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Fetal Development Stages of Fetal Development In 38 weeks a fertilized egg matures from a single cell carrying all necessary genetic material to fully developed fetus ready to be born. Terms: • • • • • Ovum - from ovulation to fertilization Zygote - from fertilization to implantation Embryo - from implantation to 5-8 weeks Fetus - from 5-8 weeks until term Conceptus - developing embryo or fetus and placental structures throughout pregnancy Stages of Fetal Development • Preembryonic stage: fertilization through 2nd week – Fertilization; cleavage; morula – Blastocyst and trophoblast (see Box 10-1) – Implantation • Embryonic stage: end of 2nd week through 8th week – Basic structures of major body organs and main external features (see Table 10-1) • Fetal stage: end of the 8th week until birth (Table 10-1) Stages of Fetal Development Fertilization: The beginning of pregnancy. • Fertilization is the union of the ovum and a spermatozoon.(conception, impregnation or fecundation). • Fertilization occurs in outer 3rd of a fallopian tube, the ampullar portion. • Fertilization has a span of 72 hours (48 hours before ovulation plus 24 hours afterwards). • Ovum and surrounding cells are propelled into fallopian tube by cilia. • One ovum reaches maturity each month. • Ovum is capable of fertilization for only 24 hours (48 at the most). • Sperm reach the ovum and clusters around the protective layer of corona cells. • Hyaluronidase (proteolitic enzyme) is released by sperm and acts to dissolve the layer of protective cells. • One sperm is able to penetrate the cell membrane of the ovum. • Once it penetrates the zona pellucide the membrane becomes impervious to sperm. (Except in the formation of hydatidiform mole > abnormal growth). This is what I was trying to remember the other day in class!!!!! • Next the chromosomal material of ovum and sperm fuse and become a zygote. • 23 chromosomes each = 46 total • Fertilization depends on: – maturation of both sperm and ovum – ability of sperm to reach the ovum – ability of sperm to penetrate the zona pellucida and cell membrane and achieve fertilization. Implantation: • zygote migrates toward body of the uterus. • takes 3 to 4 days • during this time mitotic cell division, or cleavage, begins. • 1st cleavage occurs at about 24 hours. • continues at a rate of one every 22 hours. • the zygote reaches the body of uterus with about 16 to 50 cells. • bumpy appearance termed morula. • Morula continues to multiply as it floats free in the uterine cavity for 3 to 4 days. • Large cells collect leaving a fluid space surrounding an inner cell mass and is termed blastocyte. • This attaches to the uterine endometrium. • Trophoblast - cells in the outer ring. • Embryoblast - inner cell mass later forms the embryo. • Implantation occurs in 8 to 10 days after fertilization. • The blastocyte brushes against the rich endometrium (in secretory phase of menstrual cycle) • attaches to the surface of the endometrium adhesion • proteolytic enzymes dissolve tissues • settles down (burrows) into soft folds invasion • usually high posterior side of the uterus • if low = placenta previa • 50% of zygotes never achieve this. • A pregnancy ends in 8 to 10 days after fertilization, before the woman is aware of a pregnancy. • Vaginal spotting may occur with adhesion / invasion due to rupture of capillaries by the implanting trophoblast cells. • Once implanted the zygote is called an embryo. Decidua: • uterine endometrium grows in thickness and vascularity. • Will be discarded after the birth of the child. • 3 areas: – decidua basalis - directly under the embryo – decidua capsularis - stretches or encapsulates the surface of trophoblastmembranes – decidua vera - remaining portion of lining Embryonic and Fetal Structures • Embryo grows and pushes decidua capsularis like a blanket, enlargement, contacts opposite uterine wall, fuses with endometrium. • At birth this entire inner surface of the uterus is stripped away, leaving the organ highly susceptible to hemorrhage and infection. Embryonic and Fetal Structures Chorionic Villi: • Once implantation is achieved, trophoblastic layer of cells of blastocyst begins to mature rapidly. • 11th to 12th day miniature villi reach out from trophoblast into endometrium. • Central core of connective tissue contain fetal capillaries. • Syncytial layer produces hormones, hCG, HPL, estrogen, progesterone. Embryonic and Fetal Structures Placenta: (latin for pancake) • arises out of trophoblast tissue. • serves as fetal lungs, kidneys, GI, endocrine • growth parallels fetal growth: 15 to 20 cm in diameter and 2 to 3 cm in depth at term. • covers about 1/2 the surface of internal uterus Embryonic and Fetal Structures Circulation: • 12 th day of pregnancy maternal blood begins to collect • by 3rd week-oxygen, nutrients, fluid diffuse from mother through chorionic villi to villi capillaries to the developing embryo. • no direct exchange of blood between embryo and mother during pregnancy. • exchange is by selective osmosis through the chorionic villi. • Minute breaks do occur Embryonic and Fetal Structures • membrane is affected by maternal B/P, pH of fetal and maternal plasma. Cotyledon: • in a mature placenta there are about 30 separate segments. (networked) • 100 maternal uterine arteries supply the mature placenta. • blood flow through the placenta is about 50 mL/min. at 10 weeks to 500 to 600 mL/min at term. Embryonic and Fetal Structures • To accommodate increased blood flow arteries increase in size. • Mothers heart rate, total cardiac output, and blood volume increase to supply the placenta. Uterine perfusion: • placental circulation is most efficient when mother lies on her left side. • This lifts the uterus away from the inferior vena cava,preventing blood from being trapped in lower extremities. Embryonic and Fetal Structures • If the mother lies on her back the weight of the uterus on vena cava causes supine hypotension. • At term a placenta weighs 400 to 600g 1 lb. • A small or enlarged placenta suggests circulation to the placenta is compromised. • Women with diabetes may develop a larger than usual placenta from fluid collected between cells. Endocrine Function Human Chorionic Gonadotropin: • 1 st hormone to be produced. • found in maternal blood and urine shortly after implantation or first missed period for 100 days from trophoblast. • analyzed with urine pregnancy test. • negative within 1 to 2 weeks post delivery. • hCG functions to keep corpus luteum producing progesterone, if this fails or progesterone falls the endometrium will slough, Endocrine Function until 8th week outer layer of cells of placenta begins to produce progesterone. • hCG suppresses maternal immunologic response to not reject the placenta. Estrogen: • primarily estriol is produced as a second product of syncytial cells of placenta. • contributes to mammary gland development in preparation for lactation. Endocrine Function • stimulates uterine growth to accommodate fetus. • assessing amount of estriol in maternal serum was used to test fetal well being. Progesterone: • maintains endometrial lining of the uterus during pregnancy. • present in serum 4th week of pregnancy. • reduces contractility of uterine muscle during pregnancy(prevents premature labor) Endocrine Function Human Placental Lactogen: (HPL) • both growth-promoting and lactogenic properties. • produced by the placenta by 6th week of pregnancy and increases to peak at term. • it promotes mammary gland growth in preparation for lactation in the mother. • regulates maternal glucose, protein, and fat levels so adequate amounts are available to the fetus. Umbilical Cord • Formed from the amnion and chorion and provides a circulatory pathway connecting the embryo to the chorionic villi. • Function is to transport oxygen and nutrients to the fetus from the placenta and to return waste products from the fetus to the placenta. • 21 inches (53cm) long and 3/4 inch (2cm) thick. • One vein - carries blood from placental villi to the fetus. Umbilical Cord • 2 arteries - carrying blood from the fetus back to the placenta villi. • Wharton’s jelly - gelatinous mucopolysaccharide gives cord body and prevents pressure on the vein and arteries. • The outer surface is covered with amniotic membrane. • Blood can be withdrawn from the umbilical vein or transfused into the vein during intrauterine life for fetal assessment or treatment. • Rate is rapid 350 mL/min. at term. Umbilical Cord • Blood flow (blood velocity) can be determined by ultrasound. • The rapid rate of blood flow through the cord makes it unlikely that it will twist or knot enough to interfere with O2 supply. • 20% of births a loose loop of cord is found around the fetal neck (nuchal cord). • Smooth muscle is abundant in the arteries of the cord. • Constriction of muscles after birth Umbilical Cord contributes to hemostasis and helps prevent hemorrhage of the newborn through the cord. • The cord contains no nerve supply, so it can be cut at birth without discomfort to child or mother. Membranes and Amniotic Fluid • The chorionic villi on medial surface of the trophoblast gradually thin and leave the medial surface smooth this becomes chorionic membrane, the outer most fetal membrane - next to baby. • Once it becomes smooth, it offers support to the sac that contains the amniotic fluid. • The amniotic membrane (amnion) forms beneath the chorion and becomes adherent to the fetal surface of the placenta, and give that surface a typically shiny appearance. Membranes and Amniotic Fluid • no nerve supply: no pain when it ruptures. • Amniotic membrane acts to support and produce amniotic fluid. • It produces a phospholipid that initiates tha formation of prostaglandins which cause uterine contractions and maybe the trigger to initiate labor. • amniotic fluid is constantly being newly formed and reabsorbed, so it is never stagnant within the membranes. Membranes and Amniotic Fluid • Fetus continually swallows the fluid, it is absorbed across the fetal intestine into the fetal bloodstream. • Umbilical arteries exchange it across the placenta. Also by direct contact with fetal surface of the placenta. • At term amniotic fluid is 800 to 1,200 mL. • Excessive amniotic fluid-hydramnios (>2,000mL) this occurs in women with diabetes R/T hyperglycemia (fluid shift into amniotic space). Membranes and Amniotic Fluid • Reduction in the amount of amniotic fluid oligohydramnios (<300) a disturbance of kidney function). • alkaline pH 7.2 • Protective: • shields against pressure or blow to mother’s abdomen. • protects fetus from changes in temperature. • aids in muscular development with allowing movement. • protects cord from pressure, protecting fetal oxygenation. Origin and Development From the beginning of fetal growth, development proceeds in a cephalocaudal (head to toe) direction. • Head first then middle and then lower body parts. This continues after birth also. • Body organ systems develop from specific tissue layers called germ layers. Primary Germ Layers: At the time of implantation, the blastocyte has separated to two cavities in the inner structure. Origin and Development • Amniotic cavity (large) - lined with a distinctive layer of cells called - Ectoderm. • Smaller cavity yoke sac which is lined with entoderm which supplies nourishment only until implantation. After that, it provides a source of red blood cells until the hematopoietic system is mature. • Ectoderm - CNS, PNS, skin, hair ,nails, sebaceous glands, sense organs, mucus membranes of the mouth, anus, nose, tooth enamel, mammary glands Origin and Development • Mesoderm (middle layer) – support structures - bone cartilage, muscle, ligament, tendon. Dentin of teeth, kidneys, ureters, reproductive system, heart, circulatory system, blood cells, lymph cells. • Entoderm (yolk sac) – lining of pericardia, pleura peritoneum, GI tract, respiratory tract, tonsils, parathyroid, thyroid, thymus, bladder,and urethra. Origin and Development Each germ layer of primary tissue develops into specific body systems. One reason rubella infection is so serious in pregnancy is because the virus is capable of affecting all the germ layers. All organ systems are complete at 8 weeks’ gestation (end of the embryonic period). Organogenesis: (organ formation) The growing structure is most vulnerable to invasion by teratogens. Cardiovascular System One of the 1st systems to become functional in intrauterine life. Simple blood cells joined to the walls of the yolk sac progress to a network of blood vessels and to a single heart tube forming as early as the 16th day of life, beating at 24th day, the septum divides during the 6th or 7th week, heartbeat may be heard with a doppler at 10th to 12th week. After the 28th week the heart rate begins to show a baseline of 5 beats/min. Cardiovascular System Fetal Circulation: • As early as the 3rd week of intrauterine life, fetal blood has begun to exchange nutrients with maternal circ across the chorionic villi. • Fetus derives O2 and excretes CO2 from the placenta (not lungs). • Blood enters the cells of lungs. • Specialized structures in the fetus shunt blood flow to brain, liver, heart,and kidneys. Cardiovascular System • Blood from the placenta is highly oxygenated. • Blood enters through the umbilical vein (called vein because the direction of blood flow is toward the fetal heart). • Carries blood to inferior vena cava through accessory structures - ductus venosus. • It receives O2 blood from the unbilical vein to supply the fetal liver. • Then, empties into the inferior vena cava. Cardiovascular System • From the inferior vena cava blood is carried to the right side of the heart. • As blood enters right atrium the bulk is shunted into the left atrium through an opening in the atrial septum the foremen ovale. • From the left atrium it follows normal circ. into the left ventricle and into the aorta. • Deoxygenated blood from the body is returned to the heart by the vena cava. Cardiovascular System • The blood enters the right atrium and leaves by the normal circ. route. • A large portion of this blood is shunted away from the lungs through an additional structure - ductus arteriosus which is directly into the aorta and then the descending aorta. • Most of the blood flow from the descending aorta is transported by the umbilical arteries (arteries even though they are transporting deoxygenated blood because they are carrying blood away from the heart). Cardiovascular System back through the umbilical cord to the placenta villi, where new O2 exchange takes place. • O2 saturation of the fetus is about 80% of the newborn’s saturation level. • Fetal heart rate - 120 to 160 beats/ min. is necessary to supply O2 to cells when RBC’s are never fully saturated. • CO2 does not accumulate because of rapid diffusion into maternal blood across a favorable placental pressure gradient. Cardiovascular System Fetal Hemoglobin: • Fetal hemoglobin has greater O2 affinity and is more concentrated. • Hemoglobin at birth - 17.1 g/100ml • Hematocrit - 53% • Sickle cell anemia - beta hemoglobin chain, symptoms do not appear for 6 months because hemoglobin matures then. Respiratory System • At the 3rd week respiratory and digestive tracts exist as a single tube. • Initially it is solid then canalizes. • Week 4 a septum begins to divide the esophagus from the trachea. • Week 6 lung buds may extend down into the abdomen. • Week 7 diaphragm becomes complete. • Week 24 and 28 - alveoli and capillaries begin to form. Both must be developed Respiratory System before gas exchange can occur in the fetal lungs. • Spontaneous respiratory begin at 3 months. • Specific lung fluid with low surface tension and low viscosity forms in alveoli to aid in expansion of alveoli at birth. • Surfactant a phospholipid substance is formed and excreted by aveolar cells about 24th week. This decreases alveolar surface tension on expiration, preventing alvolar collapse and improves respirations outside. Respiratory System • Surfactant has 2 components: – lecithin - 35th week increased production – sphingomyelin - early formation of surfactant • Surfactant mixes with amniotic fluid (L/S). • Lack of surfactant is a factor with RDS. • Interference of blood supply to the fetus causes increased production of surfactant. • Hypertension > increases stress increases steroid level associated with alveolar maturation. Nervous System • Week 3 and 4 formation begins. • Neural plate - a thickened portion of the ectoderm is apparent by 3rd week. Its top portion differentiates into the neural tube, which will form the CNS (brain and spinal cord), the neural crest, which develops into the peripheral nervous system. • Week 8 - brain waves can be detected on EEG. • All parts of the brain form in utero and growth continues after birth. Nervous System • Eye and inner ear develop as projections of the original neural tube. • Week 24 ear is capable of responding to sound • Eyes exhibit a pupillary reaction. • Very vulnerable to anoxia during the early weeks of the embryonic period, all during pregnancy and at birth. Endocrine System As soon as endocrine organs mature intrauterine life, function begins: • Adrenal glands supply a precursor for estrogen synthesis by the placenta. • Pancreas produces insulin needed by the fetus(does not cross the placenta from mother to fetus). • Thyroid and parathyroid glands play a vital role in metabolic function and calcium balance. Digestive System • Week 4 digestive tract is separated from the respiratory tract. • Grows rapidly from solid to a tube by canalization. • Endothelial cells of the GI tract proliferate, this occludes the lumens. • Intestines remain in the base of the cord until 10th week, then after abdominal cavity growth the intestine returns to the abdominal cavity. • Must rotate 180 degrees. Digestive System • 16th week meconium forms in the intestines • meconium consists of cellular wastes, bile fats, mucoproteins, mucopolysaccharides, portions of the vernix casosa, lubricating substances that form on the fetal skin. • It’s black or dark green and sticky. • GI tract is sterile before birth. • Vitamin K is synthesized by action of bacteria in the intestines. This causes low levels of vitamin K in newborns. Digestive System • Week 32 or the fetus weighs 1,500 g sucking and swallowing reflexes. • Week 36 the ability of the GI tract to secrete enzymes essential to carbohhydrate and protein digestion. • Amylase is not mature until 3 months after birth. • Lipase may not have developed yet. • Liver is active throughout gestation. – It functions as a filter between Digestive System the incoming blood and fetal circulation – deposit for stores of iron and glycogen, this is immature at birth. – This leads to hypoglycemia and hyperbilrubinemia in the first 24 hours after birth. Musculoskeletal System • Week 11 fetus can be seen to move on ultrasound (mother does not feel it yet) • Week 20 quickening - movement of the fetus. • Week 12 ossification of bone tissue begins and continues until adulthood. Reproductive System A child’s sex is determined at conception. • Week 6 gonads form (ovaries or testes). • If testosterone is present male organs develop. • In the absence of testosterone female organs develop. Urinary System Rudimentary kidneys are present by 4th week but are not essential before birth. • Week 12 urine is formed and excreted into the amniotic fluid by week 16. • At term fetal urine is 500mL/day. • The Loop of Henle is not fully differentiated until birth. Integumentary System • Skin of a fetus is thin and almost translucent until subcutaneous fat begins to be deposited about week 36. • Skin is covered by soft downy hairs (Lanugo) and a cream cheese like substance vernix casosa, which is important for lubrication and keeping the skin from macerating. Immune System IgG maternal antibodies cross the placenta into the fetus at 3rd trimester, giving temporary passive immunity. • Poliomyelitis, rubella, rubeola, diptheria, tetanus, mumps, pertussis. Not herpes. • Passive immunity peaks at birth and decreases over the next 8 months. At 2 months already has declined substantially. • Diphtheria, tetanus, pertussis, poliomyelitis, H influenzae are started soon after birth. • Measles last over 1 year. IgA and IgM antibodies cannot cross the placenta, if present the fetus was exposed to the disease.