Developmental Anat. Block A

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Developmental Anat. Block A
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Developmental Anatomy Block A
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  1. spontaneous generation theory
    • new life arises from slime and decaying mater
    • held from the time of Galen for nearly 1500 years
  2. Hippocrates
    father of medicine
  3. Aristotle
    founder of embryology
  4. de conceptu et generatione hominis
    theory that the fetus developed from a coagulation of blood and semen in the uterus (Jacob Rueff)
  5. preformation theory
    • sperm or ovum contain a germ that is completely formed but minute and invisible and expands to visible size and form during development
    • theory of Homunculus
  6. epigenesis theory
    • egg lacks internal organization, some outside force causes development through use of cells
    • theory holding the development is a gradual process of increasing complexity
  7. germ layer theory
    • all animal embryos are composed of three primary germ layers (von Baer)
    • ectoderm, mesoderm, and endoderm
  8. cell theory
    the body is composed of cells and cell products (Schleiden and Schwann)
  9. recapitulation theory / biogenetic law
    • ontogeny mimics phylogeny (Haeckel)
    • claims that each embyro in its development passes through abbreviated stages that resemble developmental stages of its evolutionary ancestors
  10. ontogeny
    • the complete developmental history of an individual being
    • describes the complete life period of an individual from fertilization to death
  11. phylogeny
    the complete developmental history of a species or group of animals
  12. advances in fertilization enhancement techniques
    • artificial insemination
    • in vitro fertilization
    • transplantation
  13. advances in prenatal diagnosis
    • CT scan
    • ultrasound
    • amniocentesis
    • chorionic villis sampling
  14. amniocentesis
    • to determine whether the baby's lungs are mature enough for an early delivery if you appear to be in premature labor or require an early delivery for any reason
    • to diagnose or rule out a uterine infection
    • most commonly done between 15-18 weeks
    • to determine whether the baby has genetic or chromosomal abnormalities
    • Rh sensitization, Down syndrome, other trisomies, spina bifida, anencephaly
  15. chorionic villus sampling
    • performed between 10-12 weeks under ultrasound observation
    • analysis of cells from chorionic villus enables the detection of over 200 diseases and disorders
    • performed transcervically or transabdominally
  16. prenatal surgery
    • surgical treatment of the fetus
    • requires understanding of congenital abnormalities and normal development is required
  17. neonate/newborn
    an infant aged 1 month or less
  18. infancy
    • earliest period of extrauterine life
    • ~ the first year after birth
  19. childhood
    • period from 13 months until puberty or sexual maturity
    • period between infancy and puberty
  20. puberty
    is the period between the ages of 12 and 15 years in girls and 13 and 16 years in boys during which secondary sexual characteristics develop and the capability of sexual reproduction is attained
  21. adolescence
    period from about 11 to 19 years of age, which is characterized by rapid physical and sexual maturation
  22. adulthood
    • attainment of full growth and maturity
    • generally reached between ages of 18 and 21 years
  23. embryo
    the developing individual from fertilization until the end of the 8th week
  24. fetus
    the developing individual in utero from the end of the 8th week until birth
  25. zygote
    the first diploid cell formed by the union of the sperm and ovum
  26. gestation
    the period of development prior to birth
  27. congenital abnormalities
    abnormalities or malformations detected at birth or shortly thereafter
  28. anomaly
    • marked deviation from the average or normal standard
    • congenital defect
    • may be structural or metabolic
  29. malformation
    • a morphological defect that results from abnormal developmental processes and usually causes a functional deficit
    • ex: interatrial septal defect
  30. variation
    • a morphological deviation from an assumed standard that causes no function deficit
    • ex: persisting median artery
  31. syndrome
    a packageof congenital abnormalities that occurs in several organ systems as a result of a single factor
  32. ontogenetic development
    development of a single individual in structure and function both prenatally and postnatally
  33. growth
    • increase in mass
    • due to protoplasmic synthesis, uptake of water or intercellular or intracellular deposits
    • an increase in size of a living being or any of its parts occuring in the process of development
  34. differentiation
    the modification and specialization of cells, tissue, and organs in structure or function during the course of development
  35. primordium
    • anlage
    • the first appearance of a differentiating structure
    • an aggregation of cells in the embryo indicating the first trace of an organ or structure
  36. embryology
    • a subspecialty of anatomy
    • the science of the origin and development of the organism from the fertilization of the ovum to the period of extrauterine life
    • is restricted to the developmental processes occuring during the prenatal period of life
  37. fetology
    • a subspecialty of obstetrics
    • encompasses the study, diagnosis, and treatment of the fetus in utero
  38. perinatology
    • maternal/fetal medicine
    • a subspecialty of obstetrics involving the diagnosis and treatment of the fetus/newborn from 20th week of gestation until 4 weeks after birth
  39. neonatology
    a subspecialty of pediatrics involving the study, diagnosis, and treatment of the newborn during the first four weeks after birth
  40. methods of aging the embryo/fetus using body measurements
    • greatest length
    • crown-rump length
    • crown-heel length
    • biparietal diameter
  41. greatest length
    used during embryonic period
  42. crown-rump length
    • sitting height
    • used during embryonic period
    • measure from head (crown) to buttocks (rump)
  43. crown-heel length
    • standing height
    • used during fetal period
  44. chorionic sac first seen
    visible on vaginal ultrasound at approximately 13 days (chorionic villi begin)
  45. beginning of heartbeat
    visible on vaginal ultrasound at 22+/- 1 day
  46. biparietal diameter
    the diameter of the fetal head as measured from one parietal eminence to the other
  47. true age
    • 38 weeks (266 days) counting from the time of fertilization or conception
    • used by embryologists (and this class)
  48. ovulation age
    true age + 1 day
  49. ovulation age
    true age + 1 to 3 days
  50. menstrual/ gestational age
    • true age + 14 days
    • 280 days
    • used by obstetricians
  51. methods of aging the embryo/fetus
    • true age
    • ovulation age
    • copulation age
    • menstrual/gestational age
  52. human diploid cells
    • 22 pairs of autosomes
    • 1 pair sex chromosomes

    23 pairs of chromosomes TOTAL
  53. human haploid cells
    • 22 autosomes
    • 1 sex chromosome

    23 chromosomes TOTAL
  54. mitosis
    process of cell differentiation through which a cell gives rise to two daughter cells, each of which is genetically identical to the parent
  55. meiosis
    • process of reduction division of chromosomes
    • takes place only in germ cells
    • reduces number of chromosomes from a diploid to a haploid state
    • consists of two divisions
  56. miosis
    pupil constriction
  57. how is meiosis different in the two sexes?
    • timing
    • end products
  58. spermatogenesis
    the sequence of events by which spermatogonia are transformed into mature sperm

    • first meiotic division begins at puberty
    • results in four haploid mature sperm
  59. spermiogenesis
    spermatid to sperm

    • loss of cytoplasm
    • gain of tail
    • formation of acrosome
  60. oogenesis
    sequence of events by which oogonia are transformed into mature oocytes

    • first meiotic division begins in early fetal life
    • results in one mature ovum
  61. results of meiosis
    • provide constancy of the chromosome number from generation to generation
    • allows random assortment of maternal and paternal chromosomes between the gametes
    • allows for crossing over of chromosome segments, producing a recombination of genetic material
  62. nondisjunction
    a defect in the separation of homologous chromosomes
  63. aneuplody
    difference in the number of chromosomes
  64. capacitation
    • hyperactivity of sperm
    • changes in surface membrane properties leading to the acrosome reaction
  65. acrosome reaction
    • complex molecular changes that result in perforations in the acrosome
    • allows for the release of hyaluronidase and acrosin from the acrosome
    • occurs in the female genital tract
  66. events of fertilization
    • passage of sperm through corona radiata
    • penetration of zona pellucida
    • zona reaction
    • fusion of the plasma membranes of the two gametes
    • completion of 2nd meiotic division of the oocytes with fomation of the female pronucleus
    • formation of male pronucleus
    • fusion of pronuclei forming the diploid zygote
  67. zona reaction
    • prevents polyspermia - occurs once the first sperm penetrates the zona pellucida and the ovum
    • change in properties of the zona pellucida
    • renders it impermeable to other sperms
    • results from action of lysozomal enzymes released from cortical granules
  68. results of fertilization
    • completion of the 2nd meiotic division of the secondary oocyte
    • restoration of the diploid number of chromosomes in the zygote
    • mixing of paternal and maternal chromosomes to ensure diversity of species
    • determination of chromosomal sex
    • initiation of cleavage
  69. When does implantation begin?
    • day 6
    • the blastocyst has made contact with the posterior lining of the uterus
  70.  cleavage
    • repeated mitotic divisions of the zygote
    • results in a rapid increase in the number of cells (2,4,8,16...)
  71. morula
    16 cell stage of division
  72. implantation
    • the zona pellucida must degenerate for implantation to occur
    • the blastocyst implants within the posterior superior wall of the uterus within the functional layer of endometrium
    • the trophoblast differentiates into the cytotrophoblast and syncytiotrophoblast
  73. blastocyst formation
    • occurs when fluid secreted within the morula forms a blastocyst cavity
    • the inner cell mass becomes the embyroblast (which becomes the embryo)
    • the outer cell mass is now the trophoblast (which becomes part of the placenta)
  74. by the end of the first week after fertilization
    • cytotrophoblasts and syncytiotrophoblasts are formed from the trophoblast
    • implantation has begun
    • hypoblast (primary endoderm) is formed
  75. by the end of the second week of fertilization
    • implantation is complete
    • formation of the bilaminar embryonic disc
    • formation of the chorionic villi
    • enough HCG produced for a positive pregnancy test
  76. primary yolk sac
    • primary umbilical vesicle
    • hypoblast + exocoelomic membrane
  77. chorion
    extraembryonic somatic mesoderm + syncytiotrophoblast + cytotrophoblast
  78. layers of endometrium
    • compact layer: densely packed connective tissue around the necks of uterine glands
    • spongy layer: edematous connective tissue containing the dilated, tortuous bodies of the uterine glands
    • basal layer: blind ends of uterine glands
    • compact layer + spongy layer = functional layer
  79. hyaluronidase
    enzyme needed to get sperm through the corona radiata
  80. acrosin
    enzyme needed for sperm to burrow through the zona pellucida
  81. where does fertilization take place?
    ampulla of the uterine tube
  82. path of sperm to egg
    seminiferous tubules - rete testis - efferent ducts - epididymis - vas deferens/ductus deferens - seminal vesicles - ejaculatory duct - penile urethra - vagina - cervix - uterus - fallopian tubes - ampulla
  83. When to consult MFM?
    • to assist with high risk pregnancies
    • to provide counseling for patients with genetic disorders or family history of genetic defects
    • to help prevent complications of labor and delivery with high risk patients
  84. high risk pregnancies
    hypertension, HIV, diabetes mellitus, kidney disease, multiple gestations, thyroid disease, advanced maternal age
  85. preconception care
    • maintain good control of medical conditions (tight glucose control)
    • take folic acid for prevention of neural tube defects
    • stop cigarette smoking and alcohol/drug use
    • early prenatal care to ensure good pregnancy outcome!
  86. ectopic pregnancy
    • abnormal implantation of blastocyst
    • not a viable pregnancy
    • must be removed from the tube with medication or surgery
  87. embryonic age
    dating begins at the time of conception or fertilization
  88. gestational/menstrual age
    • dating begins from the first day of last menstrual period
    • clinical method for dating pregnancies
  89. Naegle's Rule
    • estimated due date (for 28 day cycles)
    • count back 3 months from last menstrual period and add 7 days
  90. embryonic development
    • fertilization until day 56 (end of 8th week)
    • all major structures are beginning to form
    • crown-rump length can be measured
    • most accurate method of dating during this time is by ultrasound
  91. fetal development
    • begins at end of 8th week and ends at birth
    • differentiation and growth of organs
    • monitor appropriate growth and prepare for delivery
    • assessment of fetal age can be determined by a series of measurement called fetal biometry
  92. neonatal development
    from birth until 30 days of life
  93. perinatal period
    span of time encompassing 24 weeks (viability of fetus) until 30 days post-delivery
  94. first trimester
    defined as the first day of the last menstrual period through the end of the 13th week
  95. first trimester - fetal
    • embryonic development (through 8 WGA) is time for organogenesis; highly susceptible to teratogens (alcohol, accutane, etc)
    • fetal development (after 8 WGA) body length doubles, skull formation, intestines return to abdomen, sex can be determined at end of the trimester
  96. first trimester - maternal
    elevated levels of hCG and progesterone can cause amenorrhea, morning sickness, heartburn, constipation, fatigue, and sinus congestion
  97. first trimester - genetic tests
    • 1st trimester combined testing - serum markers plus ultrasound to test for Trisomy 21 (Down syndrome)
    • done between 10 and 13 WGA
    • includes pregnancy associated plasma protein-A (PAPP-A), human chorionic gonadotropin (hCG), nuchal translucency on ultrasound (>3.55 indicator of Trisomy 21)
    • 85% sensitivity rate with 5% false positive rate
  98. second trimester
    defined as 14-28 weeks gestation
  99. second trimester - fetal
    • extensive brain development
    • alveoli begin to develop, surfactant secreted
    • rapid increase in growth of fetus
    • fetal movements at 16-18 WGA
    • 24 WGA is considered viability
  100. second trimester - genetic tests
    • 2nd trimester testing - serum markers to test for Trisomy 21 and other genetic defects
    • done between 15 and 20 WGA, confirmed by ultrasound dating
    • 85% sensitivity rate with 7% false positive rate
  101. genetic test indicators: Trisomy 21
    • elevated Inhibin A
    • decreased AFP
    • elevated hCG
    • decreased estriol
  102. genetic test indicators: Trisomy 18
    decrease AFP, hCG, and estriol
  103. genetic test indicators: neural tube or abdominal wall defects
    increased AFP
  104. anencephaly
    a neural tube defect in which  the head of the neural tube fails to close, resulting in absence of a major portion of the brain, skull, and scalp
  105. hydrocephalus
    • "water on the brain"
    • accumulation of CSF in ventricles of the brain
  106. cleft lip and palate
    the lip and palate failed to fuse in the midline during development
  107. spina bifida
    failure of the neural tube to close at bottom
  108. atrial septal defect
    atria are not separated by septum, resulting in 3 chambers of the heart rather than 4
  109. duodenal atresia
    • "double bubble sign"
    • duodenum is closed off distally, resulting in air bubbles in the stomach and duodenum
  110. omphalocele
    intestines are midline and within a sac outside of the abdominal cavity (fail to return to abdominal cavity during second trimester)
  111. second trimester - maternal
    • increase in cardiac output and heart rate
    • greatest weight gain
    • risk for gestational diabetes
    • dermatologic changes - abdominal striae (stretch marks) and melasma (mask of pregnancy)
    • increased risk of urinary tract infection due to growth of the uterus
  112. third trimester
    defined as 28 weeks gestations until delivery
  113. third trimester - fetal
    • alveoli fully develop for pulmonary maturity
    • growth of the fetus continues and can be followed by repeating ultrasound measurements (fetal biometry)
  114. large for gestational age
    • excessive fetal growth
    • defined as >90% for that gestational age
    • possible causes include diabetes, prolonged gestation, maternal diet/obesity
  115. small for gestational age
    • defined as <10% for that gestational age
    • constitutionally small
    • growth restricted and small
    • not small but growth restricted relative to gestational age
  116. intrauterine growth restriction
    • I: inherited - chromosomal or genetic abnormalities
    • U: uterus - poor placental perfusion (diabetes, renal disease, lupus) or malformation of the uterine cavity
    • G: general - lower socioeconomic status (malnutrition, smoking, alcohol)
    • R: rubella - and other TORCH infections
  117. TORCH
    • Toxoplasmosis
    • Other infections (syphillis)
    • Rubella
    • Cytomegalovirus
    • Herpes simplex virus
  118. ultrasound growth assessment
    • biparietal diameter
    • head circumference
    • femur length
    • abdominal circumference
  119. third trimester - maternal
    • maternal weight gain slows down
    • total blood volume peaks around 32 weeks (development of anemia can become more obvious)
    • gestational diabetes and pre-eclampsia can occur
    • check for palpated fetal movements
  120. spontaneous abortion
    refers to a pregnancy that spontaneously ends before a fetus reaches  viability (20-22 weeks gestation)
  121. spontaneous abortion incidence
    • 10-15% of clinically recognized pregnancies
    • nearly 80% before 12 weeks gestation
  122. spontaneous abortion etiology
    • chromosome abnormalities account for about 50% of 1st trimester losses
    • nearly 90% of those are at 8 weeks or less
  123. spontaneous abortion risk factors
    • advanced maternal age
    • previous spontaneous abortion
    • smoking
    • multiparity
    • excess alcohol and caffeine intake
    • maternal weight - BMI <18 or >25
  124. fetal death
    death prior to delivery or extraction from the mother
  125. stillborn
    if death happens after perceived viability
  126. live birth
    birth of an infant with signs of life after separation from mother, irrespective of short or long term potential for survival
  127. infant mortality rate
    number of deaths during first year of life per one thousand live births during a given time period
  128. how to calculate infant mortality rate
    • 10000 live births
    • 70 infants die before their first birthday

    • 70/10000
    • infant mortality rate = 7
  129. infant mortality factors
    • infection: hygeine, handwashing, clean birth conditions, plumbing, HIV control
    • resuscitation: knowledge, warmth, "helping babies breathe"
    • nutrition: breastfeeding
  130. infant mortality rate: birthweight & race
    discrepancy due to both social and medical issues
  131. causes of infant mortality
    • congenital abnormalities - spina bifida incidence decreased with folic acid
    • prematurity - number has increased
    • SIDS - decreased by "back to sleep"
    • RDS - decreased through use of surfactant
  132. preterm
    delivery prior to 38 weeks gestation
  133. term
    delivery from 38-42 weeks gestation
  134. post-term
    delivery beyond 42 weeks gestation
  135. optimum survival
    occurs in infants born AGA at term
  136. prematurity
    • any birth prior to 38 weeks
    • survival may occur as low as 23 weeksgestation, but birth at such a gestational age is accompanied by a high risk of mortality and morbidity
  137. problems of prematurity: lungs
    • surfactant deficiency
    • incomplete alveolar development
    • clinically labeled respiratory distress syndrome (RDS)
    • pathologically labeled hyaline membrane disease (HMD)
    • may evolve over weeks to months to more chronic lung disease - bronchopulmonary dysplasia (BPD)
  138. problems of prematurity: cardiac
    • poor cardiac function
    • hypotension (low blood pressure)
    • persistant patent ductus arteriosus
  139. problems of prematurity: brain
    • intraventricular hemorrhage
    • immature network of blood vessesls prone to bleeding into the adjacent brain
    • diagnosed by head ultrasound
  140. problems of prematurity: skin
    • increased fluid losses
    • infection
    • low temperature
  141. problems of prematurity: other organ systems
    • liver - jaundice
    • blood - anemia
    • immunity - increased risk of infection
    • eye - retinopathy of prematurity
    • ear - hearing loss
    • intestine - necrotizing enterocolitis
    • kidney - erractic fluid / electrolyte balance
    • genitalia - undescended testes, inguinal hernia
  142. low birthweight
    born <2500 grams (~5lbs)
  143. very low birthweight
    born <1500 grams (~3 lbs)
  144. extremely low birthweight
    born <1000 grams (~2lbs)
  145. appropriate for gestational age (AGA)
    birthweight between 10-90th percentile
  146. small for gestational age (SGA)
    birthweight less than 10th percentile
  147. large for gestational age (LGA)
    birthweight above the 90th percentile
  148. intrauterine growth restriction
    • pattern of reduced fetal growth which may result in SGA status
    • various etiologies which determine long term outcome
    • IUGR
  149. congenital cytomegalovirus (CMV) infection
    • IUGR
    • "blueberry muffin" rash
    • deaf
    • hepatitis
    • anemia
    • thrombocytopenia
  150. fetal alcohol syndrome
    • IUGR
    • microcephaly
    • abnormal face
    • heart murmur - ventricular septal defect (VSD)
    • mental retardation
  151. infant of diabetic mother
    • LGA
    • hypoglycemia
    • respiratory distress
  152. congenital diaphragmatic hernia
    • AGA
    • respiratory distress
    • scaphoid abdomen
    • heart sounds displaced
  153. changes from fetal circulation
    • decreased pulmonary vascular resistance
    • increased systemic vascular resistance
    • blood in pulmonary artery enters lungs instead of ductus arteriosus
    • blood in right atrium enters right ventricle instead of going through foramen ovale
    • placental circulation ceases
  154. Apgar score
    • clinical assesment of transition from intrauterine to extrauterine life
    • objective 10 point score of infant's physiologic activity immediately after birth
    • 5 items - heart rate, respiratory effort, response to stimulus, muscle tone, color - scored from 0 to 2
  155. conceptus
    term referring to the embryo/fetus and associated extraembryonic fetal membranes
  156. four fetal membranes
    • chorion/placenta
    • amnion/umbilical cord
    • yolk sac
    • allantois
  157. zygote
    sperm + oocyte
  158. gestational sac
    amnion + chorion
  159. the "week of twos"
    • second week of development
    • trophoblasts differentiates into two layers - cytotrophoblast & syncytiotrophoblast
    • embryoblast forms two layers - epiblast and hypoblast
    • extraembyronic mesoderm splits into two layers - somatic and splanchnic mesoderm
    • two cavities form - amniotic sac and yolk sac(s)
  160. hydatidiform moles
    • sometimes the trophoblast develops and forms placental membranes although little or no embryonic tissue is present
    • results in degenerating chorionic villi that form cystic swellings
    • secrete high levels of hCG
    • most often, the result of an abnormal fertilized egg
  161. choriocarcinomas
    3-5% of hydatidiform moles develop into malignant trophoblastic lesions which can spread rapidly through lymphogenous or vascular metastasis
  162. hydatidiform mole formation
    • a single sperm fertilizes an ova with no genetic material in it (result of nondisjunction in meiosis)
    • two sperm fertlize an ova with no genetic material in it
    • two sperm fertilize an apparently normal ova
  163. hydatidiform mole epidemiology
    • 1/2000 pregnancies (rare)
    • 10X more prevalent in Asian women
    • higher prevalence in women younger than 17 and older than 30
  164. chorion
    extraembryonic mesoderm + two layers of trophoblast (cytotrophoblast and syncytiotrophoblast)
  165. primary chorionic villi
    syncytiotrophoblast tissue with a core of cytotrophoblast
  166. secondary chorionic villi
    • invasion of mesenchymal cells at core of primary chorionic villi
    • entire chorionic sac is covered with secondary chorionic villi
  167. tertiary chorionic villi
    mesenchyme in core of secondary chorionic villi differentiates into capillaries and associated blood cells
  168. mesenchyme
    • loosely organized polymorphous pluripotent tissue
    • blood vessels and cells frequently develop from this tissue
  169. placenta
    • "afterbirth"
    • the primary site of nutrient and gas exchange between mother and fetus
    • fetomaternal organ
  170. components of the placenta
    • fetal part: develops from the chorionic sac (chorion frondosum)
    • maternal part: develops from the endometrium (decidua basalis)
  171. fetomaternal organ
    tissue contributions from both fetus and mother
  172. functions of the placenta
    • protection: defends against anything harmful that may be circulating in the maternal blood from crossing into fetal circulation
    • nutrition
    • respiration: gas exchange
    • excretion: getting rid of waste products that build up in high levels of metabolism occuring in the fetus during growth and development
    • hormone production: hCG
  173. decidua
    • the functional layer of the uterine endometrium
    • layer that is sloughed off during menstrual flow
  174. regions of the decidua
    • decidua basalis
    • decidua capsularis
    • decidua parietalis
  175. decidua basalis
    • forms the maternal part of the placenta
    • between the chorionic vesicle and the myometrium
  176. decidua capsularis
    • superficial part of the decidua overlying the conceptus
    • closes in over the top of the implanting embryo
  177. decidua parietalis
    remaining endometrium lining the main cavity of the uterus
  178. decidual reaction
    • cellular and vascular changes in the endometrium that occur as the blastocyst implants
    • maternal reaction to the implantation process
  179. smooth chorion
    • bare, relatively avascular area
    • chorion laeve
    • chorionic villi cover the entire chorionic sac until the beginning of the 8th week
    • villi in the decidua capsularis become compressed, deprived of adequate blood supply, and degenerate
  180. cotyledon
    • "clumps" of decidua basalis
    • location where the villi are bathed in maternal blood, but fetal/maternal blood will not mix
  181. villous chorion
    villi associated with decidua basalis proliferate & branch profusely
  182. amniochorionic membrane
    • fusion of amnion and smooth chorion
    • amniotic sac enlarges faster than the chorionic sac
    • ruptures during labor
  183. most common cause of premature labor
    preterm rupture of amniochorionic membrane
  184. maternal/placental circulation
    • normally no intermingling of maternal and fetal blood
    • deoxygenated blood returns to the mother from the placenta through the two umbilical arteries
    • oxygen-rich blood flows from the mother to the placenta through the umbilical vein
  185. placental membrane
    • consists of extrafetal tissues separating the maternal and fetal blood
    • tertiary villi form stem villi which form branch villi
    • the main exchange between mother and fetus takes place through the branch villi
  186. functions of the placenta
    • metabolism - synthesis of glycogen, cholesterol, fatty acids (provides energy for the embryo/fetus)
    • transport of gases and nutrients - via simple diffusion, facilitated diffusion, active transport, or pinocytosis
    • endocrine secretion - hCG
  187. uterine growth during pregnancy
    • not pregnant - uterus in pelvis minor (anteversion)
    • 20 weeks pregnant - uterus up to level of umbilicus
    • 30 weeks pregnant - uterus up to level of epigastric region
  188. stages of labor
    • dilation
    • expulsion
    • placental stage
    • recovery
  189. appearance of placenta
    • discoid
    • hemochorial
    • maternal surface - attached to uterus, cotyledons
    • fetal surface - very smooth, slippery and shiny due to amnion, attached to umbilical cord
  190. accessory placenta
    minor projection of placenta
  191. placenta percreta
    • chorionic villi penetrate the full thickness of the myometrium to or through the perimetrium (into peritoneal cavity)
    • may require hysterectomy
  192. placenta accreta
    abnormal adherence of chorionic villi to the myometrium (muscular layer of the uterus)
  193. placenta previa
    • placenta covers internal os of uterus
    • may cause 3rd trimester bleeding or premature separation of the placenta
    • may require C section
  194. velamentous insertion of the umbilical cord
    • umbilical cord is attached to the amniotic and chorionic membranes not to the placenta
    • predispose to tearing hemorrhage
  195. battledore placenta
    umbilical cord attaches at periphery of placenta
  196. umbilical cord
    • two arteries: carrying deoxygenated blood
    • one vein: carrying oxygenated blood
    • surrounded by a large amount of connective tissue (Wharton's jelly)
  197. umbilical cord length
    • too long - prolapse or coil around fetus, possible knots
    • too short - premature separation of placenta
  198. amniotic sac
    • surrounds the embryo/fetus
    • gradually enlarges to obliterate the chorionic cavity and forms the epithelial covering of the umbilical cord
  199. amniotic fluid
    • clear watery fluid
    • produced in part by amniotic cells but derived primarily from maternal blood
  200. function of amniotic fluid
    • absorbs jolts
    • allows for fetal movement
    • prevents adherence of the embryo to the amnion
    • acts as a barrier to infection
    • permits normal lung development
    • acts a temperature regulator
    • involved in maintaining homeostasis of fluid and electrolytes
  201. oligohydramnios
    • low volumes of amniotic fluid for a particular gestational age
    • can cause fetal abnormalities (eg. pulmonary hypoplasia, facial defects, limb defects) due to mechanical compression of the fetus against the uterine wall
  202. causes of oligohydramnios
    • preterm rupture of the amniochorionic membrane
    • placental insufficiency with diminished placental blood flow
    • renal agenesis or obstructive uropathy (absence of fetal urine contribution to amniotic fluid reduces the volume)
  203. polyhydramnios
    • high volumes of amniotic fluid
    • in excess of 2000 ml when the fetus does not swallow the usual amount of amniotic fluid
  204. causes of polyhydramnios
    • severe anomalies of the central nervous system
    • esophageal atresia in which fetus is unable to swallow the amniotic fluid
  205. amniotic band syndrome
    • set of congenital birth defects
    • believed to be caused by entrapment of fetal parts (limbs or digits) in fibrous amniotic bands while in utero
    • results from tears in the amnion
  206. dizygotic twins
    • results from fertilization of two oocytes
    • DZ twins always have two amnions and two chorions (may be fused)
    • hereditary tendency
  207. monozygotic twins
    • have a single chorionic sac
    • have separate amnions, but share a placenta
    • develop from one zygote by division of the embryoblast (inner cell mass) of the blastocyst
  208. twin-twin transfusion syndrome
    • discordant twins
    • there is a shunt of arterial blood from one twin through arteriovenous anastomoses into the venous circulation of the other twin
  209. monozygotic conjoined twins
    • thoracopagus = joined in thoracic region
    • dicephalic = two heads
  210. prenatal diagnosis
    • diagnosis of abnormalities in fetal life
    • multidisciplinary field, though generally applied in maternal fetal medicine
  211. purpose of prenatal diagnosis
    • early detection of malformations & disorders
    • inform and educate of the presence (or absence) of a fetal disorder
    • offer choice
    • treat the disorder in utero
  212. indications for prenatal diagnosis
    • family history or prior history of congenital defect, cytogenetic defect, or single gene disorder
    • "advanced maternal age"
    • abnormal routine ultrasound
  213. congenital malformations
    • defects present at birth
    • does not imply anything about cause or pathology
  214. cytogenetic defects
    • chromosomal abnormalities
    • diagnosed by visually assessing karyotype
  215. single gene disorders
    • mutant DNA at the nucleotide level
    • diagnosed for molecular techniques
  216. advanced maternal age
    • 33-35+ years old
    • refers to the concept that fetal risk for certain disorders increases with increasing maternal age
  217. pathogenesis of AMA-associated disorders
    • maternal meiotic defect
    • usually meiosis I (the reduction step)
    • aneuploidy
  218. aneuploidy
    • abnormal chromosome number
    • trisomies & monosomies
  219. Trisomy 21
    Down Syndrome
  220. Trisomy 13
    Patau Syndrome
  221. Trisomy 18
    Edward Syndrome
  222. 45, X
    Turner Syndrome
  223. 47, XXY
    Klinefelter Syndrome
  224. autosomal trisomies
    • Down Syndrome (+21)
    • Patau Syndrome (+13)
    • Edward Syndrome (+18)
  225. sex chromosome aneuploidies
    • Turner Syndrome (45, X)
    • Klienfelter Syndrome (47, XXY)
  226. relative risk of trisomy disorders
    Trisomy 21 > Trisomy 18 > Trisomy 13
  227. AMA-related risk for fetal aneuploidy
    • at 33 yrs - 1/2%
    • at 35 yrs - 1%
    • at 40 yrs - 2%
    • at 50 yrs - 10%
  228. noninvasive prenatal diagnostic methods
    • have no risk for fetal loss
    • useful in any pregnancy, even those without any increased risks
    • screening methods
    • ultrasound
    • maternal serum screening (MSS)
  229. invasive prenatal diagnostic methods
    • have a risk for fetal loss
    • used only if indicated
    • diagnostic methods
    • chorionic villus sampling (CVS)
    • amniocentesis
  230. ultrasound
    • transvaginal best at 5-9 weeks
    • transabdominal at 17-20 weeks
    • standard test ~18-20 WGA
    • uses sound waves
    • no harm to fetus
    • nonstandard enhancements - 3D technology, fetal echocardiography
  231. ultrasound-detected isolated defects
    • neural tube defects (NTDs)
    • club foot
    • heart defects
    • cleft lip
  232. ultrasound-detected syndromic defects
    • ambiguous genitalia
    • polydactyly
    • omphalocele
  233. ultrasound-detected malformations that suggest chromosomal abnormalities
    • nuchal thickness (NT) or edema
    • cystic hygroma
  234. limitations of ultrasound
    • sensitivity varies 20-80% depending on type of defect
    • better - NTDs; worse - facial and/or cardiac defects
    • best views of fetus not until >16 weeks
    • most single gene disorders have no physical malformations (normal prenatal ultrasound)
  235. maternal serum screening
    • tests maternal blood for fetal abnormalities
    • compares observed values to expected values
    • result given as a ratio - observed/expected
    • normal = 1
    • units - MoM (multiples of the median)
  236. first trimester MSS
    • 10-13 WGA
    • Pregnancy Associated Plasma Protein (PAPP-A)
    • human chorionic gonadotropin (hCG)
    • combined with ultrasound for nuchal thickness
  237. Down Syndrome: First Trimester MSS
    • low PAPP-A
    • high hCG
    • high NT
    • 85% detection rate
  238. Edward Syndrome: First Trimester MSS
    • low PAPP-A
    • low hCG
    • high NT
    • 87% detection rate
  239. second trimester MSS
    • "quad screen"
    • hCG: human chorionic gonadotropin
    • UE3: unconjugated estriol
    • AFP: alpha fetal protein
    • DIA: dimeric inhibin A
  240. Down Syndrome: Second Trimester MSS
    • high hCG
    • low UE3
    • low AFP
    • high DIA
    • 80% detection rate
  241. Edward Syndrome: Second Trimester MSS
    • low hCG
    • low UE3
    • low AFP
    • 80% detection rate
  242. NTD: Second Trimester MSS
    • high AFP
    • 80% detection rate
  243. Down Syndrome: Combined MSS
    • low PAPP-A
    • high hCG (x2)
    • high NT
    • low UE3
    • low AFP
    • high DIA
    • 97% detection rate
  244. Edward Syndrome: Combined MSS
    • low PAPP-A
    • low hCG (x2)
    • high NT
    • low UE3
    • low AFP
    • 97% detection rate
  245. limitations of MSS
    • carries a false-positive rate in addition to false-negative
    • explanation of results time consuming, complex
    • calculation of risk relies on accurate maternal data (gestational age, diabetes, ethnicity, etc.)
    • screens for only a few disorders
  246. MSS for fetal DNA
    • fetal DNA detectable in maternal blood <9 WGA
    • initially available for gender and gender-related conditions
    • eventual use in PNDx of fetal aneuploidy will follow
  247. amniocentesis
    • outpatient procedure
    • > 15 WGA
    • ultrasound guided percutaneous needle in amniotic fluid
    • 30cc of amniotic fluid aspirated
    • turn-around time for results = 2 wks
    • risk of miscarriage = 1/2 to 1%
  248. chorionic villus sampling
    • outpatient procedure
    • 10-12 WGA
    • ultrasound guided percutaneous or transcervical catheter into villi of chorion (tissue biopsy)
    • turn-around time for results = 1 wk
    • risk of miscarriage = 1%
  249. uses of CVS and amniocentesis
    • chromosomal testing (karyotyping or fluorescence in situ hybridization)
    • DNA testing for single gene disorders via molecular techniques
    • amniotic fluid AFP testing for open NTDs
  250. limitations of CVS and amniocentesis
    • 2% of CVS cytogenic analyses are ambiguous and require a follow up amniocentesis
    • many genes/mutations are unknown
    • must know gene/mutation of interest to give information about specific disorders
    • not routine
  251. NTDs
    • usually isolated birth defect
    • >90% detectable with ultrasound
    • 80% detectable with 2nd trimester MSS
    • diagnosis usually made with noninvasive techniques
  252. Down Syndrome
    • associated with AMA
    • risk is 1% at 40 years
    • 97% detectable with integrated MSS
    • diagnosis is invasive with CVS, AOC
  253. cystic fibrosis
    • autosomal recessive, single gene disorder
    • #1 lethal inherited disease in caucasians (f508 mutation)
    • prenatal diagnosis is invasive via CVS, AOC
  254. events in 3rd through 8th week of development
    • primitive streak formation
    • notochord formation
    • gastrulation
    • formation of three germ layers
    • differentiation of mesoderm
    • neurulation
    • early development of cardiovascular system
    • embryonic folding
    • early development of gastrointestinal system
  255. period of organogenesis
    • 3rd - 8th weeks of development
    • when anlage of all organ systems occur
    • when embryo is most susceptible to tetratogens
  256. what organ system is most likely effected if the fetus is exposed to a tetratogen early in development?
    nervous system (neural tube defects)
  257. gastrulation
    • the process in which a gastrula develops from a blastula by the inward migration of cells
    • the beginning of morphogenesis
    • followed by organogenesis
  258. events of the 3rd week of development
    • bilaminar embryo is converted into a trilaminar embryo
    • gastrulation
    • the three primary germ layers are established
    • the basic body plan is established, including the physical construction of the rudimentary primary body axes
    • inductive interactions - hallmark of neurulation and organogenesis
  259. inductive interactions
    one tissue type induces another tissue type to develop into something
  260. neurulation
    formation of the neural tube, the precursor for the CNS
  261. the body axes
    • anteroposterior
    • dorsoventral
    • left-right axis
  262. anterior visceral endoderm
    • cells in the anterior (cranial) margin of the embryonic disc
    • expresses genes essential for head formation - establish cranial end of the embryo before gastrulation
  263. what is the first sign of gastrulation?
    formation of the primitive streak
  264. primitive streak
    • indicative of the anterior-posterior (craniocaudal) axis
    • longitudinally oriented streak going from the primitive node to the posterior aspect of the developing bilaminar embryo (cloachal membrane)
    • appears as a thickened band of epiblast cells on the dorsal surface of the embryonic disc (characterized by rapid proliferation)
    • establishes right/left sides and dorsal/ventral surfaces of the embryo
  265. primitive node
    • Hansen's node
    • reflects the craniocaudal axis
    • proliferation of epiblast cells  at cranial end of primitive streak
  266. dorsoventral axis
    • established by cellular and molecular mechanisms
    • primitive streak ventrolizes mesoderm under the influence of BMP4 + FGF
    • increased goosecoid expression dorsolizes mesoderm (chordin, noggin, and follistatin inhibit BMP4)
  267. left-right body axis
    • controlled by a cascade of genes produced by notochord, primitive streak, etc.
    • nodal - member of transforming growth factor beta superfamily
    • SHH (Sonic Hedgehog) - midline barrier; represses expression of left-sided genes
  268. three major processes of gastrulation
    • formation of the primitive streak
    • development of the notochord
    • differentiation of three germ layers
  269. BMPs
    • bone morphogenic proteins
    • essential in the process of gastrulation
  270. buccopharyngeal membrane
    • also called oropharyngeal membrane
    • point where hypoblast and epiblast have essentially fused
    • forms the mouth
  271. cloacal membrane
    forms the anus
  272. from what are all three germ layers derived?
    epiblast
  273. mesenchyme
    • embryonic connective tissue
    • ameboid
    • loosely organized
    • actively phagocytic
    • polymorphous
    • pleuripotent
  274. differentiation of epiblast cells
    • deep surface of epiblast undergoes heavy proliferation to form mesenchyme - mesenchyme forms undifferentiated mesoderm - becomes intraembyronic (embyronic) mesoderm
    • some epiblast cells displace hypoblast to form intraembryonic (embryonic) mesoderm
    • remaining epiblast cells form intraembryonic (embryonic) ectoderm
  275. sacrococcygeal teratoma
    • undifferentiated tissue resulting from primitive streak that does not degenerate and disappear by the end of the fourth week
    • most common tumor of newborns
    • more common in girls than boys
    • can be visualized in utero with ultrasound and CT
  276. primitive streak degeneration
    • primative streak forms mesoderm until early part of 4th week
    • length of primitive streak decreases as notochord increases
    • primitive streak will eventually degenerate and disappear by the end of the 4th week
    • caudal end of embryo will decrease in size
  277. function of the notochord
    • defines the primordial cranialcaudal axis of the embryo
    • provides some rigidity to the developing embryo
    • serves at the basis for development of the axial skeletom (bones of the head and vertebral column)
    • indicates the future site of the vertebral bodies
    • persists as the nucleus pulposis of the intervertebral discs
    • primary inductor in the early embryo - induces overlying ectoderm to thicken and form neural plate
  278. notochordal process
    • formation of some mesenchyme cells migrating cranially from the primitive node (primitive pit)
    • deep to the epiblast (overlying ectoderm)
    • grows cranial to the prechordal plate
  279. prechordal plate
    • where ectoderm is fused with endoderm
    • primordium of the oropharyngeal membrane
  280. notochord development
    • primitive pit proceeds cranially into the notochordal process to form the notochordal canal
    • floor of notochordal process fuses with underlying embryonic endoderm
    • fused layers degenerate - form opening for communication with yolk sac
    • notochordal canal disappears & notochordal plate forms
    • notochordal cells proliferate & notochordal plate infolds to form definitive notochord
  281. neuroenteric canal
    • persistance of proximal notochordal canal
    • obliterated when notochord is complete
  282. split notochord syndrome
    • rare variant of neuroenteric cyst
    • AKA posterior spina bifida, combined spina bifida, neurenteric fistula, dorsal enteric fistula
    • primary notochord defect - the notochord is split, but not completely separated from the primitive intestine
    • syndrome manifests as a cleft in the dorsal midline of the body through which intestinal segments are exteriorized
  283. divisions of intraembryonic mesoderm
    • paraxial mesoderm
    • intermediate mesoderm
    • lateral mesoderm
    • extraembryonic mesoderm
  284. mesoderm formation
    • mesoderm formed from epiblast cells migrating (invaginating) through the primitive streak
    • mesenchymal intraembryonic mesoderm layer forms between ectoderm and endoderm with notochord down the midline
  285. derivatives of paraxial mesoderm
    • striated skeletal muscle
    • muscles of the head
    • skeleton (except cranium)
    • dermis of skin
    • connective tissue
  286. derivatives of intermediate mesoderm
    • urogenital system
    • gonads
    • ducts
    • accessory glands
  287. derivatives of lateral mesoderm
    • connective tissue
    • muscles of viscera
    • serous membranes of body cavities
    • primordial heart
    • blood and lymphatic cells
    • spleen
    • suprarenal cortex
  288. extraembyronic mesoderm
    • continuous with lateral mesoderm
    • outside of the embyro itself
  289. somite period of development
    • days 20-30
    • further development of paraxial mesoderm
    • segmenting of embyro
    • first appear in future occipital region
    • develop craniocaudally
  290. intraembryonic coelom
    • further development of lateral mesoderm
    • formation and fusion of coelomic spaces forms intraembryonic coelom
    • intraembryonic coelom splits lateral mesoderm into intraembryonic somatic mesoderm and intraembryonic splanchnic mesoderm
  291. intraembryonic somatic mesoderm
    • superior to intraembryonic coelom
    • forms body wall and skeletal muscle
    • areas innervated via GSE/GSA
  292. intraembryonic splanchnic mesoderm
    • inferior to intraembryonic coelom
    • forms smooth muscles of developing gut
    • areas innervated via GVE/GVA
  293. function of neurulation
    • creates neural tube - gives rise to CNS
    • creates neural crest - migrates away from dorsal surface of neural tube, gives rise to a diverse set of cell types
    • creates definitive epidermis - covers over the neural tube once it is created
  294. neurulation
    the processes involved in the formation of the neural plate and neural folds and closure of the folds to form the neural tube
  295. what induces neural plate formation?
    sonic hedgehog (SHH) from notochord and adjacent mesoderm
  296. period of dorsal induction
    notochord induces the ectoderm lying dorsal to it to thick and become neuroectoderm forming the neural plate
  297. neuroectoderm
    • forms the neural plate
    • gives rise to the CNS (brain and spinal cord)
  298. vasculogenesis
    blood vessel formation
  299. angiogenesis
    endothelial tubes fuse to form vessels which fuse to form networks of vessels
  300. blood vessel formation
    mesenchyme cells - angioblasts - blood islands - develop endothelial lined lumen (flattened angioblasts) - cavities fuses to form networks of endothelial channels - vessels sprout by endothelial budding, fuse with other vessels - hemangioblasts develop from endothelial cells of vessels
  301. angioblasts
    • endothelial cell precursors
    • vessel forming cells
  302. blood islands
    isolated angiogenic cell clusters
  303. hemangioblasts
    blood cells developed from endothelial cells of vessels
  304. first sign of heart development?
    angioblastic cords
  305. cardiogenic field/area
    horseshoe-shaped endothelial-lined tube surrounded by myoblasts
  306. first organ system to reach a functional state?
    • cardiovascular system
    • by the end of 3rd week (on 21st or 22nd day), blood is circulating and heat begins to beat
  307. placental circulation
    • 2 arteries: carrying waste from the embryo back to placenta
    • 1 vein: carrying oxygenated blood & nutrients to embryo
  308. folding of the embryo
    • folding of the flat trilaminar embyro into a "cylindrical embryo"
    • folding in the median (head & tail) and horizontal (right & left) planes
  309. head & tail folds
    • occur at 21 days
    • folding in the medial plane
    • pinches embryo off from rostral and caudal end
    • helps incorporate the yolk sac into the midgut
    • brings heart into its normal location (inferior to oropharyngeal membrane)
  310. right & left lateral folds
    • occurs at 26 days
    • folding in the horizontal plane
    • pinches off embryo from either side
    • helps establish the body wall - defines boundaries of intraembryonic coelom
  311. neurulation
    process involved with the formation of the neural plate and neural folds & closure of the folds to form the neural tube
  312. accomplishments of neurulation
    • creates neural tube - anlage to CNS
    • creates neural crest cells - give rise to many different cell types
    • creates definitive epidermis - covers the neural tube once created
  313. molecular control of neurulation
    • notochord and adjacent paraxial mesoderm induce the overlying embryonic endoderm to form the neural plate by secreting Sonic Hedgehog
    • notochord produces noggin, chordin, and follistatin which block the action of BMP4 - allow the dorsal ectoderm to thicken and become neuroectoderm
    • WNT-3a and FGF (fibroblast growth factor) also induce neural plate to form hindbrain and spinal cord
  314. when does neurulation begin?
    day 18
  315. when is the most likely time period for syndromes to develop?
    3rd to 8th week
  316. when does organogenesis occur?
    3rd to 8th week
  317. syndrome
    package of congenital abnormalities that occur in several organ systems as a result of a single factor
  318. neural tube formation: day 18
    • edges of neural plate begin to elevate to form neural folds with an interventing neural groove
    • presomite stage
  319. neural tube formation: day 20
    • first pair of somites are seen at paraxial mesoderm
    • neural folds become prominent
    • somatopleure & splanchnopleure occur
    • intraembryonic coelom subdivides into pericardial, peritoneal & pleural cavites
  320. somatopleure
    association of somatic mesoderm with overlying ectoderm
  321. splanchnopleure
    association of somatic mesoderm with underlying endoderm
  322. neural tube formation: day 21
    • neural folds are prominent rostrally - first signs of brain development; almost ready to fuse in dorsal midline
    • neural crest cells move to either side because of differential growth
    • 3 somite stage
  323. neural tube structure
    • neural ectoderm becomes neural plate which has neural folds and a neural groove in between
    • neural folds fuse in midline to form the neural tube which separates it from the surface ectoderm
    • cells making up the walls of the neural tube thicken and multiply quickly - undergo specialization to form brain and spinal cord
    • neural canal undergoes massive differentiation to form ventricular system in brain
  324. primary neurulation
    formation of neural tube
  325. secondary neurulation
    secondary cavity formation at the caudal end of the neural tube to form the sacral spinal cord
  326. openings of the neural tube
    • lumen of the neural tube communicates with the amniotic cavity through the rostral and caudal neuropores
    • openings supply nutrients & energy to embryo
  327. closure of neuropores
    • day 25: anterior (rostral) neuropore closes
    • day 27: posterior (caudal) neuropore closes
    • closures coincide with establishment of vascualr system
  328. which somites form the spinal cord?
    • 4th somite inferiorly
    • upwards of the becomes brain
  329. neural tube formation: day 22
    • 5 somite embryo
    • Carnegie stage 10
  330. neural tube formation: day 24
    • 13 somite embryo
    • Carnegie stage 11
  331. formation of the spinal cord
    • wall of neural tube is thick, pseudostratified columnar neuroepithelium
    • neuroblasts are dividing rapidly
    • three neural tube layers develop - marginal zone, mantle zone, ventricular zone
    • thin root and floor plate & thick walls form the alar and basal plates
  332. subdivisions of the neural tube
    • marginal zone
    • mantle (intermediate) zone
    • ventricular (ependymal) zone
  333. marginal zone of neural tube
    • deep to meninges (derived from mesnchyme around neural tube)
    • mostly consists of fibers (white matter)
  334. mantle (intermediate) zone
    • gives rise to majority of neurons
    • grey matter, dorsal & ventral horns
  335. ventricular (ependymal) zone
    • adjeacent to neural canal
    • forms ventricular system of the brain & spinal canal
  336. alar plate
    • forms dorsal portion (horns) of mantle
    • sensory neurons: receives central processes; gives rise to axons that form ascending sensory pathways
  337. basal plate
    forms ventral horns of the spinal cord (motor neurons, GSE)
  338. sulcus limitans
    • groove that separates the dorsal sensory neurons from the ventral motor neurons
    • separates alar plate & basal plate
  339. from what do spinal ganglia derive?
    neural crest cells
  340. neuroblasts
    • from neuroepithelium
    • become different types of neurons as they develop processes - apolar, unipolar, bipolar, and multipolar neurons
  341. epemdymal cells
    neuroepithelial cells differentiate into epemdymal cells when they stop producing neuroblasts
  342. glioblasts
    • give rise to glia (support cells that seem to play an important role in the nervous system)
    • macroglia: astrocytes & oligodendrocytes (myelination in the CNS)
    • microglia: from mesenchye
  343. dorsal and ventral signaling in early CNS
    homeobox-containing transcription factors: Pax-3, Pax-7, Msx-1 and Msx-2 are expressed throughout the neural plate
  344. ventralization
    • notochord gives rise to SHH, which represses Pax-3 and Pax-7, increases expression of Pax-6, and initiates neural tube floor plate formation
    • Pax-6 has a ventralizing effect and induces cells on either side of the floor plate to become motor neurons
  345. dorsalization
    • overlying surface ectoderm expresses BMP-4 & BMP-7
    • dorsalizing inductive effect on adjacent neuroectoderm
    • causes increase in Pax-3, Pax-7, Msx-1, and Msx-2
    • results in formation of roof plate and alar plate
    • stimulates expression of a transcription fact called "slug" in future neural crest cells
    • induces formation of sensory neurons in the alar plate after neural tube closure
  346. neural crest cell derivatives
    • spinal or dorsal root ganglion
    • adrenal medulla
    • mesenchyme - CT in head and neck
    • arachnoid & pia - leptomeninges
    • cranial nerve ganglia
    • melanocytes
    • C cells of the thyroid gland
    • conotruncal septum in the heart
    • schwann cells - myelin in PNS
    • oligodendrocytes - myelin in CNS
    • glial cells
  347. neurocristopathies
    defects in neural crest cell migration or morphogenesis
  348. major neurocristopathies - trunk NCC
    Hirschsprung's disease (aganglionic colon)
  349. major neurocristopathies - cranial NCC
    • aorticopulmonary septation defects of heart
    • anterior chamber defects of eye
    • cleft lip and/or cleft palate
    • frontonasal dysplasia
    • DiGeorge syndrome
    • certain dental anomalies
  350. DiGeorge syndrome
    • cranial NCC neurocristopathy
    • hypoparathyroidism
    • thyroid deficiency
    • thymic dysplasia leading to immunodeficiency
    • defects in cardiac outflow tract & aortic arches
  351. major neurocristopathies - trunk & cranial NCC
    • CHARGE association/ syndrome
    • Waardenburg syndrome
  352. syndrome
    a "package" of congenital abnormalities that occur in several organ systems as a result of a single factor
  353. CHARGE syndrome
    • C: coloboma, failure of choriod fissure to close (pupil has keyhole appearance)
    • H: heart defects, Tetralogy of Fallot (most common)
    • A: atresi choanae, blocking of airway, cannot breathe through nose
    • R: retardation of growth & development, associated with sensory deficits, mental retardation
    • G: genitourinary problems, genital hypoplasia, undescended testes, small labia
    • E: ear abnormalities, unusally shaped ears, sensory or conductive hearing loss
  354. Waardenburg syndrome
    • autosomal dominant
    • family history of parent with Waardenburg syndrome
    • extremely pale blue eyes or heterochromia (1 blue & 1 brown)
    • partial albinism - white forelock (poliosis) of hair, early greying of hair
    • deafness (variable degree)
  355. tumors and proliferation defects of NCC
    • pheochromocytoma
    • neuroblastoma
    • medullary carcinoma of thyroid
    • carcinoid tumors
    • neurofibramatosis
  356. pheochromocytoma
    tumor of chromaffin tissue of adrenal medulla
  357. neuroblastoma
    tumor of adrenal medulla and/or autonomic ganglia
  358. medullary carcinoma of thyroid
    tumor of parafollicular (calcintonin-secreting) cells of the thyroid
  359. carcinoid tumors
    tumors of enterochromaffin cells of digestive tract
  360. neurofibramatosis
    • von Recklinghausen disease
    • peripheral nerve tumors
  361. albinism
    lack of melanocytes (derivative of NCCs)
  362. myelinating cells
    • both derive from NCC
    • schwann cells: myelinate PNS; one schwann cell surrounds one axon
    • oligodendrocytes: myelinate CNS
  363. when is CSF produced?
    about the 5th week
  364. congenital anomalies of CNS
    • may be caused by alteration in morphogenesis or histogenesis of nervous tissue
    • may be caused by developmental failures occuring in associated structures (notochord, somites, mesenchyme, & skull)
    • failure of closure of the neural tube
    • occurs most commonly in regions of the anterior & posterior neuropore
  365. rachischisis
    • closure defect of the spinal cord
    • results in chronic infection, motor & sensory deficits, disturbances in bladder function
  366. cranioschisis
    closure defect in the area of the brain
  367. congenital anomalies of the spinal cord
    • defective closure of the neural tube during the 4th week
    • defects of dorsal induction OR neural tube defects (NTDs)
    • also involve overlying tissue - meninges, vertebral arch, muscles & skin
    • NTDs are caused by genetic and/or environmental factors
  368. spina bifida
    • nonfusion of the embyronic halves of the vertebral arches
    • pedicles & lamina don't meet up
  369. types of spina bifida
    • spina bifida occulta
    • spina bifida cystica
    • spina bifida cystica with meningocele
    • spina bifida cystica with meningomyelocele
    • spina bifida cystica with myeloschisis
  370. spinal dermal sinus
    • indicates with region of closure of the caudal neuropore at the end of the fourth week
    • indicated by a posterior skin dimple in the median plane of the sacral region
  371. spina bifida occulta
    • defect in neural arch
    • failure of the embryonic halves of the arch to grow normally & fuse in the median plane
    • occurs in L5 or S1 vertebrae in about 10% of otherwise normal people
    • may be indicated by a small dimple or a tuft of hair
    • usually produces no clinical symptoms
  372. spina bifida cystica
    • involves protrusion of the spinal cord and/or meninges through a defect in the vertebral arch
    • called "cystica" because of cyst-like sac that is associated with these anomalies
    • occurs once in every 1000 births
  373. spina bifida with meningocele
    • when the sac contains meninges and cerebrospinal fluid
    • the spinal cord and spinal roots are in the normal position
    • usually no clinincal deficits
  374. spina bifida with meningomyelocele
    • the spinal cord and/or nerve roots are included in the sac
    • often associated with a neurological deficit below or inferior to the level of the protruding sac
    • may occur anywhere along the vertebral column, but are most common in the lumbar region
  375. spina bifida with myeloschisis
    • spinal cord is open because the neural folds failed to close in the fourth week
    • monitor alpha-fetoprotein levels, nutritional & environmental factors (vitamins & folic acid)
  376. positional changes in the spinal cord
    • first trimester - spinal cord extends the entire length of the body
    • after 8 weeks - vertebral column develops more rapidly than the spinal cord
    • spinal roots are anchored in place, elongate at the column lengthens
    • cauda equina: elongated lumbar and sacral roots
    • lumbar cistern: expanded portion of the subarachnoid space
  377. from what does the skeletal system develop?
    • mesoderm: particularly in the axial skeleton
    • neural crest cells: give rise to mesenchyme in head & neck (contributes to the skull)
  378. paraxial mesoderm
    lies on either side of the notochord between notochord & intermediate mesoderm
  379. intermediate mesoderm
    • gives rise to urogenital system
    • "intermediate mesoderm of Swartz"
  380. lateral mesoderm
    • becomes separated by coelomic spaces
    • coelomic spaces will join to form the intraembryonic coelom
    • divides into somatic mesoderm & splanchnic mesoderm
  381. somites
    • blocks of segmented paraxial mesoderm
    • develop during days 20-30
    • appear (cranial to caudal) as bead-like elevations on the dorsolateral surface on either side of the developing neural tube
    • direct correlation with number of somites & age of embryo
    • 20 days: 1-4 somites
    • 25 days: 17-20 somites
    • 30 days: 34-35 somites
  382. somatic mesoderm
    associated with the ectoderm
  383. somatopleure
    somatic mesoderm + ectoderm
  384. splanchnic mesoderm
    associated with endoderm
  385. splanchnopleure
    • splanchnic mesoderm + endoderm
    • will eventually contribute to the formation of the muscular walls of the gut
  386. differentiation of somites
    • dorsolateral dermomyotome
    • ventromedial sclerotome
    • both are found on either side of the developing neural tube (will become spinal cord)
  387. differentiation of dorsolateral dermomyotome
    • dermatome: becomes dermis of the skin
    • myotome: becomes myoblasts (muscle precursors)
  388. differentiation of ventromedial schlerotome
    schlerotome: will become vertebrae and ribs
  389. genes that control somite differentiation
    • SHH: causes the ventral part of the somite to form schlerotome
    • PAX1: controls chondrogenesis and vertebral formation
    • PAX3: demarcates the dermomyotome
    • Wnt proteins + Myf5: form epaxial (deep) back muscles
  390. SHH
    • Sonic Hedge Hog
    • secreted by notochord & floor plate of neural tube
    • causes basal cell plate to become motor neurons
    • causes ventromedial part of somite to form sclerotomes & express PAX1
  391. PAX genes
    • family of development control genes that encode nuclear transcription factors
    • PAX1: controls chondrogenesis & vertebral formation
    • PAX3: demarcates the dermomyotome
  392. types of bone formation
    • endochondral: mesenchyme becomes ossified to form cartilagenous precursor; cartilage will then be ossified to become bone
    • intramembranous: mesenchyme forms directly to bone
  393. interzonal mesenchyme
    differentiates into various structures depending upon its positioin & type of joint
  394. synovial joint
    • ex - elbow joint, knee joint
    • interzonal mesenchyme differentiates into different parts of the synovial joint according to location
    • peripheral: IM forms capsular & other associated ligaments
    • centrally: IM will undergo apoptosis & form the joint cavity
    • lining central cavity & articular surfaces: IM forms synovial membrane
  395. cartilaginous joint
    IM may form hyaline cartilage at costochondral junctions OR fibrocartilage in the pubic symphysis joint
  396. fibrous joint
    • ex - sutures of the skull
    • IM will become dense fibrous connective tissues
  397. axial skeleton
    • skull, vertebral column, ribs, sternum
    • develops from schlerotome during 4th week under influence of PAX1
  398. where are schlerotome cells found?
    • on either side of the notochord (form vertebral column)
    • surrounding the neural tube (form vertebral column)
    • in the body wall (form ribs)
  399. parts of schlerotome
    • cranial: loosely arranged part
    • caudal: densely arranged part
  400. differentiation of sclerotomes
    • most cranial portion of densely arranged cells - forms portion of the intervertebral disc (annulus fibrosis)
    • caudal portion of densely arranged cell - fuses with loosely arranged cells of next caudal sclerotome to form centrum of vertebral body (embryonic body of the vertebrae)
    • notochord in region of intervertebral disc - form nucleus pulposus (surrounded by annulus fibrosis)
    • rest of notochord - associated with centrum of developing vertebrae; will degenerate under normal circumstances
  401. enlarging chordoma
    very malignant, rapidly epanding tumor resulting from failure of notochord to degenerate
  402. myotomes
    • lie at the level of the intervertebral disc
    • lie across the articulation between two adjacent vertebrae (neural foramina)
    • allow movement of spinal cord
    • muscles must cross over a joint to be effective (except facial muscles)
  403. development of vertebral arch: 5 weeks
    • centrum forms surrounding notochord
    • costal process sticks out into body wall
    • vertebral foramen contains neural tube
    • surrounding neural tube is vertebral arch
  404. development of vertebral arch: 6 weeks
    • vertebra with chondrification centers (endochondral bone formation associated with areas of sclerotome)
    • one on each side of notochord
    • one on each costal process
    • one on each half of vertebral arch
  405. development of vertebral arch: 7 weeks
    • cartilaginous precursor gets primary ossification centers
    • vertebrae become bony - process regulated by HOX genes
    • one center surrounding notochord in centrum
    • one center on either half of vertebral arch
    • "napoleonic" vertebrae: three bony parts
  406. development of vertebral arch
    • mesenchyme around neural tube vertebral (neural) arch
    • mesenchyme in body wall forms costal processes that form ribs in the thoracic region (forms transverse process in other regions)
    • "napoleonic" vertebrae - centrum & two halves of vertebral arch
    • neurocentral joint between two halves of the arch
  407. neurocentral joint
    • between two halves of "napoleonic" vertebrae
    • analogous to epiphyseal plate in long bones
    • accomodates the still expanding neural tube & spinal cord
  408. when do the bony halves of the vertebral arch fuse?
    during the first 3-5 years
  409. Homeobox genes
    • evolutionarily conserved genes
    • found in all vertebrates
    • involved in early embryonic development & specify identity and spatial arrangements of body segments
    • code for proteins which bind to DNA & form transcriptional factors which regulate gene expression
  410. anomalies of the axial skeleton
    • accessory ribs in lumbar & cervical regions
    • congenital hemivertebra
    • spina bifida
  411. accessory ribs in lumbar & cervical regions
    • results from development of costal processes in lumbar or cervical region
    • usually located in lumbar region - often asymptomatic in this area
    • cervical rib syndrome
  412. cervical rib syndrome
    • accessory cervical rib
    • typically on C7
    • can put pressure on brachial plexus and/or subclavian vessels
    • symptoms - pulse weaker on one side
    • one reason for thoracic outlet syndrome
  413. fused ribs
    • aplasia
    • costal processes can fuse with each other
  414. congenital hemivertebra
    • often accompanies cervical rib formation
    • occurs if one of the two chondrification centers on either side of centrum fails to develop
    • may be caused by HOX gene mutation
    • one cause of scoliosis (lateral curvature of the spine)
    • in thoracic region - associated with abnormalities of the ribs (aplasia)
  415. types of spina bifida
    • spina bifida occulta
    • spina bifida cystica with meningocele
    • spina bifida cystica with meningomyocele
    • spina bifida cystica with myeloschisis
  416. focal hirsutism
    location of healed meningocoele or atretic meningocoele
  417. spina bifidia occulta
    • results from failure of fusion of the halves of the vertebral arch
    • marked externally by a dimple or tuft of hair
    • lower thoracic, lumbar, & sacral regions are most common (but cervical also possible)
  418. development of sternum
    • 6 weeks
    • sternal plates converge at ventral midline
    • sternal plates fuse in a cranial to caudal direction
    • sternal plates become segmented into different sections (sternebrae)
    • development produces variations in xiphoid process (bifid, perforated, etc.)
    • endochondral bone formation
  419. anomalies of sternum
    • pigeon chest: results from overgrowth of ribs; sternum protrudes forward
    • cleft sternum: results from incomplete fusion of sternal plates at midline
    • notching of xiphoid process: can be bifid
    • sternal foramen: sometimes occurs at the junction of 3rd & 4th sternebrae
    • ectopia cardis: form of cleft sternum; associated with herniation of thoracic viscera (heart)
  420. funnel chest
    • congenital defect of the diaphragm
    • NOT a problem with the sternum itself
    • diaphragm has a small central tendon attached to xiphoid process
    • if pulled excessively, lower end of sternum is greatly depressed
  421. bones of extremities
    • 5 weeks: mesenchymal condensations
    • 6 weeks: chondrified
    • 8 weeks: begin to ossify
  422. endochondral bone formation
    • by 12 weeks, primary ossification centers have appeared in all bones of the limbs
    • secondary ossification centers have appeared in the distal femur & proximal fibula during 9th month of pregnancy
    • all other seconday ossicification centers appear after birth
  423. four sources of limb tissue
    • lateral plate mesoderm: skeleton, tendons, ligaments, vasculature
    • somites (dermomyotome): musculature
    • neural crest: schwann cells, dorsal root ganglia, sensory axons
    • neural tube: motor axons
  424. HOX genes
    regulate the types and shapes of bones in the limb
  425. limb growth
    • apical ectodermal ridge: thickened ectodermal clumb of cells at tip of developing limb
    • limb formation is under control of fibroblast growth factors
    • upper limb develops before lower limb
    • "progress zone": highly active mitotic cells that cause lateral expansion of limb away from axis; maintained by FGF4 and FGF8
    • 5 weeks: digital rays appear
    • 6 weeks: chondrification centers appear
    • 8 weeks: various ossification centers form
  426. genes associated with skeletal defects
    • FGFR-1: Pfieffer syndrome
    • FGFR-2: Pfieffer syndrome, Apert syndrome, Crouzon syndrome
    • FGFR-3: achrondroplasia
  427. Pfieffer syndrome
    • mutations in FGFR1 & FGFR2
    • craniosynostosis
    • broad great toes & thumbs
    • cloverleaf skull
    • underdeveloped face
  428. Apert syndrome
    • craniosynostosis
    • underdeveloped face
    • syndactyly (fused hands or feet)
  429. Crouzon syndrome
    • craniosynostosis
    • underdeveloped face
    • no hand or foot defects
  430. clavicle formation
    • forms by intramembranous ossification
    • ONLY tubular bone which does this
    • later becomes endochondral ossification
    • begins to ossify before any other bone in the body
  431. cleidocranial dysostosis
    • congenital absense or incomplete formation of clavicle
    • can touch shoulders together
    • autosomal dominant
  432. achondroplasia
    • hypoplastic chondrodystrophy
    • impairment of cartilage development in the epiphyseal plates of bone
    • most common cause of dwarfism
    • autosomal dominant (FGFR3)
    • 1/10000 occurance rate
    • short limbs, large head, normal trunk, muscles develop normally, results in skin folds on thighs
  433. development of muscular system
    • all muscles of the body develop from the mesoderm
    • except the muscles of the iris, which develop from the ectoderm of the optic cup
    • striated muscles of the trunk: develop from myotomes (part of somite)
    • smooth muscle & cardiac muscle: develop from splanchnic mesoderm
  434. myotome divisions
    • epaxial division: epimere; supplied by dorsal rami of spinal nerves; develop into deep back muscles
    • hypaxial division: hypomere; supplied by ventral rami of spinal nerves; gives rise to muscles in limbs & body wall
  435. congenital absence of muscles
    • palmaris longus - most common occuring
    • trapezius
    • serratus anterior
    • quadratus femoris
    • pectoralis major - part of Poland syndrome (lack of axillary fold)
    • abdominal muscles - Prune belly syndrome
  436. rotation of limbs
    • 48 days: limbs extend ventrally, hand and foot plates face each other
    • 51 days: upper limbs bent at elbows & hands curved over thorax
    • 54 days: soles of feet face medially
    • 56 days: elbows now point caudally & knees cranially
    • upper limbs rotate 90* laterally so that thumbs enter anatomic position
    • lower limbs rotate 90* medially so that big toes enter anatomic position
  437. dermatome
    area of skin supplied by a single spinal nerve at its ganglion
  438. cutaneous nerve area
    • peripheral nerve field
    • area of skin supplied by a peripheral nerve
  439. critical period for limb development
    24 to 42 days after fertilization
  440. limb malformations
    • amelia: complete absence of limbs
    • meromelia: partial absence of limb or limbs
    • syndactyly: failure of tissue between the digital rays to degenerate
  441. limb development (general)
    • occurs during 4th or 5th week
    • development is cranial to caudal, so upper limb development occurs about two days before lower limb
    • apical ectodermal ridge interacts with mesenchyme to form "progress zone", forming hand & foot plates
    • digital rays form, then tissue in between breaks down to form digits
  442. causes of limb defects
    • genetic: some cases of polydactyly, syndactyly, brachydactyly, etc are autosomal dominant disorders; many limb defects are components of genetic syndromes
    • teratogenic: drugs & chemicals (thalidomide, dimethadione, retinoic acid, cadmium), viruses (ex. Rubella), radiation, hypothermia, & hyperthermia
    • mechanical: amniotic bands may cause disruption or amputation of part of a limb; fetal compression due to oligohydramnios; uterine defect
  443. limb anomalies
    • brachydactyly: abnormally short digits
    • hypoplasia of thumb
    • polydactyly: supernumerary finger or tow
    • partial duplication of foot or thumb
    • cleft hand or foot: absence of central digits (Lobster claw deformity)
    • syndactyly: cutaneous or osseous failure of tissue between digital rays to degenerate
    • bilateral talipes equinovaris: club feet; twice as frequent in males (1/1000 births)
  444. congenital  anomalies of skin development
    • ichthyosis: fish-like skin; failure of superficial epidermis to slough off (keratinization)
    • hemangioma/angioma: vascular anomalies; can be treated with laser therapy
    • port-wine stains: type of hemangioma; capillary deformation producing characteristic area of red or purple skin
  445. development of mammary glands
    • occurs in 6th week
    • mammary ridges: extend from axilla to groin
    • mammary glands develop from pair of mammary ridges
    • primordium invades mesenchyme, forms modified sweat gland
    • development occurs continuously
    • notable development at puberty and pregnancy
  446. variations of mammary glands
    • polymastia: extra breast; occurs along mammary ridge line
    • macromastia: abnormally large breast
    • micromastia: one breast is significantly smaller than the other
    • polythelia: extra nipples; occurs on mammary line; can occur in males
  447. primordium of heart
    angioblastic cords in cardiogenic area (evident at 18 days)
  448. primitive heart tube
    • angioblastic cords canalize to form two endocardial heart tubes
    • lateral folding of the embryo causes endocardial heart tubes to fuse & form primitve heart tube
  449. when does the heart begin beating?
    22 or 23 days after fertilization
  450. layers of primordial heart tube
    • primordial myocardium: external layer of embryonic heart formed by splanchnic mesoderm; becomes myocardium (muscular wall of heart)
    • cardiac jelly: gelatinous connective tissue secreted by myocardium separating external layer from internal layer
    • primordial endocardium: internal endothelial layer; becomes endocardium
  451. dilations & constrictions of primordial heart tube
    • truncus arteriosus: continuous cranially with aortic sac (from which aortic arches arise)
    • bulbus cordis: gives rise to conus arteriosus & conus cordis (smooth parts of R & L ventricles)
    • primitive ventricle
    • primitive atrium
    • sinus venosus: drains umbilical, vitelline & common cardinal veins
  452. veins of developing heart
    • umbilical veins: carry well oxygenated blood from placenta
    • vitelline veins: return poorly oxygenated blood from yolk sac
    • common cardinal veins: return poorly oxygenated blood from body of the embryo
  453. developmental heart looping
    • bulbus cordis & primitive ventricle grow faster than other regions
    • heart bends upon itself
    • ventricles grow inferior & to the left
    • venous portion grows superio & to the right
    • as heart elongates & grows, it invaginates into the pericardial cavity
  454. developing pericardial cavity
    • completely envelopes heart
    • dorsal mesocardium: initial mesentery suspension of heart to dorsal wall
    • transverse pericardial sinus: remnant of dorsal mesocardium; communication between R & L sides of cavity
  455. circulation through primordial heart
    blood from sinus venosus - primordial atrium - sinuatrial valves - atrioventricular canal - primordial ventricle - bulbus cordis - truncus arteriosus - aortic sac - aortic arches - dorsal aortae for distribution to embryo
  456. changes in sinus venosus
    • shifts from center to right side; grows & becomes
    • sinus venarum: smooth part of R atrium
    • coronary sinus
    • oblique vein of L atrium
  457. changes in primitive atrium
    • displaced anteriorly on right
    • becomes right auricle
  458. developmental origin of pulmonary veins
    MAGICALLY sprout from future L atrium
  459. separation of atrium & ventricle
    • myocardium & cardiac jelly induce endocardium to rapidly divide
    • endocardial cushions form on dorsal & ventral walls of AV canal
    • tissue is invaded by mesenchymal cells; AV endocardial cushions fuse
    • divides AV canal into right & left
    • endocardial cushions function as AV valves
  460. separation of atria
    • septum primum: grows from roof of primitive atrium to endocardial cushion; forms foramen primum
    • foramen primum closes with continued growth of septum primum as foramen secondum appears
    • septum secondum grows adjacent to septum primum (becoming wall of R atrium); forms foramen ovale
    • septum primum partially degrades; becomes valve of foramen ovale (prevents backflow of blood allowing bypass of R ventricle in utero)
  461. separation of ventricles
    • muscular IV septum: formed by median muscular ridge in floor of ventricle; grows toward AV cushions but leaves IV foramen open
    • membranous IV septum: formed by fusion of three compartments - right & left bulbar ridges & endocardial cushion; closes IV foramen
    • merges with spiraling aorticopulmonary septum (allows communication between pulmonary trunk & R ventricle; ascending aorta & L ventricle)
  462. defects in 2nd heart field
    • atrial septal defects
    • membranous septal defects
  463. ventricle septal defect
    • muscular VSD: hole in muscle as it grows up from floor
    • membranous VSD: endocardial cushion does not grow up all the way to IV septum at superior portion (severe)
  464. atrial septal defect
    • can occur anywhere foramen occur
    • patent foramen ovale
    • defect in muscular/membranous portion of septum
  465. common atrium
    • interatrial septum never fuses
    • no right/left atria (just one)
  466. persistant truncus arteriosus
    • spiraling aorticopulmonary septa doesn't come down
    • both ventricles empty into a common trunk
    • poorly oxygenated blood goes to lungs & heart
    • essentially - one hole opens to common ventricle
  467. tetralogy of Fallow
    • overriding aorta: dextro-position of aortic valves in L & R ventricles
    • pulmonary stenosis: narrowing of pulmonary trunk
    • ventricular septal defect
    • right ventricular hypertrophy
  468. aortic arch development
    • 1st & 2nd mostly regress
    • dorsal aorta between 3rd & 4th degenerate
    • 5th degenerates or never forms
    • distal portion of right 6th degenerates (why left & right recurrent laryngeal nerves have different positions)
  469. recurrent laryngeal nerves
    • right: becomes trapped under right subclavian artery with degeneration of right 6th aortic arch
    • left: stays below ductus arteriosus
  470. circulatory changes at birth
    • umbilical vein - ligamentum teres
    • ductus venosus - ligamentum venosum
    • foramen ovale - fossa ovalis
    • ductus arteriosus - ligamentum arteriosum
    • umbilical arteries - superior vescial arteries & medial umbilical ligaments
  471. coarctation of aorta
    • postductal: after ductus arteriosus; body experiences decrease in blood flow; collateral circulation develops in utero
    • preductal: before ductus arteriosus; flow to upper & lower extremities is fine; only at birth does body register inadequate blood flow in descending aorta; unable to develop good collateral flow
  472. double aortic arch
    • right dorsal aorta does not obliterate at 6th aortic arch
    • trachea & esophagus trapped between arches
    • transient occlusion during contractions
  473. right arch of aorta
    • normally goes left
    • right dorsal aorta persists (left dorsal aorta obliterates)
    • hopefully ductus arteriosus develops on right side
    • if ductus arteriosus persists on left side, retroesophageal right arch of aorta will trap esophagus & trachea
  474. umbilical vein
    • carries oxygenated blood from placenta
    • right umbilical vein obliterates
    • left umbilical vein anastomoses with ductus venosus to drain into IVC
  475. ductus venosus
    • shunts blood from umbilical vein to IVC
    • allows oxygenated blood to bypass the liver in utero
  476. foramen ovale
    • allows blood to flow in between atria
    • bypasses right ventricle in utero
  477. ductus arteriosus
    • allows blood to flow from pulmonary trunk to descending aorta
    • bypasses lungs in utero
  478. retroesophageal right subclavian artery
    originates from aorta rather than right brachiocephalic trunk
  479. patent ductus arteriosus
    • failure to close at birth
    • allows unoxygenated blood into descending aorta
  480. gross development of lungs
    pharyngeal arches - respiratory diverticulum - laryngotracheal groove - laryngotracheal diverticulum - larynx, trachea, bronchi, & lung
  481. structures derived from laryngotracheal diverticulum
    • tracheoesophageal septum
    • larynx
    • trachea (bronchi, lungs)
  482. pharyngeal arches
    • 6 pairs
    • lined by endoderm on internal aspect
    • ectoderm on external aspect
    • mesenchymal core (NCCs have invaded mesoderm)
  483. respiratory diverticulum
    • region in which lung development occurs
    • first sign of respiratory system development (4th week)
  484. laryngotracheal groove
    caudal to 4th pharyngeal pouch
  485. pharygeal pouch
    internal space between pairs of pharyngeal arches
  486. laryngotracheal diverticulum
    • growth of mesenchyme ventral & inferior to pharynx
    • endoderm: pulmonary epithelium, glands of lower respiratory tract
    • splanchnic mesoderm: connective tissue, cartilage, smooth muscle of trachea & lungs
  487. larynx development
    • cranial end of LT diverticulum differentiates
    • endoderm: laryngeal epithelium
    • 4th & 6th pharyngeal arches: arytenoid swellings, laryngeal cartilages, mesoderm & neural crest cells
  488. arytenoid swellings
    • derived from 4th & 6th pharyngeal arches
    • on either side of laryngeal inlet
    • occlude passage through larynx into trachea for a time during development
    • remodel/ "recanalize" during 10th week
  489. remodeling of arytenoid swellings foms:
    • arytenoid cartilages
    • epiglottis
    • true & false vocal cords
  490. epiglottis development
    • ventral aspect of 3rd & 4th pharyngeal arches
    • forms hypopharyngeal eminence
    • cranial - give rise to tongue
    • caudal - epiglottis
  491. laryngeal ventricles
    • bounded by mucous membranes
    • vesitubular folds
    • vocal folds
  492. trachea development
    • caudal end of LT diverticulum differentiates
    • endoderm: tracheal epithelium & glands, pulmonary epithelium
    • splanchnic mesoderm: tracheal cartilage, connective tissue, tracheal smooth muscle
  493. respiratory bud
    enlargement at distal end of LT diverticulum
  494. bronchi development
    • respiratory bud
    • main stem primary bronchi: L & R
    • secondary (lobar) bronchi: 2L & 3R
    • tertiary (segmental) bronchi/bronchopulmonary segments: 8L & 10R
  495. stages of lung maturation
    • pseudoglandular: 6-16 weeks
    • canalicular: 16-26 weeks
    • terminal sac: 26 weeks to birth
    • alveolar stage: 32 weeks to 8 yrs
  496. pseudoglandular stage
    • Lungs resemble exocrine glands with ducts
    • Cuboidal epithelial tissue in endoderm
    • Surrounding mesenchyme contains blood vessels & fibroblasts (collagen CT)
    • Terminal bronchioles & all major lung elements present EXCEPT no means by which respiration can occur
  497. canalicular stage
    • Cranial portion of developing lungs mature faster than caudal portion
    • Lumen of bronchi enlarge
    • Terminal bronchioles enlarge and branch → respiratory bronchioles
    • Respiratory bronchioles divide into 3-6 passages (alveolar ducts) with terminal sacs (primordial alveoli)
    • Massive vascular proliferation in mesenchyme-          Differentiation of type I and II pneumocytes
    • RESPIRATION POSSIBLE (though not efficiently)
  498. terminal sac stage
    • Respiratory bronchioles enlarge & divide
    • Epithelium of endoderm becomes more squamous-          Growth of capillary network → capillaries bulge into terminal sacs lined by type I pneumocytes (Blood-air barrier; provides adequate gas exchange)
    • Collagen & elastic fibers are deposited by endoderm
    • Type II pneumocytes present in high numbers → secretion of pulmonary surfactant
  499. alveolar stage
    • Genuine mature alveoli begin to form
    • Mesenchyme differentiates – elastin & collagen; smooth muscle cells
    • Squamous epithelial layer of endodermal cells
    • Thin type I pneumocytes, type II pneumocytes → secreting lots of surfactant
    • Capillaries bulge into aveolar sacs
    • GAS EXCHANGE through alveolocapillary membrane
  500. extrinsic factors of lung development
    • adequate thoracic space
    • fetal breathing movements
    • adequate amniotic fluid
  501. adequate thoracic space
    • needed for lungs to expand & grow
    • if inadequate, lungs will be smaller than normal
  502. fetal breathing movements
    • fetus ingests amniotic fluid, aspirates it into lungs & expels it against resistance
    • conditioning respiratory muscles
    • critical for normal development & maturation of lungs
  503. oligohydramnios
    • too little amniotic fluid
    • fetal breathing movements don't occur
  504. polyhydramnios
    • too much amniotic fluid
    • fetus does not recycle amniotic fluid
    • caused by tracheoesophageal fistula or esophageal atresia
  505. tracheoesophageal fistula
    • Abnormal communication between structures
    • Problem in the formation of the tracheoesophageal fold/septum
  506. esophageal atresia
    • Esophagus ends as a blind sac
    • Every time swallowing occurs, material is aspirated into trachea
    • Food vomited back up shortly after ingestions
  507. laryngotracheoesophageal cleft
    • Ventral trachea is not separated from dorsal esophagus
    • Fusion of tracheoesophageal fold/septum does not occur along entire length
  508. laryngeal atresia
    • Failure of larynx to “recanalize”
    • Prevents ingestion of amniotic fluid for lung development
  509. CHAOS
    • congenital high airway obstruction syndrome
    • negatively impacts lung development - can't ingest & aspirate amniotic fluid
    • partial cause - laryngeal atresia
  510. tracheal fistula
    small outgrowth of trachea in cervical region
  511. congenital diaphragmatic hernia
    • liver has passed through diaphragm
    • restricts thoracic space, lungs fail to grow properly
  512. respiratory distress syndrome
    • hyaline membrane disorder
    • type II pneumocytes die
    • not enough surfactant produced
    • causes rapid, shallow breathing; cyanosis

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