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Willams ch. 7 Fetal growth and Development

Willams ch. 7 Fetal growth and Development. 부산백병원 산부인과 R2 박영미. PHYSILOLGY OF THE FETUS. Amnionic fluid (1). Amnionic fluid is composed In early pregnancy : ultrafiltrate of maternal plasma Second trimester : extracellular fluid which diffuses through the fetal skin After 20weeks

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Willams ch. 7 Fetal growth and Development

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  1. Willams ch. 7 Fetal growth and Development 부산백병원 산부인과 R2 박영미

  2. PHYSILOLGY OF THE FETUS

  3. Amnionic fluid (1) • Amnionic fluid is composed • In early pregnancy : ultrafiltrate of maternal plasma • Second trimester : extracellular fluid which diffuses through the fetal skin • After 20weeks : fetal urine : the fetal kidneys start producing urine at 12wks, by 18wks are producing 7-14ml/d

  4. Amnionic fluid (2) • Amnionic fluid volume • Increaes by 10ml per week at 8weeks and up to 60ml per week at 21weeks • Declines gradually back to a steady state by 33weeks • The usual amnionic volume • 50ml at 12weeks • 400ml at midpregnancy • 1000ml at term

  5. Amnionic fluid (3) • Amnionic fluid serves to • Cushion – allowing musculoskeletal development • Protecting from trauma • Maintains temperature • Minimal nutritive function • Epidermal growth factor, EGF-like growth factors (transforming growth factor-α) • Ingestion of amnionic fluid into the lung and gastrointestinal tract -> promote growth and differentiation of these tissues

  6. Fetal circulation (1) • Oxygenated blood is brought to the fetus by the umbilical vein • The vein divides into the ductus venosus and the portal sinus • The ductus venosus is enter the inferior vena cava directly • It carries well-oxygenated blood directly to the heart • The portal sinus carries blood to the hepatic veins • Relatively deoxygenated blood from the liver then flows back into the inferior vena cava

  7. Fetal circulation (2)

  8. Fetal circulation (3) • The ventricles of the fetal heart work in parallel, not in series • Well-oxygenated blood enters the left ventricle through the foramen ovale -> supplies the heart and brain • Less oxygenated blood enters the right ventricle through the tricuspid valve -> supplies the rest of the body

  9. Fetal circulation (4) • Two separate circulations • by the structure of the right atrium depending on its oxygen content • The well-oxygenated blood -> along the medial aspect of the inferior vena cava • The less oxygenated blood -> along the lateral vessel wall

  10. Fetal circulation (5) • About 87% of blood exiting the right ventricle -> the ductus arteriosus -> descending aorta • only 13% of right ventricular output -> to the lung • The high pulmonary vascular resistance • Lower resistance in the ductus arteriosus • One third of the blood passing through the ductus arteriosus -> to the body • The remaining output -> return to the placenta through the two hypogastric arteries -> distally become the umbilical arteries

  11. Fetal blood (1) • Hemopoiesis

  12. Fetal blood (2) • As fetal development progresses : • circulating erythrocytes are smaller and nonnucleated • The first erythrocytes : nucleated,macrocytic • the volume of blood in the common fetoplacental circulation increase • Hemoglobin concentration rises • Midpregnancy : 12g/dL • By term : 18g/dL

  13. Fetal blood (3) • Erythropoiesis • Controlled by erythropoietin made by the fetus • Maternal erythropoietin does not cross the placenta • Produced in response to hypoxic stress • Bleeding, labor, isoimmunization • Influenced by testosterone, estrogen, prostaglandins, thyroid hormone, lipoproteins • Fetal liver – may be an important source until renal production begins

  14. Fetal blood (4) • Fetal blood volume • Blood volume of term normal infants : average of 78 mL/kg when cord-clamping • The blood volume of fetal origin in the placenta : average 45 mL/kg • Fetoplacental blood volume at term : approximately 125 mL/kg

  15. Fetal blood (5) • Fetal hemoglobin • During embryonic and fetal life, a variety of a and b chain precursors • The timing of the production of each of these early hemoglobin version corresponds to the site of hemoglobin production • Yolk sac : hemoglobin Gower 1, Gower 2, Portland • Liver : hemoglobin F • Bone marrow : normal hemoglobin A

  16. Fetal blood (6) • The switch : various embryonic Hb -> Hb A • methylation of the early globin genes • Diabetic women • Persistence of Hb F • Hypomethylation of the r-gene • Sickle cell anemia • r-gene remains unmethylated • Large quantities of fetal Hb

  17. Fetal blood (7) • Hb F bind more oxygen than Hb A • Hb A binds 2,3-DPG more avidly than Hb F : lowers the affinity of Hb A for oxygen • Lower concentration of 2.3-DPG of fetal Hb : increased oxygen affinity of the fetal erythrocyte • The amount of Hb F in fetal erythrocytes falls during the latter weeks of pregnancy • At term, about ¾ of the total Hb is Hb F

  18. Fetal blood (8) • Coagulation factors in the fetus • About 12 weeks • Normal, adult-type, procoagulant, fibrinolytic, anticoagulant proteins • at appreciably reduced levels • not cross the placenta • Factors : II, VII, IX, X, XI, XII, XIII, fibrinogen • Fetal fibnogen • as early as 5 weeks • differenet properites -> less compressible clot, lower degree aggregation compared with adult

  19. Fetal blood (9) • Despite this reduced coagulation factors, the fetus seems to be protected from hemorrhage, and fetal bleeding is a rare event • Cordocentesis : amnionic fluid thromboplastins and some factor in Wharton jelly combine to faciliate coagulation at the umbilical cord puncture site • Protein C, S, antithrombin III deficiency, or the Leiden (factor V) mutation : thrombosis, infarction • Stillbirth followed by maternal pulmonary embolism : protein S deficiency

  20. Fetal blood (10) • Fetal plasma proteins • Concentrations of plasma protein, albumin, lactic dehydrogenase, aspartate aminotransferase, r-glutamyl transpeptidase, alanine trasferase -> all increase with gestational age • At birth, the mean total plasma protein, albumin concentrations in fetal blood -> similar to maternal levels

  21. Fetal blood (12) • Immunoglobulin G • IgG transport begins at about 16weeks • The bulk of IgG from the mother is during the last 4weeks of pregnancy • Preterm infants : relatively poorly with maternal antibody • Adult values are not attained until 3years of age

  22. Fetal blood (11) • Immunocompetence of the fetus • In the absence of a direct antigenic stimulus (such as infection) -> almost total immunoglobulins in the fetus is immunoglobulin G -> IgG synthesized in the maternal compartment and transferred across the placenta by receptor-mediated processes in syncytiotrophoblast

  23. Fetal blood (13) • Immunoglobulin M • IgM is not transported from mother to ferus • Increased levels of IgM with congenital infection • Rubella • Cytomegalovirus • Toxooplasmosis • Adult levels are attained by 9 months of age

  24. Fetal blood (14) • Immunoglobulin A • IgA ingested in colostrum -> mucosal protection against enteric infection • IgA ingested with amnionic fluid before delivery

  25. Fetal blood (15) • Lymphocytes • B lymphocytes : in liver by 9weeks : in blood & spleen by 12weeks • T lymphocytes : leave the thymus at 14weeks • The newborn responds poorly to immunization • Deficient response of B cells to polyclonal activation • Lake of T cell proliferation

  26. Nervous system and sensory organs • The spinal cord extends • In the embryo : entire vertebral column • By 24 weeks : S1 • At birth : L3 • In the adult : L1 • Myelination of the spinal cord • Begins in the middle of gestation • Continues through the first year of life • Synaptic function • Developed by the eighth week

  27. Nervous system and sensory organs • At 10 weeks • Squinting • Opening the mouth • swallowing • Incomplete finger closure • complete finger closure during the fourth lunar month • 14-16 weeks • Respiration • After 24 weeks • The ability to suck • The third trimester • Integration of nervous and muscular function proceeds

  28. Nervous system and sensory organs • The development of internal, middle, external components of the ear -> by midpregnancy • The fetus hears some sounds in utero as early as 24-26 weeks • The eye sensitivity to light -> by 28 weeks • But, perception of form and color is not complete until long after birth

  29. Gastrointestinal tract (1) • Swallowing begins at 10-12weeks • Coincident with intestine peristalsis and glucose transport • What stimulates swallowing -> not clear • The fetal neural analog of thirst • Gastric emptying • Change in the amnionic fluid composition • Fetal taste buds • Late in pregnancy, the volume of amnionic fluid -> regulated by fetal swallowing • Term fetus : 200-760mL per day

  30. Gastrointestinal tract (2) • Movement of amnionic fluid through the gastrointestinal system • Enhance growth and development of the alimentary canal • The swallowed amnionic fluid • Contributes little to the caloric requirements • Contributes essential nutrients • Late in pregnancy, about 0.8g of soluble protein, approximately half albumin, each day

  31. Gastrointestinal tract (3) • Meconium • Composition of meconium • Undigested debris from swallowed amnionic fluid • Glycerophospholipid from the lung • Desquamated fetal cells • Lanugo • Scalp hair • Vernix • Meconium passage • Normal bowel peristalsis in the mature fetus • Vagal stimulation due to cord compression • Hypoxia -> arginine vasopressin -> stimulates the smooth muscle of the colon to contract

  32. Gastrointestinal tract (4) • Liver • liver enzyme levels increase with gestational age • Limited capacity for converting free bilirubin to bilirubin diglucuronoside • Most of the bilirubin is transferred to the maternal circulation through the placenta • The small fraction conjugated bilirubin -> excreted through the biliary tract into the intestine • Unconjugated bilirubin -> excreted into the amnionic fluid after 12weeks -> transferred across the placent

  33. Gastrointestinal tract (5) • Most of the cholesterol • -> produced in fetal liver • Glycogen • Second trimester : low concentration in fetal liver • Near term : rapid and marked increase to levels two- three times those in adult liver

  34. Gastrointestinal tract (6) • Pancreas • 9-10weeks : Insulin-containing granules • 12weeks : insulin in fetal plasma • hyperglycemia -> increasing plasma insulin • Newborns of diabetic mothers • Large for gestational age infants • 14weeks : amylase in amnionic fluid • 16weeks : Most pancreatic enzymes are present • Trypsin, Chymotrypsin, Phospholipase A, lipase

  35. Urinary system (1) • 2weeks : pronephros • 5weeks : mesonephros -> producing urine • 11-12weeks : mesonephros -> degeneration • 9-12weeks : ureteric bud and nephrogenic blastema -> metanephros • 14weeks : loop of Henle -> functional & reabsorption occurs • Until 36weeks : new nephrons

  36. Urinary system (2) • The kidney receive 2-4% of the cardiac output • Renal vascular resistance is high • The glomerular filtration fraction is low • The filtration rate increases with gestational age • 12weeks : less than 0.1mL/min • 20weeks : 0.3mL/min • Urine production start at 12weeks • 18weeks : 7-14mL/day • At term : 27mL/hr, 650mL/day

  37. Pulmonary system (1) • Anatomical maturation of the fetal lung • Pseudoglandular stage • 15-17weeks • The growth of the intrasegmental bronchial tree • Canalicular stage • 16-25weeks • The peripheral extension of bronchial cartilage plates • terminal bronchiole -> respiratory bronchioles -> multiple saccular ducts • Terminal sac stage • The alveoli -> primative pulmonary alveoli (terminal sac)

  38. Pulmonary system (2) • An extracellular matrix develops from proximal to distal lung segments until term • Extensive capillary network & lymph system develops • The type II cells start to produce surfactant • At birth, only 15% of the adult number of alveoli • The lung continues to grow, adding more alveoli up to about 8 years

  39. Pulmonary system (3) • Surfactant • Formed in the type II pneumonocytes • Multivesicular bodies -> Lamellar bodies -> surfactant • At birth, with the first breath • Air-to-tissue interface in the lung alveolus • Surfactant to uncoil from the lamellar bodies • Prevent alveolar collapse during expiration

  40. Pulmonary system (4) • Surfactant compositon • 80% : Phosphatidylcholines (lecithins) • 8-15% : phosphatidylglycerol • Reducing surface tension in the alveolus

  41. Pulmonary system (5) • Corticosteroids and fetal lung maturation • Cortisol, produced in the fetal adrenal glands • Natural stimulus for lung maturation • Augmented surfactant synthesis • Glucocorticosteroids • Administered in large amounts to the woman • At certain critical times during gestation • Effect an increase in the rate of fetal lung maturation

  42. Pulmonary system (6) • Respiration • Respiratory muscles movement of fetal chest wall • Detected by USG as early as 11weeks • Respiratory movement intense to move amnionic fluid in and out of the respiratory tract • At the fourth month

  43. Endocrine glands (1) • Pituitary gland : The fetal pituitary develops from two different sources • Adenohypophysis • From the oral ectoderm – Rathke pouch • Neurohypophysis • From the neuroectoderm

  44. Endocrine glands (2) • Anterior pituitary : differnetiates into five cell types : secrete six protein hormones • Lactotropes -> prolactin (PRL) • Somatotropes -> growth hormone (GH) • Corticotropes -> corticotropin (ACTH) • Thyrotropes -> thyroid stimulating hormone (TSH) • Gonadotropes -> luteinizing hormone (LH) -> follicle stimulating hormone (FSH) : 7weeks -> ACTH is first detected : 17weeks -> synthesize and store all pituitary hormones

  45. Endocrine glands (3) • Neurohypophysis • Well developed by 10-12weeks • Oxytocin, arginine vasopressin (AVP) • Conserve water • by actions largely at the level of lung & placenta (rather than kidney)

  46. Endocrine glands (4) • Intermediate pituitary gland • Only in the fetal pituitary gland • Disappeared before term, absent in adult • a-melanocyte stimulating hormone (a-MSH) • b-endorphin • The levels of a-MSH decrease progressively with gestation

  47. Endocrine glands (5) • Thyroid • Hormone synthesis by 10-12weeks • The placenta actively concentrates iodide on the fetal side • The fetal thyroid concentrates iodide more avidly than the maternal thyroid • Radioiodide, amount of ordinary iodide -> hazardous • Placental tissue and membranes • Prevent substantial passage of maternal thyroid hormones to the fetus • Rapidly deiodinating maternal T4 & T3 to reverse T3

  48. Endocrine glands (6) • The role of thyroid hormone • Normal development of virtually all fetal tissues, especially brain • Congenital hyperhyroidism • When maternal thyroid-stimulating antibody crosses the placenta • Tachycardia, hepatosplenomegaly, hematological abnormalities, craniosynostosis, growth restriction

  49. Endocrine glands (7) • Adrenal glands • Fetal adrenal glands : much larger in relation to total body size than in adults • Fetal zone of the adrenal cortex • Hypertrophied fetal zone • Involutes rapidly after birth • Aaldosterone • Near term, the cord plasma levels exceed those in maternal plasma • Renal tubules : relatively insensitive to aldosterone

  50. Fetal Gender

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