternal blood flows into the intervillous space. BASAL PLATE

20. B ounded on the inner side by the chorionic plate and the other side by the basal plate , limited on the periphery by the fusion of the two plates. L ined internally on all sides by the Syncytiotrophoblast and is filled with slow flowing maternal blood. Numerous branching villi which arise from the stem villi project into the space and constitute chief content of the intervillous space. INTERVILLOUS SPACE

21. Arise from chorion plate and extends to the basal plate. With progressive development primary, secondary and tertiary villi are formed. Functional unit of placenta (fetal cotyledon or placentome ) derived from a major stem villus. Functional subunit ( lobule)derived from a tertiary ste m villi. The total villi surface, for exchange , approx. varies between 10 to 14 sqms . The fetal capillary system within the villi is almost 50 km long. Blood vessels within the branching villi do not anastomose with the neighbouring one. STEM VILLI

22. IN THE EARLY PLACENTA Each terminal villus has got the following structure from outside inwards Outer Syncytiotrophoblast Cytotrophoblast Basement membrane Central stroma containing fetal capillaries, primitive mesenchymal cells , connective tissue and a few phagocytic cells. STRUCTURE OF A TERMINAL VILLUS

23. PLACENTA AT TERM Normal Placenta (At term) Diameter : 15 to 22 cm Thickness : 2.0 ~ 2.5 cm Weights : approximately 500 g (about 1 lb) Placental and fetal size and weight roughly correlate in a linear fashion. Fetal growth depends on placental weight which is less with small for gestational age infants - Heinonen and colleagues, 2001-

24. Placenta separates after the birth of the baby and the line of separation is through the decidua spongiosum . SEPARATION OF PLACENTA

25. Placental circulation consists of independent circulation of blood in two systems: Utero -placental circulation Feto -placental circulation A mature placenta has a volume of about 500ml of blood ,350ml being occupied in the villi system and 150 ml lying in the intervillous space. The blood of the intervillous spaces is replenished about 3 or 4 times per minute. CIRCULATION OF THE PLACENTA

26. Blood in the intervillous space is temporarily outside maternal circulatory system. It enters the intervillous space through 80 to 100 spiral endometrial arteries in the decidua basalis . These vessels discharge into the intervillous space through gaps in the cytotrophoblastic shell. Blood flowing from spiral arteries is pulsatile and is propelled in jet-like fountains by the maternal blood pressure. Welfare of the embryo and fetus chiefly depends on adequate bathing of branch villi with maternal blood. Reduction in utero-placental circulation result in fetal hypoxia and IUGR. MATERNAL PLACENTAL CIRCULATION

27. Poorly oxygenated blood leaves fetus and passes through umbilical arteries to the placenta. At the site of attachment of cord to placenta, these arteries divide into number of radially disposed chorionic arteries that branch freely in chorionic plate before entering chorionic villi. Blood vessels form extensive arterio -capillary-venous system within chorionic villi, brings fetal blood extremely close to maternal blood. FETAL PLACENTAL CIRCULATION

28. This system provides a very large area for exchange of metabolic and gaseous products between maternal and fetal blood streams. Well-oxygenated fetal blood in fetal capillaries passes into thin walled veins. This follow chorionic arteries to site of attachment of the umbilical cord, where they converge to form umbilical vein. This large vessel carries oxygen-rich blood to the fetus .

29. Development of uteroplacental vessels proceeds in two waves or stages. First wave occurs before 12 wks. post- fertilization and consists of invasion and modification of spiral arteries up to border between deciduas and myometrium. Second wave between 12 and 16 wks. involves some invasion of the intramyometrial segments of spiral arteries. Remodeling by this two-phase invasion converts narrow-lumen, muscular spiral arteries into dilated, low-resistance uteroplacental vessels. INVASION OF SPIRAL ARTERIES

30. Partition between fetal & maternal circulation. Not a perfect barrier. Thickness- ~0.025mm In early pregnancy it consists of-- Syncytiotrophoblast Cytotrophoblast Basement membrane Stromal tissue Endothelium of the fetal capillary wall with its basement membrane. PLACENTAL BARRIER

31. PLACENTAL BARRIER AT TERM Sparse cytotrophoblast & distended fetal capillaries almost fill the villus. Attenuation of syncytial layer. Thin ‘ alpha zones ’ also known as vasculo-syncitial membrane, where syncytiotrophoblast is thin & anuclear are for gas exchange. Thick ‘ beta zones’ with the layer remaining thick in patches containing extensive ER are for hormone synthesis.

32. Increase thickness of villus membrane found in IUGR & cigarette smokers. Basement membrane becomes thicker. Stroma contains dilated vessels along with all the constitute & few Hofbauer cells .

33. – Placental transfer – Metabolism – Hormone production – Haematopoietic – Immunological FUNCTIONS OF THE PLACENTA

34. RESPIRATORY-- Gaseous exchange [CO2, O2] – Passive diffusion across a pressure gradient – assisted by maternal hyperventilation [ progesterone effect] & fetal haemoglobin. Oxygen supply to the fetus @ 8ml/kg/min is achieved with cord blood flow of 165-330 ml/min. Placental transfer

35. EXCRETORY Waste products from fetus such as urea, uric acid & creatinine are excreted in maternal blood by simple diffusion. NUTRITIVE Glucose - facilitated diffusion Lipids - triglycerides & fatty acids directly transported from mother to fetus. Amino acids - active transport (amino acid concentration is higher in fetal blood than in maternal blood)

36. WATER AND ELECTROLYTES Na, K, Cl - simple diffusion Ca , P, Fe - active transport Water soluble vitamins - active transport Fat soluble vitamins - slow transfer (remains at low level in fetal blood)

37. HORMONES Insulin Adrenal steroids T hyroid hormones C horionic gonadotrophin or placental lactogen cross the placenta at a very slow rate to keep the fetal plasma concentration low. Parathormone Calcitonin d oes not cross the placenta.

38. Rate of metabolism similar to adult liver or kidney. Oxygen consumption is of same order as that of pancreas and kidney. Metabolic processes include: active glycolytic cycle, pentose phosphate pathway, tricarboxylic cycle, electron transmitter systems. More than 60 placental enzymes have been described. Placental metabolism

39. Diamine oxidase – inactivates the circulatory pressure amines. Oxytocinase – neutralises the oxytocin Phospholipase A2 - arachidonic acid synthesis.

40. Protein [polypeptides] Hormones 1. Human Chorionic Gonadotrophin – rises in 1st-early 2nd trimester, low levels after ~16 wks responsible for fetal adrenal cortex development Human Chorionic Somatotrophin – - fosters embryonic development by increasing fetal cell glucose absorption and stimulating lipid and CHO metabolism. Placental hormonal production

41. 3 . Human Placental Lactogen – - rises progressively from ~12 wks upt o term possibly useful in preparation for lactation contributes to diabetogenic effects of pregnancy 4. ACTH, TSH, M elanocyte Stimulating H ormone, R elaxin , Oxytocin, Vasopressin – All isolated from placental tissue but most likely are of maternal or fetal origin.

42. All rise progressively to plateau at term 1. Progesterone – Maintains pregnancy Maintains uterine quiesence mammary growth A ntialdosterone effect 2. Oestrogens ( oestriol ) – uterine growth & vascular supply to decidua & myometrium - metabolism & placental enzyme systems. 3. Androgens 4. Corticosteroids   Steroid Hormones

43. Placenta takes up Fe, V it . B12 & Folic acid  tendency towards anaemia in pregnancy. Fetal erythropoietin may cross placenta to mother since maternal reticulocyte counts are elevated in presence of fetal anaemia. Placental haematopoiesis

44. Feto -placental unit is an allograft that defies the foreign body tissue reaction. [ Type IV cell-mediated reaction] Fetus not antigenically mature. Placental immunology

45. Abnormal Shape or Implantation Degenerative Placental Lesions Circulatory Disturbances Hypertropic Placental Abnormalities Tumors of the Placenta PLACENTAL ABNORMALITIES

46. - Multiple placentas with a single fetus placenta bipartita or bilobata placenta duplex, triplex - succenturiate lobes - membranaceous placenta - ring – shaped placenta - fenestrated placenta - placenta accreta , increta & percreta - extrachorial placentation circumvallate placenta circummarginate placenta Abnormal shape or implantation

47. Abnormality Definition Clinical significance Multiple Placentas with a single fetus Placenta bipartita or bilobata - The placenta is separated into lobes - Division is incomplete and the vessels of fetal origin extend from one lobe to the other before uniting to form the umbilical cord Placenta duplex, triplex - Two or three distinct lobes are separated entirely and the vessels remain distinct. Bilobed Placenta Succenturiate lobes - Small accessory lobe ≥ 1, develop in the membranes at a distant from the periphery of the main placenta, to which they usually have vascular connections of fetal origin - Retained in the uterus after delivery and may cause serious hemorrhage - Accompanying vasa previa dangerous fetal hemorrhage at delivery

48. Abnormality Definition Clinical significance Membranaceous Placenta or Placenta Diffusa - All of the fetal membranes are covered by functioning villi and the placental develops as a thin membranous structure occupying the entire periphery of the chorion - Serious hemorrhage d/t associated placenta previa or accreta Ring – shaped Placenta - Placenta is annular in shape and sometimes a complete ring of placental tissue - Variant of membraceous placenta - Tissue atrophy in a portion of the ring a horseshoe shape in more common - Antepartum & postpartum bleeding and fetal growth restriction

49. Diagnosis Definition Clinical significance Fenestrated Placenta - Central portion of a discoidal placenta is missing - In some instances, there is an actual hole in the placenta but more often the defect involves only villous tissue with the chorionic plate intact - Mistakenly considered to indicate that a missing portion of placenta Placenta Accreta Increta Percreta - Serious variations in which trohpoblastic tissue invade the myometrium to varying depths - Much more likely with placenta previa or with implantation over a prior uterine incision or perforation - Torrential hemorrhage

50. Abnormalities of Placental invasion

51. Abnormality Definition Clinical significance Extrachorial Placentation Circumvallate Placenta Circummarginate placenta - When the chorionic plate, which is on the fetal side of the placenta, is smaller than the basal plate, which is located on the maternal side, the placental periphery is uncovered - Fetal surface of such a placenta presents a central depression surrounded by a thickened, grayish- white ring. - Ring : composed of a double fold of amnion and chorion with degenerated decidua and fibrin in between - Within the ring, the fetal surface present the usual appearance, except that the large vessels terminate abruptly at the margin of the ring - Ring dose not have the central depression with the fold of membranes - Antepartum hemorrhage from placental abruption and fetal hemorrhage - Preterm delivery - Perinatal mortaliy - Fetal malformations - Less well defined

52. Causes : Trophoblast aging or impairment of uteroplacental circulation with infarction. Deposition of calcium salts is heaviest on the maternal surface in the basal plate – → further deposition occurs along the septa and both increase as pregnancy progresses. Diagnosis : Sonography Degenerative placental lesions

53. Placental calcification

54. - Placental Infarctions - Maternal Floor Infarction - Placental Vessel Thrombosis Circulatory disturbances

55. Skriking enlargement of the chorionic villi is commonly seen in association with Severe erythroblastosis Fetal hydrops Maternal diabetes Fetal CHF Maternal-fetal syphilis Hypertrophic Lesions of Chorionic Villi

56. Gestational Trophoblastic Disease Chorioangioma ( hemangioma ) Tumours m etastatic to t he Placenta Embolic Fetal Brain Tissue Tumours of Placenta

57. CHORIOANGIOMA (HEMANGIOMA)

58. At term amnion is a tough, tenacious & pliable membrane. Innermost avascular fetal membrane. Contiguous with amnionic fluid. Provides almost all tensile strength. Lacks smooth muscle cells, nerves, lymphatics & blood vessels. THE AMNION

59. Bourne (1962) described five separate layers of amnion – - innermost single layer of cuboidal epithelium derived from embryonic ectoderm. - basement membrane - acellular compact layer, which is composed primarily of interstitial collagens fibroblast-like mesenchymal cells, derived from embryonic disc mesoderm - acellular zona spongiosa , contiguous with second fetal membrane, the chorion laeve Structure

60. Layers of Amniotic membrane

61. Early during implantation, a space develops between the embryonic cell mass and adjacent trophoblasts . Small cells that line this inner surface of trophoblasts have been called amniogenic cells— precursors of amnionic epithelium. The amnion is first identifiable about the seventh or eighth day of embryo development. It is initially a minute vesicle, which then develops into a small sac that covers the dorsal surface of the embryo. As the amnion enlarges, it gradually engulfs the growing embryo, which prolapses into its cavity. Development

62. Reflected amnion is fused to the chorion laeve . Placental amnion covers placental surface & thereby is in contact with adventitial surface of chorionic vessels. Umbilical amnion covers the umbilical cord. In the conjoined portion of membranes of diamniotic-dichorionic twin placenta, fused amnions are separated by fused chorion laeve . With diamniotic-monochorionic placenta, there is no intervening tissue between the fused amnions. ANATOMY

63. Meconium Staining Chorioamnionitis Other Abnormalities ABNORMALITIES OF THE MEMBRANES

64. Abnormalities Definition & causes Clinical significance Amnionic cyst Lined by typical amnionic epithelium Fusion of amnionic folds with subsequent fluid retention Amnion nodosum Tiny, creamy nodules in the amnion made up of vernix caseosa with hair, degenerated squames and sebum Oligohydramnios Found in fetuses with renal agenesis Prolonged preterm ruptured Membranes The placenta of the donor fetus with twin-to-twin transfusion syndrome Amnionic band Caused when disruption of the amnion leads to formation of bands or strings that entrap the fetus and impair growth and development of the involve structure Intrauterine amputation

65. C ord develops in yolk sac & umbilical vesicle which are prominent early in pregnancy. Embryo, at first, is a flattened disc interposed between amnion & yolk sac. Its dorsal surface grows faster than the ventral surface. E mbryo bulges into amnionic sac in association with elongation of neural tube. D orsal part of yolk sac is incorporated into the body of embryo to form gut. DEVELOPMENT OF THE CORD

66. Allantois projects into base of body stalk from the caudal wall of the yolk sac & later, forms anterior wall of hindgut. As pregnancy advances, yolk sac becomes smaller & its pedicle relatively longer. By about middle of 3 rd month, expanding amnion obliterates exocoelom , fuses with the chorion laeve , & covers the bulging placental disc & lateral surface of the body stalk. L atter is then called the umbilical cord— or funis . Cont..

67. It normally has two arteries and one vein . R ight umbilical vein disappears early during fetal development, leaving only the left vein. I ntra-abdominal portion of duct of umbilical vesicle, extending from umbilicus to intestine, usually atrophies & disappears. If patent, it is known as Meckel’s diverticulum . M ost common vascular anomaly - absence of one umbilical artery which may be associated with fetal anomalies . THE CORD AT TERM

68. U mbilical cord, or funis , extends from fetal umbilicus to fetal surface of placenta or chorionic plate. E xterior is dull white, moist, & covered with amnion, through which three umbilical vessels may be seen. D iameter - 0.8 to 2.0 cm. Average length of 55 cm with a range of 30 to 100 cm. Generally, cord length less than 30 cm is considered abnormally short. STRUCTURE OF THE CORD

69. Folding and tortuosity of vessels, which are longer than cord itself, frequently create nodulations on the surface, or false knots, which are essentially varices . The extracellular matrix is a specialized connective tissue referred to as Wharton’s jelly . Two arteries are smaller in diameter than the vein.

70. Length Cord Coiling Single Umbilical Artery Four-vessel cord Abnormalities of cord insertion Cord Abnormalities capable of impeding blood flow Hematoma Cysts UMBILICAL CORD ABNORMALITIES

71. Appreciable variation, extremes range – No cord( acordia ) ~ lengths up to 300cm Excessively long cords : ≥ 70cm ( ≥ 2 SD ) Length

72. Short umbilical cord Adverse perinatal outcomes – -fetal growth restriction - congenital malformations - intrapartum distress & risk of death (doubled) ( Krakowiak and associates,2004) Excessively long cord Associated with -maternal systemic disease -delivery complications - c ord prolapse, cord entanglement -fetal anomalies and respiratory distress Perinatal mortality : nearly threefold  

73. Umbilical vessels: in a spiraled manner Hypocoiled cords - in various adverse outcome in fetuses - meconium staining, preterm birth and fetal distress Hypercoiled cords - higher incidence of preterm delivery & cocaine abuse - Rana and associates (1995)   Cord coiling

74. Umbilical cord –2 arteries - 1 vein Risk factors – omen with GDM, PIH, APH, epilepsy, oligohydramnios & hydramnios . ¼ of all infants with only 1 artery have associated congenital anomalies.   Single umbilical artery

75. Diagnosis - routine ultrasound screening Prognosis - depends on whether 2 vessel cord is associated with other abnormalities or whether it is an isolated finding When a 2 vessel cord is an isolated finding aneuploid ≥ ½ Renal aplasia , Limb-reduction defects, Atresia of hollow organs in such fetuses, suggesting a vascular etiology Growth restriction did not occur in anatomically normal fetus with a single artery Goldkrand and associates (2001)

76. Venous remnant in 5% Significance : unknown Four – vessel cord

77. Usually inserted at or near center of fetal surface of placenta Furcate insertion Marginal insertion Velamentous insertion Vasa previa ABNORMALITIES OF CORD INSERTION

78. Abnormalities Definition Incidence Significance Furcate insertion Umbilical vessels separate from the cord substance before their insertion into the placenta Rare Prone to twisting & thromboses as vessels lose their cushioning Marginal Inserion Battledore placenta: Cord insertion at the placental margin 7% at term Cord being pulled off during delivery of the placenta Velamentous Insertion Umbilical vessels separate in the membranes at a distance from the placental margin Reach surrounded only by a fold of amnion 1.1% More frequently with twins 28% of triples

79. Velamentous Insertion

80. Associated with velamentous insertion when some of the fetal vessels in the membranes cross the region of the cervical os below the presenting fetal part Associated with - Velamentous insertion (50%) - Marginal cord insertion - Bilobed or Succenturiate -lobed placentas (50%) Risk factors - Bilobed , Succenturiate or low-lying placenta (80%) - Multifetal pregnancy - Pregnancy resulting from in vitro fertilization VASA PREVIA

81. Diagnosis - Color Doppler examination Perinatal diagnosis : associated with increased survival Antenatal diagnosis : associated with decreased fetal mortality compared with discovery at delivery A ntepartum or intrapartum haemorrhage Detecting fetal blood - Apt test - Wright stain : smear the blood on glass slides stain the smears with Wright stain and examine for nucleated RBC : normally are present in cord blood but not maternal blood

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