Developing Human 9th Edition Moore Test Bank

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The Developing Human: Clinically Oriented Embryology, by Drs. Keith L. Moore, T.V.N. Persaud, and Mark G. Torchia, delivers the world’s most complete, visually rich, and clinically oriented coverage of this complex subject. Written by some of the world’s most famous anatomists, it presents week-by-week and stage-by-stage views of how fetal organs and systems develop, why and when birth defects occur, and what roles the placenta and fetal membranes play in development. You can also access the complete contents online at www.studentconsult.com, along with 17 remarkable animations, downloadable illustrations, additional review questions and answers, and more.

 

Table of Content:

  1. Chapter 1 Introduction to the Developing Human
  2. Developmental Periods
  3. FIGURE 1-1 Early stages of development. Development of an ovarian follicle containing an oocyte, ovulation, and the phases of the menstrual cycle are illustrated. Human development begins at fertilization, approximately 14 days after the onset of the last normal menstrual period. Cleavage of the zygote in the uterine tube, implantation of the blastocyst in the endometrium (lining) of the uterus, and early development of the embryo are also shown. The alternative term for the umbilical vesicle is the yolk sac; this is an inappropriate term because the human vesicle does not contain yolk.
  4. Abortion
  5. Significance of Embryology
  6. Historical Gleanings
  7. Ancient Views of Human Embryology
  8. Embryology in the Middle Ages
  9. FIGURE 1-2 Illustrations from Jacob Rueff’s De Conceptu et Generatione Hominis (1554) showing the fetus developing from a coagulum of blood and semen in the uterus. This theory was based on the teachings of Aristotle, and it survived until the late 18th century.
  10. The Renaissance
  11. FIGURE 1-3 Reproduction of Leonardo da Vinci’s drawing made in the 15th century AD showing a fetus in a uterus that has been incised and opened.
  12. FIGURE 1-4 Copy of a 17th-century drawing of a sperm by Hartsoeker. The miniature human being within it was thought to enlarge after the sperm entered an ovum. Other embryologists at this time thought the oocyte contained a miniature human being that enlarged when it was stimulated by a sperm.
  13. Genetics and Human Development
  14. FIGURE 1-5 Drawings illustrating descriptive terms of position, direction, and planes of the body. A, Lateral view of an adult in the anatomical position. B, Lateral view of a 5-week embryo. C and D, Ventral views of a 6-week embryo. E, Lateral view of a 7-week embryo. In describing development, it is necessary to use words denoting the position of one part to another or to the body as a whole. For example, the vertebral column (spine) develops in the dorsal part of the embryo, and the sternum (breast bone) in the ventral part of the embryo.
  15. Molecular Biology of Human Development
  16. Descriptive Terms in Embryology
  17. Clinically Oriented Problems
  18. References and Suggested Readings
  19. Chapter 2 First Week of Human Development
  20. Gametogenesis
  21. Meiosis
  22. Abnormal Gametogenesis
  23. Spermatogenesis
  24. FIGURE 2-1 Normal gametogenesis: conversion of germ cells into gametes (sex cells). The drawings compare spermatogenesis and oogenesis. Oogonia are not shown in this figure because they differentiate into primary oocytes before birth. The chromosome complement of the germ cells is shown at each stage. The number designates the total number of chromosomes, including the sex chromosome(s) shown after the comma. Notes: (1) Following the two meiotic divisions, the diploid number of chromosomes, 46, is reduced to the haploid number, 23. (2) Four sperms form from one primary spermatocyte, whereas only one mature oocyte results from maturation of a primary oocyte. (3) The cytoplasm is conserved during oogenesis to form one large cell, the mature oocyte. The polar bodies are small nonfunctional cells that eventually degenerate.
  25. FIGURE 2-2 Diagrammatic representation of meiosis. Two chromosome pairs are shown. A to D, Stages of prophase of the first meiotic division. The homologous chromosomes approach each other and pair; each member of the pair consists of two chromatids. Observe the single crossover in one pair of chromosomes, resulting in the interchange of chromatid segments. E, Metaphase. The two members of each pair become oriented on the meiotic spindle. F, Anaphase. G, Telophase. The chromosomes migrate to opposite poles. H, Distribution of parental chromosome pairs at the end of the first meiotic division. I to K, Second meiotic division. It is similar to mitosis except that the cells are haploid.
  26. FIGURE 2-3 Abnormal gametogenesis. The drawings show how nondisjunction (failure of one or more pairs of chromosomes to separate at the meiotic stage) results in an abnormal chromosome distribution in gametes. Although nondisjunction of sex chromosomes is illustrated, a similar defect may occur in autosomes. When nondisjunction occurs during the first meiotic division of spermatogenesis, one secondary spermatocyte contains 22 autosomes plus an X and a Y chromosome, and the other one contains 22 autosomes and no sex chromosome. Similarly, nondisjunction during oogenesis may give rise to an oocyte with 22 autosomes and two X chromosomes (as shown) or may result in one with 22 autosomes and no sex chromosome.
  27. FIGURE 2-4 Illustrations of spermiogenesis, the last phase of spermatogenesis. During this process, the rounded spermatid is transformed into elongated sperm. Note the loss of cytoplasm, development of the tail, and formation of the acrosome. The acrosome, derived from the Golgi region of the spermatid, contains enzymes that are released at the beginning of fertilization to assist the sperm in penetrating the corona radiata and zona pellucida surrounding the secondary oocyte.
  28. FIGURE 2-5 Male and female gametes (sex cells). A, The main parts of a human sperm (×1250). The head, composed mostly of the nucleus, is partly covered by the cap-like acrosome, an organelle containing enzymes. The tail of the sperm consists of three regions: the middle piece, principal piece, and end piece. B, A sperm drawn to approximately the same scale as the oocyte. C, A human secondary oocyte (×200), surrounded by the zone pellucida and corona radiata.
  29. Oogenesis
  30. Prenatal Maturation of Oocytes
  31. Postnatal Maturation of Oocytes
  32. Comparison of Gametes (sex Cells)
  33. Abnormal Gametes
  34. Uterus, Uterine Tubes, and Ovaries
  35. Uterus
  36. Uterine Tubes
  37. Ovaries
  38. Female Reproductive Cycles
  39. FIGURE 2-6 A, Parts of the uterus and vagina. B, Diagrammatic frontal section of the uterus, uterine tubes, and vagina. The ovaries are also shown. C, Enlargement of the area outlined in B. The functional layer of the endometrium is sloughed off during menstruation.
  40. FIGURE 2-7 Schematic drawings illustrating the interrelations of the hypothalamus of the brain, pituitary gland, ovaries, and endometrium. One complete menstrual cycle and the beginning of another are shown. Changes in the ovaries, the ovarian cycle, are induced by the gonadotropic hormones (follicle-stimulating hormone and luteinizing hormone). Hormones from the ovaries (estrogens and progesterone) then promote cyclic changes in the structure and function of the endometrium, the menstrual cycle. Thus, the cyclical activity of the ovary is intimately linked with changes in the uterus. The ovarian cycles are under the rhythmic endocrine control of the pituitary gland, which in turn is controlled by the gonadotropin-releasing hormone produced by neurosecretory cells in the hypothalamus.
  41. Ovarian Cycle
  42. Follicular Development
  43. FIGURE 2-8 Photomicrograph of a human primary oocyte in a secondary follicle, surrounded by the zona pellucida and follicular cells. The mound of tissue, the cumulus oophorus, projects into the antrum.
  44. FIGURE 2-9 Micrographs of the ovarian cortex. A, Several primordial follicles are visible (×270). Observe that the primary oocytes are surrounded by follicular cells. B, Secondary ovarian follicle. The oocyte is surrounded by granulosa cells of the cumulus oophorus (×132). The antrum can be clearly seen (*).
  45. Ovulation
  46. FIGURE 2-10 Illustrations of ovulation. Note that fimbriae of the infundiulum of the uterine tube are closely applied to the ovary. The finger-like fimbriae move back and forth over the ovary and “sweep” the oocyte into the infundibulum. When the stigma (swelling) ruptures, the secondary oocyte is expelled from the ovarian follicle with the follicular fluid. After ovulation, the wall of the follicle collapses and is thrown into folds. The follicle is transformed into a glandular structure, the corpus luteum.
  47. FIGURE 2-11 Illustration of the blood levels of various hormones during the menstrual cycle. Follicle-stimulating hormone (FSH) stimulates the ovarian follicles to develop and produce estrogens. The level of estrogens rises to a peak just before the luteinizing hormone (LH) surge. Ovulation normally occurs 24 to 36 hours after the LH surge. If fertilization does not occur, the blood levels of circulating estrogens and progesterone fall. This hormone withdrawal causes the endometrium to regress and menstruation to start again.
  48. Mittelschmerz and Ovulation
  49. Anovulation
  50. Corpus Luteum
  51. Menstrual Cycle
  52. Anovulatory Menstrual Cycles
  53. Phases of the Menstrual Cycle
  54. FIGURE 2-12 Sagittal section of the male pelvis showing the parts of the male reproductive system.
  55. Transportation of Gametes
  56. Oocyte Transport
  57. Sperm Transport
  58. Maturation of Sperms
  59. FIGURE 2-13 Acrosome reaction and sperm penetrating an oocyte. The detail of the area outlined in A is given in B. 1, Sperm during capacitation, a period of conditioning that occurs in the female reproductive tract. 2, Sperm undergoing the acrosome reaction, during which perforations form in the acrosome. 3, Sperm digesting a path through the zona pellucida by the action of enzymes released from the acrosome. 4, Sperm after entering the cytoplasm of the oocyte. Note that the plasma membranes of the sperm and oocyte have fused and that the head and tail of the sperm enter the oocyte, leaving the sperm’s plasma membrane attached to the oocyte’s plasma membrane. C, Scanning electron microscopy of an unfertilized human oocyte showing relatively few sperms attached to the zona pellucida. D, Scanning electron microscopy of a human oocyte showing penetration of the sperm (arrow) into the zona pellucida.
  60. Male Fertility
  61. Vasectomy
  62. Dispermy and Triploidy
  63. Viability of Gametes
  64. Fertilization
  65. Phases of Fertilization
  66. FIGURE 2-14 Illustrations of fertilization, the procession of events beginning when the sperm contacts the secondary oocyte’s plasma membrane, and ending with the intermingling of maternal and paternal chromosomes at metaphase of the first mitotic division of the zygote. A, Secondary oocyte surrounded by several sperms, two of which have penetrated the corona radiata. (Only 4 of the 23 chromosome pairs are shown.) B, The corona radiata is not shown, a sperm has entered the oocyte, and the second meiotic division has occurred, forming a mature oocyte. The nucleus of the oocyte is now the female pronucleus. C, The sperm head has enlarged to form the male pronucleus. This cell, now called an ootid, contains the male and female pronuclei. D, The pronuclei are fusing. E, The zygote has formed; it contains 46 chromosomes, the diploid number.
  67. Fertilization
  68. Preselection of Embryo’s Sex
  69. Assisted Reproductive Technologies
  70. In Vitro Fertilization and Embryo Transfer
  71. Cryopreservation of Embryos
  72. Intracytoplasmic Sperm Injection
  73. Assisted In Vivo Fertilization
  74. Surrogate Mothers
  75. Cleavage of Zygote
  76. FIGURE 2-15 In vitro fertilization (IVF) and embryo transfer procedures.
  77. FIGURE 2-16 Illustrations of cleavage of the zygote and formation of the blastocyst. A to D, Various stages of cleavage of the zygote. The period of the morula begins at the 12- to 16-cell stage and ends when the blastocyst forms. E and F, Sections of blastocysts. The zona pellucida has disappeared by the late blastocyst stage (5 days). The second polar bodies shown in A are small, nonfunctional cells. Cleavage of the zygote and formation of the morula occur as the dividing zygote passes along the uterine tube. Blastocyst formation occurs in the uterus. Although cleavage increases the number of blastomeres, note that each of the daughter cells is smaller than the parent cells. As a result, there is no increase in the size of the developing embryo until the zona pellucida degenerates. The blastocyst then enlarges considerably (F).
  78. Mosaicism
  79. Formation of Blastocyst
  80. FIGURE 2-17 A, Two-cell stage of a cleaving zygote developing in vitro. Observe that it is surrounded by many sperms. B, In vitro fertilization, two-cell stage human embryo. The zona pellucida has been removed. A small rounded polar body (pink) is still present on the surface of a blastomere (artificially colored, scanning electron microscopy, ×1000). C, Three-cell stage human embryo, in vitro fertilization (scanning electron microscopy, ×1300). D, Eight-cell stage human embryo, in vitro fertilization (scanning electron microscopy, ×1100). Note the rounded large blastomeres with several spermatozoa attached.
  81. FIGURE 2-18 Photomicrographs of sections of human blastocysts recovered from the uterine cavity (×600). A, At 4 days: the blastocystic cavity is just beginning to form and the zona pellucida is deficient over part of the blastocyst. B, At 4.5 days; the blastocystic cavity has enlarged and the embryoblast and trophoblast are clearly defined. The zona pellucida has disappeared.
  82. FIGURE 2-19 Attachment of the blastocyst to the endometrial epithelium during the early stages of implantation. A, At 6 days: the trophoblast is attached to the endometrial epithelium at the embryonic pole of the blastocyst. B, At 7 days: the syncytiotrophoblast has penetrated the epithelium and has started to invade the endometrial connective tissue. Note: Some students have difficulty interpreting illustrations such as these because in histologic studies, it is conventional to draw the endometrial epithelium upward, whereas in embryologic studies, the embryo is usually shown with its dorsal surface upward. Because the embryo implants on its future dorsal surface, it would appear upside down if the histologic convention were followed. In this book, the histologic convention is followed when the endometrium is the dominant consideration (e.g., Fig. 2-6C), and the embryologic convention is used when the embryo is the center of interest, as in the adjacent illustrations.
  83. Preimplantation Genetic Diagnosis
  84. Abnormal Embryos and Spontaneous Abortions
  85. Summary of First Week (Fig. 2-20)
  86. FIGURE 2-20 Summary of the ovarian cycle, fertilization, and human development during the first week. Stage 1 of development begins with fertilization in the uterine tube and ends when the zygote forms. Stage 2 (days 2 to 3) comprises the early stages of cleavage (from 2 to approximately 32 cells, the morula). Stage 3 (days 4 to 5) consists of the free (unattached) blastocyst. Stage 4 (days 5 to 6) is represented by the blastocyst attaching to the posterior wall of the uterus, the usual site of implantation. The blastocysts have been sectioned to show their internal structure.
  87. Clinically Oriented Problems
  88. References and Suggested Reading
  89. Chapter 3 Second Week of Human Development
  90. Completion of Implantation of Blastocyst
  91. FIGURE 3-1 Implantation of a blastocyst in the endometrium. The actual size of the conceptus is 0.1 mm, approximately the size of the period at the end of this sentence. A, Drawing of a section through a blastocyst partially embedded in the uterine endometrium (approximately 8 days). Note the slit-like amniotic cavity. B, Drawing of a section through a blastocyst of approximately 9 days implanted in the endometrium. Note the lacunae appearing in the syncytiotrophoblast.
  92. FIGURE 3-2 Embedded blastocysts. A, 10 days; B, 12 days. This stage of development is characterized by communication of the blood-filled lacunar networks. Note in B that coelomic spaces have appeared in the extraembryonic mesoderm, forming the beginning of the extraembryonic coelom (cavity).
  93. Formation of Amniotic Cavity, Embryonic Disc, and Umbilical Vesicle
  94. FIGURE 3-3 Photograph of the endometrial surface of the body of the uterus, showing the implantation site of the 12-day embryo shown in Figure 3-4. The implanted conceptus produces a small elevation (arrow) (×8).
  95. FIGURE 3-4 Embedded blastocyst. A, Section through the implantation site of a 12-day embryo described in Figure 3-3. The embryo is embedded superficially in the compact layer of the endometrium (×30). B, Higher magnification of the conceptus (embryo and associated membranes) and uterine endometrium surrounding it (×100). Lacunae containing maternal blood are visible in the syncytiotrophoblast.
  96. Development of Chorionic Sac
  97. FIGURE 3-5 Drawings of sections of implanted human embryos, based mainly on Hertig and colleagues (1956). Observe (1) the defect in the endometrial epithelium has disappeared; (2) a small secondary umbilical vesicle has formed; (3) a large cavity, the extraembryonic coelom, now surrounds the umbilical vesicle and amnion, except where the amnion is attached to the chorion by the connecting stalk; and (4) the extraembryonic coelom splits the extraembryonic mesoderm into two layers: extraembryonic somatic mesoderm lining the trophoblast and covering the amnion, and the extraembryonic splanchnic mesoderm around the umbilical vesicle. A, 13-day embryo, illustrating the decrease in relative size of the primary umbilical vesicle and the early appearance of primary chorionic villi. B, 14-day embryo, showing the newly formed secondary umbilical vesicle and the location of the prechordal plate in its roof. C, Detail of the prechordal plate outlined in B.
  98. FIGURE 3-6 Origin of embryonic tissues. The colors in the boxes are used in drawings of sections of conceptuses.
  99. FIGURE 3-7 Endovaginal sonogram (sagittal and axial) of an early chorionic (gestational) sac (5 weeks) (+). The mean chorionic sac diameter is calculated from the three orthogonal measurements (d1, d2, d3) and dividing by 3. The secondary umbilical vesicle (yolk sac) can also be seen.
  100. FIGURE 3-8 Photomicrographs of longitudinal sections of an embedded 14-day embryo. Note the large size of the extraembryonic coelom. A, Low-power view (×18). B, High-power view (×95). The embryo is represented by the bilaminar embryonic disc composed of epiblast and hypoblast.
  101. Implantation Sites of Blastocysts
  102. Extrauterine Implantations
  103. Summary of Implantation
  104. FIGURE 3-9 A, Frontal section of the uterus and left uterine tube, illustrating an ectopic pregnancy in the ampulla of the tube. B, Ectopic tubal pregnancy. Endovaginal axial sonogram of the uterine fundus and isthmic portion of the right uterine tube. The ring-like mass is a 4-week ectopic chorionic sac in the tube.
  105. FIGURE 3-10 Implantation sites of blastocysts. The usual site in the posterior wall of the body of the uterus is indicated by an X. The approximate order of frequency of ectopic implantations is indicated alphabetically (A, most common, H, least common). A to F, tubal pregnancies; G, abdominal pregnancy; H, ovarian pregnancy. Tubal pregnancies are the most common type of ectopic pregnancy. Although appropriately included with uterine pregnancy sites, a cervical pregnancy is often considered to be an ectopic pregnancy.
  106. FIGURE 3-11 Tubal pregnancy. The uterine tube has been surgically removed and sectioned to show the 5-week old embryo (10 mm crown-rump length CRL) within the opened chorionic sac (C). Note the fragments of the amnion (A) and the thin mucosal folds (M) of the uterine tube projecting into the lumen of the tube.
  107. Placenta Previa
  108. Spontaneous Abortion of Embryos and fetuses
  109. Inhibition of Implantation
  110. Summary of Second Week
  111. Clinically Oriented Problems
  112. Case 3–1
  113. Case 3–2
  114. Case 3–3
  115. Case 3–4
  116. Case 3–5
  117. References and Suggested Reading
  118. Chapter 4 Third Week of Human Development
  119. FIGURE 4-1 Ultrasonograph sonogram of a 3.5-week conceptus. Note the surrounding secondary umbilical vesicle (calipers) and the surrounding trophoblast (bright ring of tissue).
  120. Pregnancy Symptoms
  121. Gastrulation: Formation of Germ Layers
  122. Primitive Streak
  123. FIGURE 4-2 Illustrations of the formation of the trilaminar embryonic disc (days 15 to 16). The arrows indicate invagination and migration of mesenchymal cells from the primitive streak between the ectoderm and endoderm. C, E, and G, Dorsal views of the trilaminar embryonic disc early in the third week, exposed by removal of the amnion. A, B, D, F, and H, Transverse sections through the embryonic disc. The levels of the sections are indicated in C, E, and G. The prechordal plate, indicating the head region in Fig. 4-2C, is indicated by a light blue oval because this thickening of endoderm cannot be seen from the dorsal surface.
  124. FIGURE 4-3 A, Dorsal view of an embryo approximately 16 days old. B, Drawing of structures shown in A.
  125. FIGURE 4-4 A, Drawing of a dorsal view of a 16-day embryo. The amnion has been removed to expose the primitive node, primitive pit and primitive streak. B, Drawing of the cranial half of the embryonic disc. The trilaminar embryonic disc has been cut transversely to show the migration of mesenchymal cells from the primitive streak to form mesoblast that soon organizes to form the intraembryonic mesoderm. This illustration also shows that most of the embryonic endoderm also arises from the epiblast. Most of the hypoblastic cells are displaced to extraembryonic regions such as the wall of the umbilical vesicle.
  126. Fate of Primitive Streak
  127. FIGURE 4-5 Diagrammatic sketches of dorsal views of the embryonic disc showing how it lengthens and changes shape during the third week. The primitive streak lengthens by addition of cells at its caudal end, and the notochordal process lengthens by migration of cells from the primitive node. The notochordal process and adjacent mesoderm induce the overlying embryonic ectoderm to form the neural plate, the primordium of the CNS. Observe that as the notochordal process elongates, the primitive streak shortens. At the end of the third week, the notochordal process is transformed into the notochord.
  128. Sacrococcygeal Teratoma
  129. Notochordal Process and Notochord
  130. FIGURE 4-6 Female infant with a large sacrococcygeal teratoma that developed from remnants of the primitive streak. The tumor, a neoplasm made up of several different types of tissue, was surgically removed.
  131. Remnants of Notochordal Tissue
  132. Allantois
  133. FIGURE 4-7 Illustrations of developing notochordal process. The small sketch at the upper left is for orientation. A, Dorsal view of the embryonic disc (approximately 16 days) exposed by removal of the amnion. The notochordal process is shown as if it were visible through the embryonic ectoderm. B, C, and E, Median sections at the plane shown in A, illustrating successive stages in the development of the notochordal process and canal. The stages shown in C and E occur at approximately 18 days. D and F, Transverse sections through the embryonic disc at the levels shown in C and E.
  134. FIGURE 4-8 Illustrations of notochord development by transformation of the notochordal process. A, Dorsal view of the bilaminar embryonic disc at 18 days, exposed by removing the amnion. B, Three-dimensional median section of the embryo. C and E, Similar sections of slightly older embryos. D, F, and G, Transverse sections of the trilaminar embryonic disc at the levels shown in C and E.
  135. Allantoic Cysts
  136. Neurulation: Formation of Neural Tube
  137. Neural Plate and Neural Tube
  138. Neural Crest Formation
  139. FIGURE 4-9 Drawings of embryos at 19 to 21 days illustrating development of the somites and intraembryonic coelom. A, C, and E, Dorsal views of the embryo, exposed by removal of the amnion. B, D, and F, Transverse sections through the trilaminar embryonic disc at the levels shown. A, Presomite embryo of approximately 18 days. C, An embryo of approximately 20 days showing the first pair of somites. Part of the somatopleure on the right has been removed to show the coelomic spaces in the lateral mesoderm. E, A three-somite embryo (approximately 21 days) showing the horseshoe-shaped intraembryonic coelom, exposed on the right by removal of part of the somatopleure.
  140. FIGURE 4-10 Diagrammatic drawings transverse sections through progressively older embryos illustrating formation of the neural groove, neural folds, neural tube, and neural crest. A, Dorsal view of an embryo at approximately 21 days.
  141. Birth Defects Resulting from Abnormal Neurulation
  142. Development of Somites
  143. Development of Intraembryonic Coelom
  144. Early Development of Cardiovascular System
  145. Vasculogenesis and Angiogenesis
  146. Primordial Cardiovascular System
  147. FIGURE 4-11 Successive stages in the development of blood and blood vessels. A, Lateral view of the umbilical vesicle and part of the chorionic sac (approximately 18 days). B, Dorsal view of the embryo exposed by removing the amnion (approximately 20 days). C to F, Sections of blood islands showing progressive stages in the development of blood and blood vessels.
  148. Abnormal Growth of Trophoblast
  149. Development of Chorionic Villi
  150. FIGURE 4-12 Diagram of the primordial cardiovascular system in an embryo of approximately 21 days, viewed from the left side. Observe the transitory stage of the paired symmetrical vessels. Each heart tube continues dorsally into a dorsal aorta that passes caudally. Branches of the aortae are (1) umbilical arteries establishing connections with vessels in the chorion, (2) vitelline arteries to the umbilical vesicle, and (3) dorsal intersegmental arteries to the body of the embryo. Vessels on the umbilical vesicle form a vascular plexus that is connected to the heart tubes by vitelline veins. The cardinal veins return blood from the body of the embryo. The umbilical vein carries oxygenated blood and nutrients to f the chorion that provides nourishment to the embryo. The arteries carry poorly oxygenated blood and waste products to the chorionic villi for transfer to the mother’s blood.
  151. Summary of Third Week
  152. FIGURE 4-13 Endovaginal ultrasonogram of a 4-week embryo A, Secondary umbilical vesicle (calipers, 2 mm). B, Bright (echogenic) 4-week embryo (calipers, 2.4 mm) C, Cardiac activity of 116 beats per minute demonstrated with motion mode. The calipers are used to encompass two beats.
  153. FIGURE 4-14 Diagrams illustrating development of secondary chorionic villi into tertiary chorionic villi. Early formation of the placenta is also shown. A, Sagittal section of an embryo (approximately 16 days). B, Section of a secondary chorionic villus. C, Section of an implanted embryo (approximately 21 days). D, Section of a tertiary chorionic villus. The fetal blood in the capillaries is separated from the maternal blood surrounding the villus by the endothelium of the capillary, embryonic connective tissue, cytotrophoblast, and syncytiotrophoblast.
  154. Clinically Oriented Problems
  155. Case 4–1
  156. Case 4–2
  157. Case 4–3
  158. Case 4–4
  159. Case 4–5
  160. References and Suggested Reading
  161. Chapter 5 Fourth to Eighth Weeks of Human Development
  162. Phases of Embryonic Development
  163. Folding of Embryo
  164. Folding of Embryo in the Median Plane
  165. Head Fold
  166. Tail Fold
  167. Folding of Embryo in the Horizontal Plane
  168. Germ Layer Derivatives
  169. FIGURE 5-1 Drawings of folding of embryos during the fourth week. A1, Dorsal view of an embryo early in the fourth week. Three pairs of somites are visible. The continuity of the intraembryonic coelom and extraembryonic coelom is illustrated on the right side by removal of a part of the embryonic ectoderm and mesoderm. B1, C1, and D1, Lateral views of embryos at 22, 26, and 28 days, respectively. A2 to D2, Sagittal sections at the plane shown in A1. A3 to D3, Transverse sections at the levels indicated in A1 to D1.
  170. FIGURE 5-2 Folding of cranial end of embryo. A, Dorsal view of embryo at 21 days. B, Sagittal section of the cranial part of the embryo at the plane shown in A. Observe the ventral movement of the heart. C, Sagittal section of an embryo at 26 days. Note that the septum transversum, primordial heart, pericardial coelom, and oropharyngeal membrane have moved onto the ventral surface of the embryo. Observe also that part of the umbilical vesicle is incorporated into the embryo as the foregut.
  171. Control of Embryonic Development
  172. FIGURE 5-3 Drawings of the effect of the head fold on the intraembryonic coelom. A, Lateral view of an embryo (24 to 25 days) during folding, showing the large forebrain, ventral position of the heart, and communication between the intraembryonic and extraembryonic parts of the coelom. B, Schematic drawing of an embryo (26 to 27 days) after folding, showing the pericardial cavity ventrally, the pericardioperitoneal canals running dorsally on each side of the foregut, and the intraembryonic coelom in communication with the extraembryonic coelom.
  173. FIGURE 5-4 Folding of caudal end of the embryo. A, Sagittal section of caudal part of the embryo at the beginning of the fourth week. B, Similar section at the end of the fourth week. Note that part of the umbilical vesicle is incorporated into the embryo as the hindgut and that the terminal part of the hindgut has dilated to form the cloaca. Observe also the change in position of the primitive streak, allantois, cloacal membrane, and connecting stalk.
  174. Highlights of Fourth to Eighth Weeks
  175. Fourth Week
  176. FIGURE 5-5 Schematic drawing of derivatives of the three germ layers: ectoderm, endoderm, and mesoderm. Cells from these layers contribute to the formation of different tissues and organs; for instance, the endoderm forms the epithelial lining of the gastrointestinal tract and the mesoderm gives rise to connective tissues and muscles.
  177. Fifth Week
  178. Sixth Week
  179. Table 5-1 Criteria for Estimating Developmental Stages in Human Embryos
  180. FIGURE 5-6 A, Dorsal view of a five-somite embryo at Carnegie stage 10, approximately 22 days. Observe the neural folds and deep neural groove. The neural folds in the cranial region have thickened to form the primordium of the brain. B, Drawing of the structures shown in A. Most of the amniotic and chorionic sacs have been cut away to expose the embryo. C, Dorsal view of an older eight-somite embryo at Carnegie stage 10. The neural tube is in open communication with the amniotic cavity at the cranial and caudal ends through the rostral and caudal neuropores, respectively. D, Diagram of the structures shown in C. The neural folds have fused opposite the somites to form the neural tube (primordium of spinal cord in this region).
  181. FIGURE 5-7 A, Dorsal view of a 13-somite embryo at Carnegie stage 11, approximately 24 days. The rostral neuropore is closing, but the caudal neuropore is wide open. B, Illustration of the structures shown in A. The embryo is lightly curved because of folding at the cranial and caudal ends.
  182. Seventh Week
  183. FIGURE 5-8 A, Lateral view of a 27-somite embryo at Carnegie stage 12, approximately 26 days. The embryo is curved, especially its tail-like caudal eminence. Observe the lens placode (primordium of lens of eye) and the otic pit indicating early development of internal ear. B, Illustration of the structures shown in A. The rostral neuropore is closed and three pairs of pharyngeal arches are present.
  184. FIGURE 5-9 A, Lateral view of an embryo at Carnegie stage 13, approximately 28 days. The primordial heart is large, and its division into a primordial atrium and ventricle is visible. The rostral and caudal neuropores are closed. B, Drawing indicating the structures shown in A. The embryo has a characteristic C-shaped curvature, four pharyngeal arches, and upper and lower limb buds.
  185. FIGURE 5-10 A, Drawing of an embryo at Carnegie stage 13, approximately 28 days. B, Photomicrograph of a section of the embryo at the level shown in A. Observe the hindbrain and otic vesicle (primordium of internal ear). C, Drawing of same embryo showing the level of the section in D. Observe the primordial pharynx and pharyngeal arches.
  186. FIGURE 5-11 A, Drawing of an embryo at Carnegie stage 13, approximately 28 days. B, Photomicrograph of a section of the embryo at the level shown in A. Observe the parts of the primordial heart. C, Drawing of the same embryo showing the level of section in D. Observe the primordial heart and stomach.
  187. FIGURE 5-12 A, Scanning electron micrograph of the craniofacial region of a human embryo of approximately 32 days (Carnegie stage 14, 6.8 mm). Three pairs of pharyngeal arches are present. The maxillary and mandibular prominences of the first arch are clearly delineated. Observe the large mouth located between the maxillary prominences and the fused mandibular prominences. B, Drawing of the scanning electron micrograph illustrating the structures shown in A.
  188. FIGURE 5-13 A, Lateral view of an embryo at Carnegie stage 14, approximately 32 days. The second pharyngeal arch has overgrown the third arch, forming the cervical sinus. The mesonephric ridge indicates the site of the mesonephric kidney, an interim kidney (see Chapter 12). B, Illustration of the structures shown in A. The upper limb buds are paddle shaped and the lower limb buds are flipper-like.
  189. FIGURE 5-14 A, Lateral view of an embryo at Carnegie stage 17, approximately 42 days. Digital rays are visible in the hand plate, indicating the future site of the digits. B, Drawing illustrating the structures shown in A. The eye, auricular hillocks, and external acoustic meatus are now obvious.
  190. FIGURE 5-15 A, Lateral view of an embryo at Carnegie stage 19, about 48 days. The auricle and external acoustic meatus are now clearly visible. Note the relatively low position of the ear at this stage. Digital rays are now visible in the footplate. The prominence of the abdomen is caused mainly by the large size of the liver. B, Drawing indicating the structures shown in A. Observe the large hand and the notches between the digital rays, which clearly indicate the developing digits or fingers.
  191. FIGURE 5-16 A, Lateral view of an embryo at Carnegie stage 21, approximately 52 days. Note that the feet are fan-shaped. The scalp vascular plexus now forms a characteristic band across the head. The nose is stubby and the eye is heavily pigmented. B, Illustration of the structures shown in A. The fingers are separated and the toes are beginning to separate. C, A Carnegie stage 20 human embryo, approximately 50 days after ovulation, imaged with optical microscopy (left) and magnetic resonance microscopy (right). The three-dimensional data set from magnetic resonance microscopy has been edited to reveal anatomic detail from a mid-sagittal plane.
  192. Eighth Week
  193. FIGURE 5-17 A, Lateral view of an embryo at Carnegie stage 23, approximately 56 days. The embryo has a distinct human appearance. B, Illustration of the structures shown in A. C, A Carnegie stage 23 embryo, approximately 56 days after ovulation, imaged with optical microscopy (left) and magnetic resonance microscopy (right).
  194. FIGURE 5-18 Lateral view of an embryo and its chorionic sac at Carnegie stage 23, approximately 56 days. Observe the human appearance of the embryo.
  195. FIGURE 5-19 Transvaginal sonogram of a 7-week embryo (calipers, CRL 10 mm) surrounded by the amniotic membrane within the chorionic cavity (dark region).
  196. Estimation of Gestational and Embryonic Age
  197. Estimation of Embryonic Age
  198. Ultrasound Examination of Embryos
  199. Summary of Fourth to Eighth Weeks
  200. FIGURE 5-20 Illustrations of methods used to measure the length of embryos. A, Greatest length (GL). B, C, and D, Crown-rump length (CRL). D, Photograph of an 8-week-old embryo
  201. Clinically Oriented Problems
  202. Case 5–1
  203. Case 5–2
  204. Case 5–3
  205. Case 5–4
  206. Case 5–5
  207. References and Suggested Reading
  208. Chapter 6 Ninth Week to Birth: The Fetal Period
  209. Table 6-1 Criteria for Estimating Fertilization Age during the Fetal Period
  210. Viability of Fetuses
  211. Estimation of Fetal Age
  212. Table 6-2 Comparison of Gestational Time Units and Date of Birth
  213. Trimesters of Pregnancy
  214. Measurements and Characteristics of Fetuses
  215. Highlights of Fetal Period
  216. Nine to Twelve Weeks
  217. FIGURE 6-1 Ultrasound image of 9-week fetus (11 weeks gestational age). Note the amnion, amniotic cavity (A), and chorionic cavity (C). CRL 4.2 cm (calipers).
  218. FIGURE 6-2 A 9-week fetus in the amniotic sac exposed by removal from the chorionic sac. A, Actual size. The remnant of the umbilical vesicle is indicated by an arrow. B, Enlarged photograph of the fetus (x2). Note the following features: large head, fused eyelids, cartilaginous ribs, and intestines in umbilical cord (arrow).
  219. Thirteen to Sixteen Weeks
  220. FIGURE 6-3 An 11-week fetus (x1.5). Note its relatively large head and that the intestines are no longer in the umbilical cord.
  221. FIGURE 6-4 Diagram, drawn to scale, illustrating the changes in the size of the human fetus.
  222. FIGURE 6-5 Enlarged photograph of the head and superior part of the trunk of a 13-week fetus.
  223. Seventeen to Twenty Weeks
  224. FIGURE 6-6 A, A 17-week fetus. Because there is little subcutaneous tissue and the skin is thin, the blood vessels of the scalp are visible. Fetuses at this age are unable to survive if born prematurely, mainly because their respiratory systems are immature. B, A frontal view of a 17-week fetus. Note that the eyes are closed at this stage.
  225. Twenty-One to Twenty-Five Weeks
  226. Twenty-Six to Twenty-Nine Weeks
  227. FIGURE 6-7 A 25-week-old normal female newborn weighing 725 g.
  228. FIGURE 6-8 Magnetic resonance images (MRIs) of normal fetuses. A, At 18 weeks (20-week gestational age). B, At 26 weeks. C, At 28 weeks.
  229. Thirty to Thirty-Four Weeks
  230. Thirty-Five to Thirty-Eight Weeks
  231. FIGURE 6-9 Healthy newborns. A, At 34 weeks (36-week gestational age). B, At 38 weeks (40-week gestational age).
  232. FIGURE 6-10 Ultrasound scan of the foot of a fetus at 19 weeks.
  233. FIGURE 6-11 Graph showing the rate of fetal growth during the last trimester (3 months). Average refers to babies born in the United States. After 36 weeks, the growth rate deviates from the straight line. The decline, particularly after full term (38 weeks), probably reflects inadequate fetal nutrition caused by placental changes.
  234. Low Birth Weight
  235. Expected Date of Delivery
  236. Postmaturity Syndrome
  237. Factors Influencing Fetal Growth
  238. Cigarette Smoking
  239. Multiple Pregnancy
  240. Alcohol and Illicit Drugs
  241. Impaired Uteroplacental and Fetoplacental Blood Flow
  242. Genetic Factors and Growth Retardation
  243. Procedures for Assessing Fetal Status
  244. Ultrasonography
  245. Diagnostic Amniocentesis
  246. FIGURE 6-12 A, Three-dimensional ultrasound (sonogram) of a 28-week fetus showing the face. The surface features are clearly recognizable. B, Photograph of the newborn infant (from A) 3 hours after birth.
  247. FIGURE 6-13 A, Illustration of amniocentesis. A needle is inserted through the lower abdominal and uterine walls into the amniotic cavity. A syringe is attached and amniotic fluid is withdrawn for diagnostic purposes. B, Drawing illustrating chorionic villus sampling. Two sampling approaches are illustrated: through the maternal anterior abdominal wall with a needle and through the vagina and cervical canal using a malleable catheter. A speculum is an instrument for exposing the vagina.
  248. Diagnostic Value of Amniocentesis
  249. Alpha-Fetoprotein Assay
  250. Alpha-Fetoprotein and Fetal Anomalies
  251. Spectrophotometric Studies
  252. Chorionic Villus Sampling
  253. Diagnostic Value of Chorionic Villus Sampling
  254. Sex Chromatin Patterns
  255. FIGURE 6-14 Oral epithelial nuclei stained with cresyl echt violet (A, B, and C) and quinacrine mustard (D) (x2000). A, From normal male. No sex chromatin is visible (chromatin negative). B, From normal female. The arrow indicates a typical mass of sex chromatin (chromatin positive). C, From female with 47, XXX trisomy. The arrows indicate two masses of sex chromatin. D, From normal male. The arrow indicates a mass of Y chromatin as an intensely fluorescent body.
  256. Cell Cultures and Chromosomal Analysis
  257. Fetal Transfusion
  258. Fetoscopy
  259. Percutaneous Umbilical Cord Blood Sampling
  260. Magnetic Resonance Imaging
  261. Fetal Monitoring
  262. FIGURE 6-15 Sagittal magnetic resonance image of the pelvis of a pregnant woman. The fetus is in the breech presentation. Note the brain, eyes, and liver.
  263. Summary of Fetal Period
  264. FIGURE 6-16 Fetus at 21 weeks undergoing bilateral ureterostomies, the establishment of openings of the ureters into the bladder.
  265. Clinically Oriented Problems
  266. Case 6–1
  267. Case 6–2
  268. Case 6–3
  269. Case 6–4
  270. Case 6–5
  271. Case 6–6
  272. References and Suggested Reading
  273. Chapter 7 Placenta and Fetal Membranes
  274. Placenta
  275. Decidua
  276. Development of Placenta
  277. Ultrasonography of Chorionic Sac
  278. FIGURE 7-1 Development of the placenta and fetal membranes. A, Frontal section of the uterus showing elevation of the decidua capsularis by the expanding chorionic sac of a 4-week embryo implanted in the endometrium on the posterior wall (*). B, Enlarged drawing of the implantation site. The chorionic villi were exposed by cutting an opening in the decidua capsularis. C to F, Sagittal sections of the gravid or pregnant uterus from weeks 5 to 22 showing the changing relations of the fetal membranes to the decidua. In F, the amnion and chorion are fused with each other and the decidua parietalis, thereby obliterating the uterine cavity. Note in D to F that the chorionic villi persist only where the chorion is associated with the decidua basalis.
  279. FIGURE 7-2 A, Lateral view of a spontaneously aborted embryo at Carnegie stage 14, approximately 32 days. The chorionic and amniotic sacs have been opened to show the embryo. Note the large size of the umbilical vesicle at this stage. B, The sketch shows the actual size of the embryo and its membranes.
  280. FIGURE 7-3 Spontaneously aborted human chorionic sacs. A, At 21 days. The entire sac is covered with chorionic villi (x4). B, At 8 weeks. Actual size. Some of the chorionic villi have degenerated forming the smooth chorion.
  281. Placental Circulation
  282. FIGURE 7-4 Drawing of a sagittal section of a gravid uterus at 4 weeks shows the relation of the fetal membranes to each other and to the decidua and embryo. The amnion and smooth chorion have been cut and reflected to show their relationship to each other and the decidua parietalis.
  283. Fetal Placental Circulation
  284. Maternal Placental Circulation
  285. Placental Membrane
  286. FIGURE 7-5 Schematic drawing of a transverse section through a full-term placenta, showing (1) the relation of the villous chorion (fetal part of placenta) to the decidua basalis (maternal part of placenta), (2) the fetal placental circulation, and (3) the maternal placental circulation. Note that the umbilical arteries carry poorly oxygenated fetal blood (shown in blue) to the placenta and that the umbilical vein carries oxygenated blood (shown in red) to the fetus. Note that the cotyledons are separated from each other by placental septa, projections of the decidua basalis. Each cotyledon consists of two or more main stem villi and many branch villi. In this drawing, only one stem villus is shown in each cotyledon, but the stumps of those that have been removed are indicated.
  287. FIGURE 7-6 A, Drawing of a stem chorionic villus showing its arteriocapillary-venous system. The arteries carry poorly oxygenated fetal blood and waste products from the fetus, whereas the vein carries oxygenated blood and nutrients to the fetus. B and C, Drawings of sections through a branch villus at 10 weeks and full term, respectively. The placental membrane, composed of extrafetal tissues, separates the maternal blood in the intervillous space from the fetal blood in the capillaries in the villi. Note that the placental membrane becomes very thin at full term. Hofbauer cells are thought to be phagocytic cells.
  288. Functions of Placenta
  289. Placental Metabolism
  290. Placental Transfer
  291. FIGURE 7-7 Diagrammatic illustration of transfer across the placental membrane (barrier). The extrafetal tissues, across which transport of substances between the mother and fetus occurs, collectively constitute the placental membrane. Inset, Light micrograph of chorionic villus showing a fetal capillary and the placental membrane (arrow).
  292. Other Placental Transport Mechanisms
  293. Transfer of Gases
  294. Nutritional Substances
  295. Hormones
  296. Electrolytes
  297. Maternal Antibodies and Proteins
  298. Hemolytic Disease of the Newborn
  299. Waste Products
  300. Drugs and Drug Metabolites
  301. Infectious Agents
  302. Placental Endocrine Synthesis and Secretion
  303. The Placenta as an Allograft*
  304. Placenta as an Invasive Tumor-like Structure
  305. Preeclampsia
  306. Uterine Growth during Pregnancy
  307. Parturition
  308. FIGURE 7-8 Drawings of median sections of a woman’s body. A, Not pregnant. B, Twenty weeks pregnant. C, Thirty weeks pregnant. Note that as the conceptus enlarges, the uterus increases in size to accommodate the rapidly growing fetus. By 20 weeks, the uterus and fetus reach the level of the umbilicus, and by 30 weeks, they reach the epigastric region. The mother’s abdominal viscera are displaced and compressed, and the skin and muscles of her anterior abdominal wall are stretched.
  309. FIGURE 7-9 Drawings illustrating parturition (childbirth). A and B, The cervix is dilating during the first stage of labor. C to E, The fetus is passing through the cervix and vagina during the second stage of labor. F and G, As the uterus contracts during the third stage of labor, the placenta folds and pulls away from the uterine wall. Separation of the placenta results in bleeding and formation of a large hematoma (mass of blood). Pressure on the abdomen facilitates placental separation. H, The placenta is expelled and the uterus contracts.
  310. FIGURE 7-10 Delivery of the baby’s head during the second stage of labor is shown. A, The crown of the head distends the mother’s perineum. B, The perineum slips over the head and face. C, The head is delivered: subsequently, the body of the fetus is expelled.
  311. Placenta and Fetal Membranes after Birth
  312. Gestational Choriocarcinoma
  313. Maternal Surface of Placenta
  314. Fetal Surface of Placenta
  315. FIGURE 7-11 Placentas and fetal membranes after birth, approximately one third actual size. A, Maternal surface showing cotyledons and the grooves around them. Each cotyledon consists of a number of main stem villi with their many branch villi. The grooves were occupied by the placental septa when the maternal and fetal parts of the placenta were together (see Fig. 7–5). B, Fetal surface showing blood vessels running in the chorionic plate deep to the amnion and converging to form the umbilical vessels at the attachment of the umbilical cord. Placentas and fetal membranes after birth, approximately one third of actual size. C, The amnion and smooth chorion are arranged to show that they are fused and continuous with the margins of the placenta. D, Placenta with a marginal attachment of the cord, often called a battledore placenta because of its resemblance to the bat used in the medieval game of battledore and shuttlecock.
  316. FIGURE 7-12 A full-term placenta and an accessory placenta (arrow). The accessory placenta developed from a patch of chorionic villi that persisted a short distance from the main placenta.
  317. FIGURE 7-13 Sagittal magnetic resonance image of the pelvis of a pregnant woman. The vertebral column and pelvis of the mother are visible, as are the fetal brain, limbs and placenta (P).
  318. Placental Abnormalities
  319. Umbilical Cord
  320. FIGURE 7-14 Placental abnormalities. In placenta accreta, there is abnormal adherence of the placenta to the myometrium. In placenta percreta, the placenta has penetrated the full thickness of the myometrium. In this example of placenta previa, the placenta overlies the internal os of the uterus and blocks the cervical canal.
  321. Umbilical Artery Doppler Velocimetry
  322. Absence of an Umbilical Artery
  323. Amnion and Amniotic Fluid
  324. Amniotic Fluid
  325. FIGURE 7-15 A placenta with a velamentous insertion of the umbilical cord. The cord is attached to the membranes (amnion and chorion), not to the placenta. The umbilical vessels leave the cord and run between the amnion and chorion before spreading over the placenta. The vessels are easily torn in this location, especially when they cross over the inferior uterine segment; the latter condition is known as vasa previa. If the vessels rupture before birth, the fetus loses blood and could be near exsanguination when born.
  326. FIGURE 7-16 Photograph of an umbilical cord showing a true knot. Such a knot will cause severe anoxia (decreased oxygen in the fetal tissues and organs).
  327. FIGURE 7-17 Doppler velocimetry of the umbilical cord. The arterial waveform (top) illustrates pulsatile forward flow, with high peaks and low velocities during diastole. This combination suggests high resistance in the placenta to placental blood flow. Because this index changes over gestation, it is important to know that the pregnancy was 18 weeks’ gestation. For this period, the flow pattern is normal. The nonpulsatile flow in the opposite, negative direction represents venous return from the placenta. Both waveforms are normal for this gestational age.
  328. FIGURE 7-18 Transverse section of an umbilical cord. Observe that the cord is covered by epithelium derived from the enveloping amnion. It has a core of mucous connective tissue (Wharton jelly). Observe also that the cord has one umbilical artery and one vein; usually there are two umbilical arteries.
  329. FIGURE 7-19 A, 12-week fetus within its amniotic sac. The fetus and its membranes aborted spontaneously. It was removed from its chorionic sac with its amniotic sac intact. Actual size. B, Note that the umbilical cord is looped around the left ankle of the fetus. Coiling of the cord around parts of the fetus affects development when the coils are so tight that the circulation to the parts is affected.
  330. FIGURE 7-20 Illustrations showing how the amnion enlarges, obliterates the chorionic cavity, and envelops the umbilical cord. Observe that part of the umbilical vesicle is incorporated into the embryo as the primordial gut. Formation of the fetal part of the placenta and degeneration of chorionic villi are also shown. A, At 3 weeks. B, At 4 weeks. C, At 10 weeks. D, At 20 weeks.
  331. Circulation of Amniotic Fluid
  332. Disorders of Amniotic Fluid Volume
  333. Composition of Amniotic Fluid
  334. Significance of Amniotic Fluid
  335. FIGURE 7-21 A fetus with the amniotic band syndrome showing amniotic bands constricting the left arm.
  336. Premature Rupture of Fetal Membranes
  337. Umbilical Vesicle
  338. Significance of Umbilical Vesicle
  339. Fate of Umbilical Vesicle
  340. Allantois
  341. FIGURE 7-22 Illustrations of the development and usual fate of the allantois. A, A 3-week embryo. B, A 9-week fetus. C, A 3-month male fetus. D, Adult female. The nonfunctional allantois forms the urachus in the fetus and the median umbilical ligament in the adult.
  342. Allantoic Cysts
  343. Multiple Pregnancies
  344. Twins and Fetal Membranes
  345. Table 7-1 Frequency of Types of Placentas and Fetal Membranes in Monozygotic (MZ) and Dizygotic (DZ) Twins
  346. FIGURE 7-23 Sonogram of the umbilical cord of a 7-week fetus exhibiting an allantoic cyst (at calipers).
  347. Dizygotic Twins
  348. Anastomosis of Placental Blood Vessels
  349. Monozygotic Twins
  350. FIGURE 7-24 Diagrams illustrating how dizygotic twins develop from two zygotes. The relationships of the fetal membranes and placentas are shown for instances in which the blastocysts implant separately (A) and the blastocysts implant close together (B). In both cases, there are two amnions and two chorions. The placentas are usually fused when they implant close together.
  351. FIGURE 7-25 Diagrams illustrating how approximately 65% of monozygotic twins develop from one zygote by division of the embryoblast of the blastocyst. These twins always have separate amnions, a single chorionic sac, and a common placenta. If there is anastomosis of the placental vessels, one twin may receive most of the nutrition from the placenta. Inset, monozygotic twins, 17 weeks’ gestation.
  352. FIGURE 7-26 A, Three-dimensional ultrasound scan of a 6-week monochorionic diamniotic discordant twins. The normal twin (right) is seen surrounded by the amniotic membrane and adjacent to the umbilical vesicle. The arms and legs can also be seen. The smaller fetus is also visible (above left). B, Monozygotic, monochorionic, diamniotic twins showing a wide discrepancy in size resulting from an uncompensated arteriovenous anastomosis of placental vessels. Blood was shunted from the smaller twin to the larger one, producing the twin transfusion syndrome.
  353. FIGURE 7-27 Diagrams illustrating how approximately 35% of monozygotic twins develop from one zygote. Separation of the blastomeres may occur anywhere from the two-cell stage to the morula stage, producing two identical blastocysts. Each embryo subsequently develops its own amniotic and chorionic sacs. The placentas may be separate or fused. In 25% of cases, there is a single placenta resulting from secondary fusion, and in 10% of cases, there are two placentas. In the latter cases, examination of the placenta would suggest that they were dizygotic twins. This explains why some monozygotic twins are wrongly stated to be dizygotic twins at birth.
  354. Twin Transfusion Syndrome
  355. Establishing the Zygosity of Twins
  356. Early Death of a Twin
  357. Conjoined Monozygotic Twins
  358. Superfecundation
  359. Other Types of Multiple Births
  360. FIGURE 7-28 Diagrams illustrating how some monozygotic twins develop. This method of development is very uncommon. Division of the embryonic disc results in two embryos within one amniotic sac. A, Complete division of the embryonic disc gives rise to twins. Such twins rarely survive because their umbilical cords are often so entangled that interruption of the blood supply to the fetuses occurs. B and C, Incomplete division of the disc results in various types of conjoined twins.
  361. FIGURE 7-29 Serial ultrasound scans of a dichorionic pregnancy. A, At 3 weeks gestation. B, At 7 weeks gestation.
  362. FIGURE 7-30 A, Newborn monozygotic conjoined twins showing union in the thoracic regions (thoracopagus). B, The twins approximately 4 years after separation.
  363. FIGURE 7-31 Parasitic twins, anterior view. Note normal tone and posture of fully developed host twin with meconium staining, exstrophy of the bladder in both host and parasitic twins, exposed small bowel in parasitic twin, and fully formed right lower limb with normal tone and flexion in the parasitic twin.
  364. FIGURE 7-32 Dicephalic (two heads) conjoined twins, alizarin stained, showing bone (red) and cartilage (blue). Note the two clavicles supporting the midline upper limb, fused thoracic cage, and parallel vertebral columns.
  365. Summary of Placenta and Fetal Membranes
  366. Clinically Oriented Problems
  367. Case 7–1
  368. Case 7–2
  369. Case 7–3
  370. Case 7–4
  371. Case 7–5
  372. Case 7–6
  373. References and Suggested Reading
  374. Chapter 8 Body Cavities and Diaphragm
  375. Embryonic Body Cavity
  376. FIGURE 8-1 A, Drawing of a dorsal view of a 22-day embryo showing the outline of the horseshoe-shaped intraembryonic coelom. The amnion has been removed and the coelom is shown as if the embryo were translucent. The continuity of the intraembryonic coelom, as well as the communication of its right and left limbs with the extraembryonic coelom, is indicated by arrows. B, Transverse section through the embryo at the level shown in A.
  377. FIGURE 8-2 Illustrations of embryonic folding and its effects on the intraembryonic coelom and other structures. A, Lateral view of an embryo (approximately 26 days). B, Schematic sagittal section of this embryo showing the head and tail folds. C, Transverse section at the level shown in A, indicating how fusion of the lateral folds gives the embryo a cylindrical form. D, Lateral view of an embryo (approximately 28 days). E, Schematic sagittal section of this embryo showing the reduced communication between the intraembryonic and extraembryonic coeloms (double-headed arrow). F, Transverse section as indicated in D, illustrating formation of the ventral body wall and disappearance of the ventral mesentery. The arrows indicate the junction of the somatic and splanchnic layers of mesoderm. The somatic mesoderm will become the parietal peritoneum lining the abdominal wall, and the splanchnic mesoderm will become the visceral peritoneum covering the organs (e.g., the stomach).
  378. FIGURE 8-3 Illustrations of the mesenteries and body cavities at the beginning of the fifth week. A, Schematic sagittal section. Note that the dorsal mesentery serves as a pathway for the arteries supplying the developing gut. Nerves and lymphatics also pass between the layers of this mesentery. B to E, Transverse sections through the embryo at the levels indicated in A. The ventral mesentery disappears, except in the region of the terminal esophagus, stomach, and first part of the duodenum. Note that the right and left parts of the peritoneal cavity, separate in C, are continuous in E.
  379. FIGURE 8-4 Schematic drawings of an embryo (approximately 24 days). A, The lateral wall of the pericardial cavity has been removed to show the primordial heart. B, Transverse section of the embryo illustrating the relationship of the pericardioperitoneal canals to the septum transversum (primordium of central tendon of diaphragm) and the foregut. C, Lateral view of the embryo with the heart removed. The embryo has also been sectioned transversely to show the continuity of the intraembryonic and extraembryonic coeloms (arrow). D, Sketch showing the pericardioperitoneal canals arising from the dorsal wall of the pericardial cavity and passing on each side of the foregut to join the peritoneal cavity. The arrow shows the communication of the extraembryonic coelom with the intraembryonic coelom and the continuity of the intraembryonic coelom at this stage.
  380. Mesenteries
  381. Division of Embryonic Body Cavity
  382. FIGURE 8-5 Drawings of transverse sections through embryos cranial to the septum transversum, illustrating successive stages in the separation of the pleural cavities from the pericardial cavity. Growth and development of the lungs, expansion of the pleural cavities, and formation of the fibrous pericardium are also shown. A, At 5 weeks. The arrows indicate the communications between the pericardioperitoneal canals and the pericardial cavity. B, At 6 weeks. The arrows indicate development of the pleural cavities as they expand into the body wall. C, At 7 weeks. Expansion of the pleural cavities ventrally around the heart is shown. The pleuropericardial membranes are now fused in the median plane with each other and with the mesoderm ventral to the esophagus. D, At 8 weeks. Continued expansion of the lungs and pleural cavities and formation of the fibrous pericardium and thoracic wall are illustrated.
  383. Congenital Pericardial Defects
  384. Pleuropericardial Membranes
  385. Pleuroperitoneal Membranes
  386. FIGURE 8-6 A, The primordial body cavities are viewed from the left side after removal of the lateral body wall. B, Photograph of a 5-week-old embryo showing the developing septum transversum (arrow), heart tube (H), and liver (L). C, Transverse section through the embryo at the level shown in A.
  387. FIGURE 8-7 Illustrations of the development of the diaphragm. A, Lateral view of an embryo at the end of the fifth week (actual size) indicating the level of sections in B to D. B, Transverse section showing the unfused pleuroperitoneal membranes. C, Similar section at the end of the sixth week after fusion of the pleuroperitoneal membranes with the other two diaphragmatic components. D, Transverse section of a 12-week fetus after ingrowth of the fourth diaphragmatic component from the body wall. E, Inferior view of the diaphragm of a neonate indicating the embryologic origin of its components.
  388. Development of the Diaphragm
  389. Septum Transversum
  390. Pleuroperitoneal Membranes
  391. Dorsal Mesentery of the Esophagus
  392. Muscular Ingrowth from the Lateral Body Walls
  393. FIGURE 8-8 Illustrations of extension of the pleural cavities into the body walls to form peripheral parts of the diaphragm, the costodiaphragmatic recesses, and the establishment of the characteristic dome-shaped configuration of the diaphragm. Note that body wall tissue is added peripherally to the diaphragm as the lungs and pleural cavities enlarge.
  394. Positional Changes and Innervation of the Diaphragm
  395. Posterolateral Defect of Diaphragm
  396. Eventration of Diaphragm
  397. Gastroschisis and Congenital Epigastric Hernia
  398. FIGURE 8-9 A, A “window” has been drawn on the thorax and abdomen to show the herniation of the intestine into the thorax through a posterolateral defect in the left side of the diaphragm. Note that the left lung is compressed and hypoplastic. B, Drawing of a diaphragm with a large posterolateral defect on the left side due to abnormal formation and/or fusion of the pleuroperitoneal membrane on the left side with the mesoesophagus and septum transversum. C and D, Eventration of the diaphragm resulting from defective muscular development of the diaphragm. The abdominal viscera are displaced into the thorax within a pouch of diaphragmatic tissue.
  399. FIGURE 8-10 Coronal magnetic resonance image of a fetus with right-sided congenital diaphragmatic hernia. Note the liver (L) and loops of small intestine (arrowheads) in the thoracic cavity. There are ascites (*)—accumulation of serous fluid in the peritoneal cavity—extending into the thoracic cavity, and skin thickening (arrows).
  400. Congenital Hiatal Hernia
  401. Retrosternal (Parasternal) Hernia
  402. FIGURE 8-11 Diaphragmatic hernia on the left side of a fetus, showing herniation of liver (A), stomach, and bowel (B), underneath the liver into left thoracic cavity. Note the pulmonary hypoplasia visible after liver removal (female fetus at 19 to 20 weeks). C, Diaphragmatic hernia (posterolateral defect). Chest radiograph of a neonate showing herniation of intestinal loops (I) into the left side of the thorax. Note that the heart (H) is displaced to the right side and that the stomach (S) is on the left side of the upper abdominal cavity.
  403. Accessory Diaphragm
  404. Summary of Development of the Body Cavities and Diaphragm
  405. Clinically Oriented Problems
  406. Case 8–1
  407. Case 8–2
  408. Case 8–3
  409. Case 8–4
  410. References and Suggested Reading
  411. Chapter 9 Pharyngeal Apparatus, Face, and Neck
  412. Pharyngeal Arches
  413. FIGURE 9-1 Illustrations of the human pharyngeal apparatus. A, Dorsal view of the upper part of a 23-day embryo. B to D, Lateral views showing later development of the pharyngeal arches. E to G, Ventral or facial views illustrating the relationship of the first pharyngeal arch to the stomodeum. H, Horizontal section through the cranial region of an embryo. I, Similar section illustrating the pharyngeal arch components and the floor of the primordial pharynx. J, Sagittal section of the cranial region of an embryo, illustrating the openings of the pharyngeal pouches in the lateral wall of the primordial pharynx.
  414. Pharyngeal Arch Components
  415. FIGURE 9-2 Photograph of a stage 13, 4-1/2-week human embryo.
  416. Fate of Pharyngeal Arches
  417. Derivatives of Pharyngeal Arch Cartilages
  418. Derivatives of Pharyngeal Arch Muscles
  419. Derivatives of Pharyngeal Arch Nerves
  420. Pharyngeal Pouches
  421. FIGURE 9-3 A, Drawing of the head, neck, and thoracic regions of a human embryo (approximately 28 days), illustrating the pharyngeal apparatus. Inset, Photograph of a human embryo approximately the same age as A. B, Schematic drawing showing the pharyngeal pouches and pharyngeal arch arteries. C, Horizontal section through the embryo showing the floor of the primordial pharynx and illustrating the germ layer of origin of the pharyngeal arch components.
  422. FIGURE 9-4 A, Lateral view of the head, neck, and thoracic regions of an embryo (approximately 32 days), showing the pharyngeal arches and cervical sinus. B, Diagrammatic section through the embryo at the level shown in A, illustrating the growth of the second arch over the third and fourth arches. C, An embryo of approximately 33 days. D, Section of the embryo at the level shown in C, illustrating the early closure of the cervical sinus. E, An embryo of approximately 41 days. F, Section of the embryo at the level indicated in E, showing the transitory cystic remnant of the cervical sinus. G, Drawing of a 20-week fetus illustrating the area of the face derived from the first pair of pharyngeal arches.
  423. FIGURE 9-5 A, Schematic lateral view of the head, neck, and thoracic regions of a 4-week embryo, illustrating the location of the cartilages in the pharyngeal arches. B, Similar view of a 24-week fetus illustrating the derivatives of the pharyngeal arch cartilages. The mandible is formed by intramembranous ossification of mesenchymal tissue surrounding the first arch cartilage. This cartilage acts as a template for development of the mandible, but does not contribute directly to its formation. Occasionally ossification of the second pharyngeal arch cartilage may extend from the styloid process along the stylohyoid ligament. When this occurs, it may cause pain in the region of the palatine tonsil.
  424. Table 9-1 Structures Derived from Pharyngeal Arch Components*
  425. FIGURE 9-6 A, Lateral view of the head, neck, and thoracic regions of a 4-week embryo showing the muscles derived from the pharyngeal arches. The arrow shows the pathway taken by myoblasts from the occipital myotomes to form the tongue musculature. B, Sketch of the head and neck regions of a 20-week fetus, dissected to show the muscles derived from the pharyngeal arches. Parts of the platysma and sternocleidomastoid muscles have been removed to show the deeper muscles. The myoblasts from the second pharyngeal arch migrate from the neck to the head, where they give rise to the muscles of facial expression. These muscles are supplied by the facial nerve (cranial nerve VII), the nerve of the second pharyngeal arch.
  426. Derivatives of Pharyngeal Pouches
  427. First Pharyngeal Pouch
  428. Second Pharyngeal Pouch
  429. Third Pharyngeal Pouch
  430. FIGURE 9-7 A, Lateral view of the head, neck, and thoracic regions of a 4-week embryo showing the cranial nerves supplying the pharyngeal arches. B, Sketch of the head and neck regions of a 20-week fetus showing the superficial distribution of the two caudal branches of the first pharyngeal arch nerve (cranial nerve V). C, Sagittal section of the fetal head and neck showing the deep distribution of sensory fibers of the nerves to the teeth and mucosa of the tongue, pharynx, nasal cavity, palate, and larynx.
  431. Histogenesis of Thymus
  432. Fourth Pharyngeal Pouch
  433. Histogenesis of Parathyroid and Thyroid Glands
  434. FIGURE 9-8 Schematic horizontal sections at the level shown in Figure 9-4A, illustrating the adult derivatives of the pharyngeal pouches. A, At 5 weeks. Note that the second pharyngeal arch grows over the third and fourth arches, burying the second to fourth pharyngeal grooves in the cervical sinus. B, At 6 weeks. C, At 7 weeks. Note the migration of the developing thymus, parathyroid, and thyroid glands into the neck.
  435. FIGURE 9-9 Schematic sagittal section of the head, neck, and upper thoracic regions of a 20-week fetus showing the adult derivatives of the pharyngeal pouches and the descent of the thyroid gland into the neck.
  436. Pharyngeal Grooves
  437. Pharyngeal Membranes
  438. Cervical (Branchial) Sinuses
  439. Cervical (Branchial) Fistula
  440. Piriform Sinus Fistula
  441. FIGURE 9-10 A, Lateral view of the head, neck, and thoracic regions of a 5-week embryo showing the cervical sinus that is normally present at this stage. B, Horizontal section of the embryo, at the level shown in A, illustrating the relationship of the cervical sinus to the pharyngeal arches and pouches. C, Diagrammatic sketch of the adult pharyngeal and neck regions indicating the former sites of openings of the cervical sinus and pharyngeal pouches. The broken lines indicate possible courses of cervical fistulas. D, Similar sketch showing the embryologic basis of various types of cervical sinus. E, Drawing of a cervical fistula resulting from persistence of parts of the second pharyngeal groove and second pharyngeal pouch. F, Sketch showing possible sites of cervical cysts and the openings of cervical sinuses and fistulas. A branchial vestige is also illustrated (also Fig. 9-14).
  442. FIGURE 9-11 A, A child’s neck showing a catheter inserted into the external opening of a cervical (branchial) sinus. The catheter allows definition of the length of the tract, which facilitates surgical excision. B, A fistulogram of a complete cervical (branchial) fistula. The radiograph was taken after injection of a contrast medium showing the course of the fistula through the neck.
  443. Cervical (Branchial) Cysts
  444. FIGURE 9-12 A swelling in a boy’s neck produced by a cervical cyst. These large cysts often lie free in the neck just inferior to the angle of the mandible, but they may develop anywhere along the anterior border of the sternocleidomastoid muscle as in this case.
  445. FIGURE 9-13 This is a computed tomography (CT) image of the neck region of a 24-year-old woman who presented with a 2-month history of a “lump” in the neck. The low-density cervical cyst, (C) is anterior to the sternocleidomastoid muscle (S). Note the external carotid artery (arrow) and the external jugular vein (dotted arrow).
  446. Branchial Vestiges
  447. First Pharyngeal Arch Syndrome
  448. FIGURE 9-14 A cartilaginous branchial vestige under the skin of a child’s neck.
  449. FIGURE 9-15 An infant with first arch syndrome, a pattern of anomalies resulting from insufficient migration of neural crest cells into the first pharyngeal arch. Note the deformed auricle, the preauricular appendage, the defect in the cheek between the auricle and the mouth, hypoplasia of the mandible, and macrostomia (large mouth).
  450. DiGeorge Syndrome
  451. FIGURE 9-16 Anterior view of the thyroid gland, thymus, and parathyroid glands, illustrating various congenital anomalies that may occur.
  452. Accessory Thymic Tissue
  453. Ectopic Parathyroid Glands
  454. Abnormal Number of Parathyroid Glands
  455. Development of Thyroid Gland
  456. FIGURE 9-17 Development of the thyroid gland. A to C, Schematic sagittal sections of the head and neck regions of embryos at 4, 5, and 6 weeks illustrating successive stages in the development of the thyroid gland. D, Similar section of an adult head and neck showing the path taken by the thyroid gland during its embryonic descent (indicated by the former tract of the thyroglossal duct).
  457. FIGURE 9-18 The anterior surface of a dissected adult thyroid gland showing persistence of the thyroglossal duct. Observe the pyramidal lobe ascending from the superior border of the isthmus. It represents a persistent portion of the inferior end of the thyroglossal duct that has formed thyroid tissue.
  458. Histogenesis of Thyroid Gland
  459. Congenital Hypothyroidism
  460. Thyroglossal Duct Cysts and Sinuses
  461. Ectopic Thyroid Gland
  462. Agenesis of Thyroid Gland
  463. FIGURE 9-19 A, Sketch of the head and neck showing the possible locations of thyroglossal duct cysts. A thyroglossal duct sinus is also illustrated. The broken line indicates the course taken by the thyroglossal duct during descent of the developing thyroid gland from the foramen cecum to its final position in the anterior part of the neck. B, Similar sketch illustrating lingual and cervical thyroglossal duct cysts. Most thyroglossal duct cysts are located just inferior to the hyoid bone.
  464. Development of Tongue
  465. FIGURE 9-20 Large thyroglossal duct cyst (arrow) in a male patient.
  466. FIGURE 9-21 Computed tomography images. A, Level of the thyrohyoid membrane and base of the epiglottis. B, Level of thyroid cartilage, which is calcified. The thyroglossal duct cyst extends cranially to the margin of the hyoid bone.
  467. FIGURE 9-22 Sketch of the head and neck showing the usual sites of ectopic thyroid tissue. The broken line indicates the path followed by the thyroid gland during its descent and the former tract of the thyroglossal duct.
  468. FIGURE 9-23 A, A sublingual thyroid mass in a 5-year-old girl. B, Technetium-99m pertechnetate scan (scintigraphy) showing a sublingual thyroid gland (*) without evidence of functioning thyroid tissue in the anterior part of the neck.
  469. Lingual Papillae and Taste Buds
  470. Nerve Supply of Tongue
  471. FIGURE 9-24 A and B, Schematic horizontal sections through the pharynx at the level shown in Figure 9-4A showing successive stages in the development of the tongue during the fourth and fifth weeks. C, Drawing of the adult tongue showing the pharyngeal arch derivation of the nerve supply of its mucosa.
  472. FIGURE 9-25 An infant with ankyloglossia (tongue-tie). Note the short frenulum, which extends to the tip of the tongue. Ankyloglossia interferes with protrusion of the tongue and may make breast-feeding difficult.
  473. Congenital Anomalies of Tongue
  474. Congenital Lingual Cysts and Fistulas
  475. Ankyloglossia
  476. Macroglossia
  477. Microglossia
  478. Bifid or Cleft Tongue (Glossoschisis)
  479. Development of Salivary Glands
  480. Development of Face
  481. FIGURE 9-26 Diagrams illustrating progressive stages in the development of the human face.
  482. FIGURE 9-27 Scanning electron micrograph of a ventral view of a Carnegie stage 14 embryo (30–32 days).
  483. FIGURE 9-28 Scanning electron micrograph of a ventral view of a human embryo of approximately 33 days (Carnegie stage 15, crown–rump length 8 mm). Observe the prominent frontonasal process (FNP) surrounding the telencephalon (forebrain). Also observe the nasal pits (NP) located in the ventrolateral regions of the frontonasal prominence. Medial and lateral nasal prominences surround these pits. The maxillary prominences (MXP) form the lateral boundaries of the stomodeum. The fusing mandibular prominences (MDP) are located just caudal to the stomodeum. The second pharyngeal arch (BA2) is clearly visible and shows overhanging margins (opercula). The third pharyngeal arch (BA3) is also clearly visible.
  484. FIGURE 9-29 Progressive stages in the development of a human nasal sac (primordial nasal cavity). A, Ventral view of embryo of approximately 28 days. B to E, Transverse sections through the left side of the developing nasal sac.
  485. FIGURE 9-30 Scanning electron micrograph of the craniofacial region of a human embryo of approximately 41 days (Carnegie stage 16, crown–rump length 10.8 mm) viewed obliquely. The maxillary prominence (MXP) appears puffed up laterally and wedged between the lateral (LNP) and medial (MNP) nasal prominences surrounding the nasal pit (NP). The auricular hillocks (AH) can be seen on both sides of the pharyngeal groove between the first and second arches, which will form the external acoustic meatus (EAM). MDP, Mandibular prominence; ST, stomodeum.
  486. FIGURE 9-31 Ventral view of the face of an embryo at Carnegie stage 22, approximately 54 days. Observe that the eyes are widely separated and the ears are low-set at this stage.
  487. FIGURE 9-32 Scanning electron micrograph of the right nasal region of a human embryo of approximately 41 days (Carnegie stage 17, crown–rump length 10.8 mm) showing the maxillary prominence (MXP) fusing with the medial nasal prominence (MNP). Observe the large nasal pit (NP). Epithelial bridges can be seen between these prominences. Observe the furrow representing the nasolacrimal groove between the MXP and the lateral nasal prominence (LNP).
  488. FIGURE 9-33 Early development of the maxilla, palate, and upper lip. A, Facial view of a 5-week embryo. B and C, Sketches of horizontal sections at the levels shown in A. The arrows in C indicate subsequent growth of the maxillary and medial nasal prominences toward the median plane and merging of the prominences with each other. D to F, Similar sections of older embryos illustrating merging of the medial nasal prominences with each other and the maxillary prominences to form the upper lip. Recent studies suggest that the upper lip is formed entirely from the maxillary prominences.
  489. Summary of Facial Development
  490. Atresia of Nasolacrimal Duct
  491. Congenital Auricular Sinuses and Cysts
  492. Development of Nasal Cavities
  493. FIGURE 9-34 Sagittal sections of the head showing development of the nasal cavities. The nasal septum has been removed. A, 5 weeks. B, 6 weeks, showing breakdown of the oronasal membrane. C, 7 weeks, showing the nasal cavity communicating with the oral cavity and development of the olfactory epithelium. D, 12 weeks, showing the palate and the lateral wall of the nasal cavity.
  494. Paranasal Sinuses
  495. FIGURE 9-35 Photomicrograph of a frontal section through the developing oral cavity and nasal regions of a 22-mm human embryo of approximately 54 days. Observe the bilateral, tubular vomeronasal organ.
  496. FIGURE 9-36 A, Sagittal section of the head of a 20-week fetus illustrating the location of the palate. B, The bony palate and alveolar arch of a young adult. The suture between the premaxillary part of the maxilla and the fused palatal processes of the maxillae is usually visible in crania (skulls) of young persons. It is not visible in the hard palates of most dried crania because they are usually from old adults.
  497. Postnatal Development of Paranasal Sinuses
  498. Development of Palate
  499. Primary Palate
  500. Secondary Palate
  501. FIGURE 9-37 A, Sagittal section of the embryonic head at the end of the sixth week showing the median palatal process. B, D, F, and H, Roof of the mouth from the sixth to 12th weeks illustrating the development of the palate. The broken lines in D and F indicate sites of fusion of the palatine processes. The arrows indicate medial and posterior growth of the lateral palatine processes. C, E, and G, Frontal sections of the head illustrating fusion of the lateral palatine processes with each other and the nasal septum and separation of the nasal and oral cavities.
  502. FIGURE 9-38 Frontal sections of human embryonic heads showing development of the lateral palatal processes (P), nasal septum (NS), and tongue (T) during the eighth week. A, Embryo with a crown–rump length (CRL) of 24 mm. This section shows early development of the palatine processes. B, Embryo with a CRL of 27 mm. This section shows the palate just before palatine process elevation. C, Embryo with a CRL of 29 mm (near the end of the eighth week). The palatine processes are elevated and fused.
  503. FIGURE 9-39 Infant with unilateral cleft lip and cleft palate. Clefts of the lip, with or without cleft palate, occur approximately once in 1000 births; most affected infants are males.
  504. Cleft Lip and Cleft Palate
  505. Other Facial Defects
  506. Facial Clefts
  507. FIGURE 9-40 Various types of cleft lip and palate. A, Normal lip and palate. B, Cleft uvula. C, Unilateral cleft of the secondary (posterior) palate. D, Bilateral cleft of the posterior part of the palate. E, Complete unilateral cleft of the lip and alveolar process of the maxilla with a unilateral cleft of the primary (anterior) palate. F, Complete bilateral cleft of the lip and alveolar processes of the maxillae with bilateral cleft of the anterior part of the palate. G, Complete bilateral cleft of the lip and alveolar processes of the maxillae with bilateral cleft of the anterior part of the palate and unilateral cleft of the posterior part of the palate. H, Complete bilateral cleft of the lip and alveolar processes of the maxillae with complete bilateral cleft of the anterior and posterior palate.
  508. FIGURE 9-41 Congenital anomalies of the lip and palate. A, Infant with a left unilateral cleft lip and cleft palate. B, Infant with bilateral cleft lip and cleft palate.
  509. FIGURE 9-42 Drawings illustrating the embryologic basis of complete unilateral cleft lip. A, A 5-week embryo. B, Horizontal section through the head illustrating the grooves between the maxillary prominences and the merging medial nasal prominences. C, A 6-week embryo showing a persistent labial groove on the left side. D, Horizontal section through the head showing the groove gradually filling in on the right side after proliferation of mesenchyme (arrows). E, A 7-week embryo. F, Horizontal section through the head showing that the epithelium on the right has almost been pushed out of the groove between the maxillary and medial nasal prominences. G, A 10-week fetus with a complete unilateral cleft lip. H, Horizontal section through the head after stretching of the epithelium and breakdown of the tissues in the floor of the persistent labial groove on the left side, forming a complete unilateral cleft lip.
  510. FIGURE 9-43 Congenital anomalies of the lip and palate. A, Newborn male infant with unilateral complete cleft lip and cleft palate. B, Intraoral photograph (taken with mirror) showing left unilateral complete cleft of the primary and secondary parts of palate. C, Newborn female infant with bilateral complete cleft lip and cleft palate. D, Intraoral photograph showing bilateral complete cleft palate. Note maxillary protrusion and natal tooth at gingival apex in each lesser segment.
  511. FIGURE 9-44 A, Three-dimensional ultrasound surface rendering of a fetus with unilateral cleft lip. B, Coronal sonogram of a fetal mouth with a cleft lip extending into the left nostril (+). Coronal plane. C, Coronal sonogram of a fetus showing a bilateral cleft lip (arrows), lower lip (L), and chin (C). D, Sagittal magnetic resonance image of a fetus showing the absence of the middle part of the hard palate. Note the fluid above the tongue (t) without the intervening palate.
  512. FIGURE 9-45 Photographs of a child with an oblique facial cleft. Note the persistent nasolacrimal cleft. A, Before surgical correction. B, After surgical correction.
  513. Summary of Pharyngeal Apparatus, Face, and Neck
  514. Clinically Oriented Problems
  515. Case 9–1
  516. Case 9–2
  517. Case 9–3
  518. Case 9–4
  519. Case 9–5
  520. References and Suggested Reading
  521. Chapter 10 Respiratory System
  522. Respiratory Primordium
  523. FIGURE 10-1 A, Lateral view of a 4-week embryo illustrating the relationship of the pharyngeal apparatus to the developing respiratory system. B, Sagittal section of the cranial half of the embryo. C, Horizontal section of the embryo illustrating the floor of the primordial pharynx and the location of the laryngotracheal groove.
  524. Development of Larynx
  525. Laryngeal Atresia
  526. FIGURE 10-2 Successive stages in the development of the tracheoesophageal septum during the fourth and fifth weeks. A to C, Lateral views of the caudal part of the primordial pharynx showing the laryngotracheal diverticulum and partitioning of the foregut into the esophagus and laryngotracheal tube. D to F, Transverse sections illustrating formation of the tracheoesophageal septum and showing how it separates the foregut into the laryngotracheal tube and esophagus. The arrows indicate cellular changes resulting from growth.
  527. FIGURE 10-3 Successive stages in the development of the larynx. A, At 4 weeks. B, At 5 weeks. C, At 6 weeks. D, At 10 weeks. The epithelium lining of the larynx is of endodermal origin. The cartilages and muscles of the larynx arise from mesenchyme in the fourth and sixth pairs of pharyngeal arches. Note that the laryngeal inlet changes in shape from a slit-like opening to a T-shaped inlet as the mesenchyme surrounding the developing larynx proliferates.
  528. Development of Trachea
  529. Tracheoesophageal Fistula
  530. FIGURE 10-4 Transverse sections through the laryngotracheal tube illustrating progressive stages in the development of the trachea. A, 4 weeks. B, 10 weeks. C, 11 weeks (drawing of micrograph in D). Note that endoderm of the tube gives rise to the epithelium and glands of the trachea and that mesenchyme surrounding the tube forms the connective tissue, muscle, and cartilage. D, Photomicrograph of a transverse section of the developing trachea at 12 weeks.
  531. FIGURE 10-5 The four main varieties of tracheoesophageal fistula (TEF). Possible directions of the flow of the contents are indicated by arrows. Esophageal atresia, as illustrated in A, is associated with TEF in more than 85% of cases. B, Fistula between the trachea and esophagus. C, Air cannot enter the distal esophagus and stomach. D, Air can enter the distal esophagus and stomach, and the esophageal and gastric contents may enter the trachea and lungs.
  532. FIGURE 10-6 A, Tracheoesophageal fistula (TEF) in a 17-week male fetus. The upper esophageal segment ends blindly (pointer). B, Contrast radiograph of a neonate with TEF. Note the communication (arrow) between the esophagus (E) and trachea (T). C, Radiograph of esophageal atresia and trachea-esophageal fistula. The blind proximal esophageal sac is clearly visible. Note the air present in the distal GI tract indicating the presence of the tracheo-esophageal fistula. An umbilical venous catheter can also been seen.
  533. Laryngotracheoesophageal Cleft
  534. Tracheal Stenosis and Atresia
  535. Tracheal Diverticulum (Tracheal Bronchus)
  536. Development of Bronchi and Lungs
  537. FIGURE 10-7 Illustrations of the growth of the developing lungs into the splanchnic mesenchyme adjacent to the medial walls of the pericardioperitoneal canals (primordial pleural cavities). Development of the layers of the pleura is also shown. A, 5 weeks. B, 6 weeks.
  538. FIGURE 10-8 Successive stages in the development of the bronchial buds, bronchi, and lungs.
  539. FIGURE 10-9 Diagrammatic sketches of histologic sections illustrating the stages of lung development. A and B, Early stages of lung development. C and D, Note that the alveolocapillary membrane is thin and that some capillaries bulge into the terminal sacs and alveoli.
  540. Maturation of Lungs
  541. Pseudoglandular Stage (6 to 16 Weeks)
  542. Canalicular Stage (16 to 26 Weeks)
  543. Terminal Sac Stage (26 Weeks to Birth)
  544. Alveolar Stage (32 Weeks to 8 Years)
  545. FIGURE 10-10 Photomicrographs of sections of developing embryonic and fetal lungs. A, Pseudoglandular stage, 8 weeks. Note the “glandular” appearance of the lung. B, Canalicular stage, 16 weeks. The lumina of the bronchi and terminal bronchioles are enlarging. C, Canalicular stage, 18 weeks. D, Terminal sac stage, 24 weeks. Observe the thin-walled terminal sacs (primordial alveoli) that have developed at the ends of the respiratory bronchioles. Also observe that the number of capillaries have increased and some of them are closely associated with the developing alveoli.
  546. FIGURE 10-11 Fetal breathing movements (FBMs) seem to play a role in lung growth through their effects on lung cell cycle kinetics by regulating the expression of growth factors, such as platelet-derived growth factors (PDGFs) and insulin-like growth factors (IGFs), and establishing the gradient of thyroid transcription factor 1 (TTF-1) expression at the last stage of lung organogenesis (i.e., late mediators). It is also suggested that FBMs influence the expression of other unknown growth factors (i.e., early mediators) that are responsible for changes in cell cycle kinetics at earlier stages of lung development. FBMs appear to also be required for the accomplishment of the morphologic differentiation of type I and II pneumocytes.
  547. Oligohydramnios and Lung Development
  548. FIGURE 10-12 Congenital lung cysts. A, Chest radiograph (posteroanterior) of an infant showing a large left-sided congenital cystic adenomatoid malformation (arrow). The heart (asterisk) has shifted to the right. Note the chest tube on the left side, which was placed on the initial diagnosis of a pneumothorax (air in pleural cavity). B, Axial computed tomography image of the thorax in an infant with a large right-sided congenital bronchogenic cyst (asterisk).
  549. Lungs of Neonates
  550. Respiratory Distress Syndrome
  551. Lobe of Azygos Vein
  552. Congenital Lung Cysts
  553. Agenesis of Lungs
  554. Lung Hypoplasia
  555. Accessory Lung
  556. Summary of Respiratory System
  557. Clinically Oriented Problems
  558. Case 10–1
  559. Case 10–2
  560. Case 10–3
  561. Case 10–4
  562. References and Suggested Reading
  563. Chapter 11 Alimentary System
  564. FIGURE 11-1 A, Lateral view of a 4-week embryo showing the relationship of the primordial gut to the omphaloenteric duct (yolk sac). B, Drawing of median section of the embryo showing early alimentary system and its blood supply.
  565. Foregut
  566. Development of Esophagus
  567. Esophageal Atresia
  568. Esophageal Stenosis
  569. Development of Stomach
  570. Rotation of Stomach
  571. Mesenteries of Stomach
  572. Omental Bursa
  573. Hypertrophic Pyloric Stenosis
  574. FIGURE 11-2 Development of the stomach and formation of the omental bursa and greater omentum. A, Median section of the abdomen of a 28-day embryo. B, Anterolateral view of the above embryo. C, Embryo of approximately 35 days. D, Embryo of approximately 40 days. E, Embryo of approximately 48 days. F, Lateral view of the stomach and greater omentum of an embryo of approximately 52 days. G, Sagittal section showing the omental bursa and greater omentum. The arrow in F and G indicates the site of the omental foramen.
  575. FIGURE 11-3 Development of stomach and mesenteries and formation of omental bursa. A, Embryo of 5 weeks. B, Transverse section showing clefts in the dorsal mesogastrium. C, Later stage after coalescence of the clefts to form the omental bursa. D, Transverse section showing the initial appearance of the omental bursa. E, The dorsal mesentery has elongated and the omental bursa has enlarged. F and G, Transverse and sagittal sections, respectively, showing elongation of the dorsal mesogastrium and expansion of the omental bursa. H, Embryo of 6 weeks, showing the greater omentum and expansion of the omental bursa. I and J, Transverse and sagittal sections, respectively, showing the inferior recess of the omental bursa and the omental foramen. The arrows in E, F, and I indicate the site of the omental foramen. In J, the arrow indicates the inferior recess of the omental bursa.
  576. FIGURE 11-4 A, Transverse abdominal sonogram demonstrating a pyloric muscle wall thickness of greater than 4 mm (distance between crosses). B, Horizontal image demonstrating a pyloric channel length greater than 14 mm in an infant with hypertrophic pyloric stenosis. C, Contrast radiograph of the stomach in a 1-month-old male infant with pyloric stenosis. Note the narrowed pyloric end (arrow) and the distended fundus (F) of the stomach, filled with contrast material.
  577. Development of Duodenum
  578. Duodenal Stenosis
  579. Duodenal Atresia
  580. FIGURE 11-5 Progressive stages in the development of the duodenum, liver, pancreas, and extrahepatic biliary apparatus. A, Embryo of 4 weeks. B and C, Embryo of 5 weeks. D, Embryo of 6 weeks. The pancreas develops from the dorsal and ventral pancreatic buds that fuse to form the pancreas. Note that the entrance of the bile duct into the duodenum gradually shifts from its initial position to a posterior one. This explains why the bile duct in the adult passes posterior to the duodenum and the head of the pancreas.
  581. FIGURE 11-6 Drawings showing the embryologic basis of the common types of congenital intestinal obstruction. A, Duodenal stenosis. B, Duodenal atresia. C to F, Diagrammatic longitudinal and transverse sections of the duodenum showing (1) normal recanalization (D to D3), (2) stenosis (E to E3), and atresia (F to F3).
  582. FIGURE 11-7 Ultrasound scans of a fetus of 33 weeks showing duodenal atresia. A, An oblique scan showing the dilated, fluid-filled stomach (St) entering the proximal duodenum (D), which is also enlarged because of the atresia (blockage) distal to it. B, Transverse scan illustrating the characteristic “double-bubble” appearance of the stomach and duodenum when there is duodenal atresia.
  583. Development of Liver and Biliary Apparatus
  584. FIGURE 11-8 A, Median section of a 4-week embryo. B, Transverse section of the embryo showing expansion of the peritoneal cavity (arrows). C, Sagittal section of a 5-week embryo. D, Transverse section of the embryo after formation of the dorsal and ventral mesenteries.
  585. Ventral Mesentery
  586. Anomalies of Liver
  587. Extrahepatic Biliary Atresia
  588. Development of Pancreas
  589. FIGURE 11-9 Median section of caudal half of an embryo at the end of the fifth week showing the liver and its associated ligaments. The arrow indicates the communication of the peritoneal cavity with the extraembryonic coelom.
  590. FIGURE 11-10 A to D, Successive stages in the development of the pancreas from the fifth to the eighth weeks. E to G, Diagrammatic transverse sections through the duodenum and developing pancreas. Growth and rotation (arrows) of the duodenum bring the ventral pancreatic bud toward the dorsal bud, where they subsequently fuse.
  591. Histogenesis of Pancreas
  592. Ectopic Pancreas
  593. Annular Pancreas
  594. Development of Spleen
  595. FIGURE 11-11 A and B show the probable basis of an annular pancreas. C, An annular pancreas encircling the duodenum. This birth defect produces complete obstruction (atresia) or partial obstruction (stenosis) of the duodenum.
  596. FIGURE 11-12 A, Left side of the stomach and associated structures at the end of the fifth week. Note that the pancreas, spleen, and celiac trunk are between the layers of the dorsal mesogastrium. B, Transverse section of the liver, stomach, and spleen at the level shown in A, illustrating their relationship to the dorsal and ventral mesenteries. C, Transverse section of a fetus showing fusion of the dorsal mesogastrium with the peritoneum on the posterior abdominal wall. D and E, Similar sections showing movement of the liver to the right and rotation of the stomach. Observe the fusion of the dorsal mesogastrium to the dorsal abdominal wall. As a result, the pancreas becomes retroperitoneal.
  597. Accessory Spleens (Polysplenia)
  598. Midgut
  599. Herniation of Midgut Loop
  600. Rotation of Midgut Loop
  601. Retraction of Intestinal Loops
  602. Fixation of Intestines
  603. FIGURE 11-13 Drawings illustrating herniation, rotation, and retraction of the midgut from the beginning of the 6th week to the 12th week. A, Transverse section through the midgut loop, illustrating the initial relationship of the limbs of the loop to the artery. Note that the midgut loop is in the proximal part of the umbilical cord. B, Later stage showing the beginning of midgut rotation. B1, Illustration of the 90-degree counterclockwise rotation that carries the cranial limb of the midgut to the right. C, At approximately 10 weeks, showing the intestines returning to the abdomen. C1, Illustration of a further rotation of 90 degrees. D, At approximately 11 weeks showing the location of the viscera after retraction of intestines. D1, Illustration of a further 90-degree rotation of the viscera, for a total of 270 degrees. E, Later in the fetal period, showing the cecum rotating to its normal position in the lower right quadrant of the abdomen.
  604. FIGURE 11-14 A, Physiologic hernia in a fetus of approximately 58 days attached to its placenta. Note the herniated intestine (arrow) in the proximal part of the umbilical cord. B, Schematic drawing showing the structures in the distal part of the umbilical cord.
  605. FIGURE 11-15 Illustrations showing the mesenteries and fixation of the intestines. A, Ventral view of the intestines before their fixation. B, Transverse section at the level shown in A. The arrows indicate areas of subsequent fusion, C, Sagittal section at the plane shown in A, illustrating the greater omentum overhanging the transverse colon. The arrows indicate areas of subsequent fusion. D, Ventral view of the intestines after their fixation. E, Transverse section at the level shown in D after disappearance of the mesentery of the ascending and descending colon. F, Sagittal section at the plane shown in D, illustrating fusion of the greater omentum with the mesentery of the transverse colon and fusion of the layers of the greater omentum.
  606. Cecum and Appendix
  607. Congenital Omphalocele
  608. Umbilical Hernia
  609. Gastroschisis
  610. Anomalies of Midgut
  611. Reversed Rotation
  612. Subhepatic Cecum and Appendix
  613. Mobile Cecum
  614. Internal Hernia
  615. Stenosis and Atresia of Intestine
  616. Ileal Diverticulum and Omphaloenteric Remnants
  617. Duplication of Intestine
  618. FIGURE 11-16 Successive stages in the development of the cecum and appendix. A, Embryo of 6 weeks. B, Embryo of 8 weeks. C, Fetus of 12 weeks. D, Fetus at birth. Note that the appendix is relatively long and is continuous with the apex of the cecum. E, Child. Note that the opening of the appendix lies on the medial side of the cecum. In approximately 64% of people, the appendix is located posterior to the cecum (retrocecal). The tenia coli is a thickened band of longitudinal muscle in the wall of the colon.
  619. FIGURE 11-17 A, An infant with a large omphalocele. B, Drawing of the infant with an omphalocele resulting from a median defect of the abdominal muscles, fascia, and skin near the umbilicus. This defect resulted in the herniation of intra-abdominal structures (liver and intestine) into the proximal end of the umbilical cord. It is covered by a membrane composed of peritoneum and amnion.
  620. FIGURE 11-18 Sonogram of the abdomen of a fetus showing a large omphalocele, with the liver (L) protruding (herniating) from the abdomen (*). Also observe the stomach (S).
  621. FIGURE 11-19 A, Photograph of a neonate with viscera protruding from an anterior abdominal wall birth defect—gastroschisis. The defect was 2 to 4 cm long and involved all layers of the abdominal wall. B, Photograph of the infant after the viscera were returned to the abdomen and the defect was surgically closed. C (sagittal) and D (axial) sonograms of a fetus at 18 weeks with gastroschisis. Loops of intestine (arrow) can be seen in the amniotic fluid anterior to the fetus (F).
  622. FIGURE 11-20 Birth defects of midgut rotation. A, Nonrotation. B, Mixed rotation and volvulus. C, Reversed rotation. D, Subhepatic cecum and appendix. E, Internal hernia. F, Midgut volvulus. G, CT enterographic image of nonrotation in an adolescent patient with chronic abdominal pain. The large intestine is completely on the left side of the abdomen (stool-filled). The small intestine (fluid-filled) is seen on the right.
  623. FIGURE 11-21 Photograph of a large ileal diverticulum (Meckel diverticulum). Only a small percentage of these diverticula produce symptoms. Ileal diverticula are one of the most common birth defects of the alimentary tract.
  624. FIGURE 11-22 Ileal diverticula and remnants of the omphaloenteric duct. A, Section of the ileum and a diverticulum with an ulcer. B, A diverticulum connected to the umbilicus by a fibrous remnant of the omphaloenteric duct. C, Omphaloenteric fistula resulting from persistence of the intra-abdominal part of the omphaloenteric duct. D, Omphaloenteric cyst at the umbilicus and in the fibrous remnant of the omphaloenteric duct. E, Volvulus (twisted) ileal diverticulum and an umbilical sinus resulting from the persistence of the omphaloenteric duct in the umbilicus. F, The omphaloenteric duct has persisted as a fibrous cord connecting the ileum with the umbilicus. A persistent vitelline artery extends along the fibrous cord to the umbilicus. This artery carried blood to the umbilical vesicle from the embryo.
  625. FIGURE 11-23 Male neonate with a patent omphaloenteric duct. A, The transected umbilical cord shows two umbilical arteries (A), an umbilical vein (V), and a larger lumen (O) of the omphaloenteric duct. B, An abdominal radiograph identifies contrast material injected through the omphaloenteric duct into the ileum.
  626. FIGURE 11-24 A, Cystic duplication of the small intestine on the mesenteric side of the intestine; it receives branches from the arteries supplying the intestine. B, Longitudinal section of the duplication shown in A; its musculature is continuous with the intestinal wall. C, A short tubular duplication. D, A long duplication showing a partition consisting of the fused muscular walls. E, Transverse section of the intestine during the solid stage. F, Normal vacuole formation. G, Coalescence of the vacuoles and reformation of the lumen. H, Two groups of vacuoles have formed. I, Coalescence of the vacuoles illustrated in H results in intestinal duplication.
  627. Hindgut
  628. Cloaca
  629. Partitioning of Cloaca
  630. FIGURE 11-25 Successive stages in the partitioning of the cloaca into the rectum and urogenital sinus by the urorectal septum. A, C, and E, Views from the left side at 4, 6, and 7 weeks, respectively. B, D, and F, Enlargements of the cloacal region. B1 and D1, Transverse sections of the cloaca at the levels shown in B and D. Note that the postanal portion (shown in B) degenerates and disappears as the rectum forms.
  631. Anal Canal
  632. FIGURE 11-26 Sketch of the rectum and anal canal showing their developmental origins. Note that the superior two thirds of the anal canal are derived from the hindgut, whereas the inferior one third of the canal is derived from the anal pit. Because of their different embryologic origins, the superior and inferior parts of the anal canal are supplied by different arteries and nerves and have different venous and lymphatic drainages.
  633. Congenital Megacolon or Hirschsprung Disease
  634. FIGURE 11-27 Radiograph of the colon after a barium enema in a 1-month-old infant with congenital megacolon (Hirschsprung disease). The aganglionic distal segment (rectum and distal sigmoid colon) is narrow, with distended normal ganglionic bowel, full of fecal material, proximal to it. Note the transition zone (arrow).
  635. Anorectal Anomalies
  636. Low Birth Defects of Anorectal Region
  637. High Birth Defects of Anorectal Region
  638. FIGURE 11-28 Imperforate anus. A, Female neonate with anal atresia (imperforate anus). In most cases, a thin layer of tissue separates the anal canal from the exterior. Some form of imperforate anus occurs approximately once in every 5000 neonates; it is more common in males. B, Radiograph of an infant with an imperforate anus. The dilated end of the radiopaque probe is at the bottom of the blindly ending anal pit. The large intestine is distended with feces and contrast material.
  639. FIGURE 11-29 Various types of anorectal birth defects. A, Persistent cloaca. Note the common outlet for the intestinal, urinary, and reproductive tracts. B, Anal stenosis. C, Anal atresia (imperforate anus). D and E, Anal agenesis with a perineal fistula. F, Anorectal agenesis with a rectovaginal fistula. G, Anorectal agenesis with a rectourethral fistula. H and I, Rectal atresia.
  640. Summary of Alimentary System
  641. Clinically Oriented Problems
  642. Case 11–1
  643. Case 11–2
  644. Case 11–3
  645. Case 11–4
  646. Case 11–5
  647. References and Suggested Reading
  648. Chapter 12 Urogenital System
  649. FIGURE 12-1 A, Dorsal view of an embryo during the third week (approximately 18 days). B, Transverse section of the embryo showing the position of the intermediate mesenchyme before lateral folding of the embryo. C, Lateral view of an embryo during the fourth week (approximately 24 days). D, Transverse section of the embryo after the commencement of folding, showing the nephrogenic cords. E, Lateral view of an embryo later in the fourth week (approximately 26 days). F, Transverse section of the embryo showing the lateral folds meeting each other ventrally.
  650. Development of Urinary System
  651. Development of Kidneys and Ureters
  652. Pronephroi
  653. Mesonephroi
  654. FIGURE 12-2 Illustrations of the three sets of nephric systems in an embryo during the fifth week. A, Lateral view. B, Ventral view. The mesonephric tubules have been pulled laterally; their normal position is shown in A.
  655. FIGURE 12-3 Dissection of the thorax, abdomen, and pelvis of an embryo at approximately 54 days. Observe the large suprarenal glands and the elongated mesonephroi (mesonephric kidneys). Also observe the gonads (testes or ovaries). The phallus will develop into a penis or clitoris depending on the genetic sex of the embryo.
  656. Table 12-1 Derivatives and Vestigial Remains of Embryonic Urogenital Structures*
  657. FIGURE 12-4 Photomicrograph of a transverse section of an embryo at approximately 42 days, showing the mesonephros and developing suprarenal glands.
  658. Metanephroi
  659. FIGURE 12-5 A, Lateral view of a 5-week embryo showing the extent of the early mesonephros and the ureteric bud, the primordium of the metanephros (primordium of the permanent kidney). B, Transverse section of the embryo showing the nephrogenic cords from which the mesonephric tubules develop. C to F, Successive stages in the development of mesonephric tubules between the 5th and 11th weeks. The expanded medial end of the mesonephric tubule is invaginated by blood vessels to form a glomerular capsule.
  660. FIGURE 12-6 Development of the permanent kidney. A, Lateral view of a 5-week embryo showing the ureteric bud, the primordium of the metanephros. B to E, Successive stages in the development of the ureteric bud (fifth to eighth weeks). Observe the development of the kidney: ureter, renal pelvis, calices, and collecting tubules.
  661. FIGURE 12-7 Development of nephrons. A, Nephrogenesis commences around the beginning of the eighth week. B and C, Note that the metanephric tubules, the primordia of the nephrons, connect with the collecting tubules to form uriniferous tubules. D, Observe that nephrons are derived from the metanephrogenic blastema and the collecting tubules are derived from the ureteric bud.
  662. FIGURE 12-8 The kidneys and suprarenal glands of a 28-week fetus (x2). The lobes usually disappear by the end of the first postnatal year. Note the large size of the suprarenal (adrenal) glands.
  663. Positional Changes of Kidneys
  664. FIGURE 12-9 Molecular control of kidney development. A, The ureteric bud requires inductive signals derived from metanephrogenic blastema under control of transcription factors (orange text), such as WT1 and signaling molecules (red text) including glial-derived neurotropic factor (GDNF) and its epithelial receptor, RET. The normal ureteric bud response to these inductive signals is under the control of transcription factors such as Pax2, Lim1, and the FORMIN gene. B, Branching of the ureteric bud is initiated and maintained by interaction with the mesenchyme under the regulation of genes such as Emx2 and specified expression of GDNF and RET at the tips of the invading ureteric bud.
  665. Changes in Blood Supply of Kidneys
  666. Accessory Renal Arteries
  667. FIGURE 12-10 A to D, Diagrammatic ventral views of the abdominopelvic region of embryos and fetuses (sixth to ninth weeks), showing medial rotation and relocation of the kidneys from the pelvis to the abdomen. C and D, Note that as the kidneys relocate (ascend), they are supplied by arteries at successively higher levels and that the hila of the kidneys are directed anteromedially.
  668. FIGURE 12-11 Common variations of renal vessels. A, Multiple renal arteries. B, Note the accessory vessel entering the inferior pole of the kidney and that it is obstructing the ureter and producing an enlarged renal pelvis. C and D, Supernumerary renal veins.
  669. Congenital Anomalies of Kidneys and Ureters
  670. Renal Agenesis
  671. Malrotated Kidney
  672. Ectopic Kidneys
  673. Horseshoe Kidney
  674. Duplications of Urinary Tract
  675. Ectopic Ureter
  676. Cystic Kidney Diseases
  677. FIGURE 12-12 Sonograms of a fetus with unilateral renal agenesis. A, Transverse scan at the level of the lumbar region of the vertebral column (Sp) showing the right kidney (RK) but not the left kidney. B, Transverse scan at a slightly higher level showing the left suprarenal gland (between cursors) within the left renal fossa. C, Bilateral renal agenesis in a male fetus of 19.5 weeks.
  678. FIGURE 12-13 Illustrations of various birth defects of the urinary system. The small sketch to the lower right of each drawing illustrates the probable embryologic basis of the defect. A, Unilateral renal agenesis. B, Right side, pelvic kidney; left side, divided kidney with a bifid ureter. C, Right side, malrotation of the kidney; the hilum is facing laterally; left side, bifid ureter and supernumerary kidney. D, Crossed renal ectopia. The left kidney crossed to the right side and fused with the right kidney. E, Pelvic kidney or discoid kidney, resulting from fusion of the kidneys while they were in the pelvis. F, Supernumerary left kidney resulting from the development of two ureteric buds.
  679. FIGURE 12-14 Sonogram of the pelvis of a fetus at 29 weeks. Observe the low position of the right kidney (RK) near the urinary bladder (BL). This pelvic kidney resulted from its failure to ascend during the sixth to ninth weeks. Observe the normal location of the right suprarenal gland (AD), which develops separately from the kidney.
  680. FIGURE 12-15 Intravenous pyelogram (radiograph) showing crossed renal ectopia (malposition).
  681. FIGURE 12-16 A, Horseshoe kidney in the lower abdomen of a 13-week female fetus. B, Contrast-enhanced computed tomography scan of the abdomen of an infant with a horseshoe kidney. Note the isthmus (vascular) of renal tissue (I) connecting the right and left kidneys just anterior to the aorta (arrow) and inferior vena cava.
  682. FIGURE 12-17 A duplex kidney with two ureters and renal pelves. A, Longitudinal section through the kidney showing two renal pelves and calices. B, Anterior surface of the kidney. C, Intravenous urography showing duplication of the right kidney and ureter in a 10-year-old male. The distal ends of the right ureter are fused at the level of the first sacral vertebra.
  683. FIGURE 12-18 Ectopic ureter in a young girl. This ureter enters the vestibule of the vagina near the external urethral orifice. A thin ureteral catheter with transverse marks has been introduced through the ureteric orifice into the ectopic ureter. This girl had a normal voiding pattern and constant urinary dribbling.
  684. FIGURE 12-19 Cystic kidney disease. A, Computed tomography (CT) scan (contrast enhanced) of the abdomen of a 5-month-old male infant with AR polycystic kidney disease. Note the linear ectasia (cysts) of collecting tubules. B, Ultrasound scan of the left kidney of a 15-day-old male infant showing multiple noncommunicating cysts with no renal tissue (unilateral multicystic dysplastic kidney).
  685. Development of Urinary Bladder
  686. Urachal Anomalies
  687. Congenital Megacystis
  688. Exstrophy of Bladder
  689. FIGURE 12-20 A, Lateral view of 5-week embryo, showing division of the cloaca by the urorectal septum into the urogenital sinus and rectum. B, D, and F, Dorsal views, showing the development of the kidneys and bladder, and changes in the location of the kidneys. C, E, G, and H, Lateral views. The stages shown in G and H are reached by the 12th week.
  690. FIGURE 12-21 Dissection of the abdomen and pelvis of an 18-week female fetus showing the relation of the urachus to the urinary bladder and umbilical arteries.
  691. FIGURE 12-22 Urachal anomalies. A, Urachal cysts; the common site for them is in the superior end of the urachus just inferior to the umbilicus. B, Two types of urachal sinus are shown: one opens into the bladder and the other opens at the umbilicus. C, A urachal fistula connects the bladder and umbilicus.
  692. FIGURE 12-23 Sonogram of an 18-week male fetus with megacystis (enlarged bladder) caused by posterior urethral valves. The cross is placed on the fourth intercostal space, the level to which the diaphragm has been elevated by this very large fetal bladder (arrow; black = urine). In this case, the fetus survived because of the placement of a pigtail catheter within the fetal bladder, allowing drainage of urine into the amniotic cavity.
  693. FIGURE 12-24 Exstrophy (eversion) of the bladder and bifid penis in a male infant. The red bladder mucosa is visible and the halves of the penis and scrotum are widely separated.
  694. FIGURE 12-25 A, C, and E, Normal stages in the development of the infraumbilical abdominal wall and the penis during the fourth to eighth weeks. B, D, and F, Probable stages in the development of epispadias and exstrophy of the bladder. B and D, Note that the mesoderm fails to extend into the anterior abdominal wall anterior to the urinary bladder. Also note that the genital tubercle is located in a more caudal position than usual and that the urethral groove has formed on the dorsal surface of the penis. F, The surface ectoderm and anterior wall of the bladder have ruptured, resulting in exposure of the posterior wall of the bladder. Note that the musculature of the anterior abdominal wall is present on each side of the defect.
  695. Development of Urethra
  696. Development Of Suprarenal Glands
  697. FIGURE 12-26 Schematic longitudinal sections of the developing penis illustrating development of the prepuce (foreskin) and the distal part of the spongy urethra. A, At 11 weeks. B, At 12 weeks. C, At 14 weeks. The epithelium of the spongy urethra has a dual origin; most of it is derived from endoderm of the phallic part of the urogenital sinus; the distal part of the urethra lining the navicular fossa is derived from surface ectoderm.
  698. FIGURE 12-27 Schematic drawings illustrating development of the suprarenal glands. A, At 6 weeks, showing the mesodermal primordium of the fetal cortex. B, At 7 weeks, showing the addition of neural crest cells. C, At 8 weeks, showing the fetal cortex and early permanent cortex beginning to encapsulate the medulla. D and E, Later stages of encapsulation of the medulla by the cortex. F, Gland of a neonate showing the fetal cortex and two zones of the permanent cortex. G, At 1 year, the fetal cortex has almost disappeared. H, At 4 years, showing the adult pattern of cortical zones. Note that the fetal cortex has disappeared and that the gland is much smaller than it was at birth (F).
  699. Congenital Adrenal Hyperplasia and Adrenogenital Syndrome
  700. Development Of Genital System
  701. FIGURE 12-28 External genitalia of a 6-year-old girl showing an enlarged clitoris and fused labia majora that have formed a scrotum-like structure. The arrow indicates the opening into the urogenital sinus. This extreme masculinization is the result of congenital adrenal hyperplasia (CAH).
  702. Development of Gonads
  703. Indifferent Gonads
  704. FIGURE 12-29 A, Sketch of a 5-week embryo illustrating the migration of primordial germ cells from the umbilical vesicle into the embryo. B, Three-dimensional sketch of the caudal region of a 5-week embryo showing the location and extent of the gonadal ridges. C, Transverse section showing the primordium of the suprarenal glands, the gonadal ridges, and the migration of primordial germ cells into the developing gonads. D, Transverse section of a 6-week embryo showing the gonadal cords. E, Similar section at a later stage showing the indifferent gonads and paramesonephric ducts.
  705. Primordial Germ Cells
  706. Chromosomal Basis of Sex Determination
  707. FIGURE 12-30 Photomicrograph of a transverse section of the abdomen of an embryo at approximately 40 days, showing the gonadal ridge, which will develop into a testis or ovary depending on the chromosomal sex of the embryo. Most of the developing gonad is composed of mesenchyme derived from the coelomic epithelium of the gonadal ridge. The large round cells in the gonad are primordial germ cells.
  708. Development of Testes
  709. Development of Ovaries
  710. FIGURE 12-31 Schematic illustrations showing differentiation of the indifferent gonads in a 5-week embryo (top) into ovaries or testes. The left side of the drawing shows the development of testes resulting from the effects of the testis-determining factor (TDF) located on the Y chromosome. Note that the gonadal cords become seminiferous cords, the primordia of the seminiferous tubules. The parts of the gonadal cords that enter the medulla of the testis form the rete testis. In the section of the testis at the bottom left, observe that there are two kinds of cells: spermatogonia, derived from the primordial germ cells, and sustentacular or Sertoli cells, derived from mesenchyme. The right side shows the development of ovaries in the absence of TDF. Cortical cords have extended from the surface epithelium of the gonad and primordial germ cells have entered them. They are the primordia of the oogonia. Follicular cells are derived from the surface epithelium of the ovary.
  711. FIGURE 12-32 Transverse sections of gonads of human fetuses. A, Section of a testis from a male fetus born prematurely at 21 weeks, showing seminiferous tubules. B, Section of an ovary from a 14-day-old female infant that died. Observe the numerous primordial follicles in the cortex, each of which contains a primary oocyte. The arrow indicates the relatively thin surface epithelium of the ovary (x275).
  712. Development of Genital Ducts
  713. Development of Male Genital Ducts and Glands
  714. FIGURE 12-33 Schematic drawings illustrating development of the male and female reproductive systems from the genital ducts and urogenital sinus. Vestigial structures are also shown. A, Reproductive system in a male neonate. B, Female reproductive system in a 12-week fetus. C, Reproductive system in a female neonate.
  715. FIGURE 12-34 A, Sketch of a ventral view of the posterior abdominal wall of a 7-week embryo showing the two pairs of genital ducts present during the indifferent stage of sexual development. B, Lateral view of a 9-week fetus showing the sinus tubercle on the posterior wall of the urogenital sinus. It becomes the hymen in females and the seminal colliculus in males. The colliculus is an elevated part of the urethral crest on the posterior wall of the prostatic urethra.
  716. Seminal Glands
  717. Prostate
  718. Bulbourethral Glands
  719. Development of Female Genital Ducts and Glands
  720. Auxiliary Genital Glands in Females
  721. Development of Vagina
  722. FIGURE 12-35 A, Dorsal view of the developing prostate in an 11-week fetus. B, Sketch of a median section of the developing urethra and prostate showing numerous endodermal outgrowths from the prostatic urethra. The vestigial prostatic utricle is also shown. C, Section of the prostate (16 weeks) at the level shown in B.
  723. Vestigial Remains of Embryonic Genital Ducts
  724. FIGURE 12-36 Early development of the ovaries and uterus. A, Schematic drawing of a sagittal section of the caudal region of an 8-week female embryo. B, Transverse section showing the paramesonephric ducts approaching each other. C, Similar section at a more caudal level illustrating fusion of the paramesonephric ducts. A remnant of the septum that separates the paramesonephric ducts is shown. D, Similar section showing the uterovaginal primordium, broad ligament, and pouches in the pelvic cavity. Note that the mesonephric ducts have regressed.
  725. Mesonephric Duct Remnants in Males
  726. Mesonephric Duct Remnants in Females
  727. Paramesonephric Duct Remnants in Males
  728. Paramesonephric Duct Remnants in Females
  729. Development Of External Genitalia
  730. Development of Male External Genitalia
  731. FIGURE 12-37 Development of external genitalia. A and B, Diagrams illustrating the appearance of the genitalia during the indifferent stage (fourth to seventh weeks). C, E, and G, Stages in the development of male external genitalia at 9, 11, and 12 weeks, respectively. To the left are schematic transverse sections of the developing penis illustrating formation of the spongy urethra. D, F, and H, Stages in the development of female external genitalia at 9, 11, and 12 weeks, respectively. The mons pubis is a pad of fatty tissue over the symphysis pubis.
  732. FIGURE 12-38 Scanning electron micrographs of the developing external genitalia. A, The perineum during the indifferent stage of a 17-mm, 7-week embryo (x100). 1, developing glans of penis with the ectodermal cord; 2, urethral groove continuous with the urogenital sinus; 3, urethral folds; 4, labioscrotal swellings; 5, anus. B, The external genitalia of a 7.2-cm, 10-week female fetus (x45). 1, glans of clitoris; 2, external urethral orifice; 3, opening into urogenital sinus; 4, urethral fold (primordium of labium minus); 5, labioscrotal swelling (labium majus); 6, anus. C, The external genitalia of a 5.5-cm, 10-week male fetus (x40). 1, glans of penis with ectodermal cord; 2, remains of urethral groove; 3, urethral folds in the process of closing; 4, labioscrotal swellings fusing to form the scrotal raphe; 5, anus.
  733. Development of Female External Genitalia
  734. Determination of Fetal Sex
  735. Ovotesticular DSD
  736. 46 XX, DSD
  737. 46 XY, DSD
  738. FIGURE 12-39 Sonogram of a 33-week male fetus showing normal external genitalia. Observe the penis (arrow) and scrotum (S). Also note the testes in the scrotum.
  739. FIGURE 12-40 Schematic lateral views of the female urogenital system. A, Normal. B, Female with 46 XX, DSD caused by congenital adrenal hyperplasia (CAH). Note the enlarged clitoris and persistent urogenital sinus that were induced by androgens produced by the hyperplastic suprarenal glands.
  740. Androgen Insensitivity Syndrome
  741. Mixed Gonadal Dysgenesis
  742. FIGURE 12-41 A, Photograph of a 17-year-old woman with androgen insensitivity syndrome (AIS). The external genitalia are female, but she has a 46, XY karyotype and testes in the inguinal region. B, Photomicrograph of a section through a testis removed from the inguinal region of this woman showing seminiferous tubules lined by Sertoli cells. There are no germ cells and the interstitial cells are hypoplastic.
  743. Hypospadias
  744. FIGURE 12-42 Glanular hypospadias in an infant. The external urethral orifice is on the ventral surface of the glans of the penis (arrow).
  745. Epispadias
  746. Agenesis of External Genitalia
  747. Bifid Penis and Double Penis
  748. Micropenis
  749. FIGURE 12-43 Perineum of an infant with agenesis of the external genitalia. There are no external genitalia.
  750. Anomalies of Uterine Tubes, Uterus, and Vagina
  751. Absence of Vagina and Uterus
  752. Vaginal Atresia
  753. FIGURE 12-44 Uterine anomalies. A, Normal uterus and vagina. B, Double uterus (uterus didelphys) and double vagina (vagina duplex). Note the septum separating the vagina into two parts. C, Double uterus with single vagina. D, Bicornuate uterus (two uterine horns). E, Bicornuate uterus with a rudimentary left horn. F, Septate uterus; the septum separates the body of the uterus. G, Unicorn uterus; only one lateral horn exists.
  754. FIGURE 12-45 Sonogram of bicornuate uterus. A, Axial sonogram of the uterine fundus showing two separate endometrial canals with a 1-week chorionic (gestational) sac (arrow). B, A three-dimensional ultrasound scan of the same patient with a 4-week chorionic sac (arrow) on the right of a uterine septum (S). C, Coronal ultrasound scan of a uterus with a large septum (S) extending down to the cervix.
  755. FIGURE 12-46 A to F, Congenital anomalies of the hymen. The normal appearance of the hymen is illustrated in A and in the inset photograph. Inset, Normal crescentic hymen in a prepubertal child.
  756. Development Of Inguinal Canals
  757. Abnormal Sex Chromosome Complexes
  758. FIGURE 12-47 Formation of the inguinal canals and descent of the testes. A, Sagittal section of a 7-week embryo showing the testis before its descent from the dorsal abdominal wall. B and C, Similar sections at approximately 28 weeks showing the processus vaginalis and the testis beginning to pass through the inguinal canal. Note that the processus vaginalis carries fascial layers of the abdominal wall before it. D, Frontal section of a fetus approximately 3 days later illustrating descent of the testis posterior to the processus vaginalis. The processus has been cut away on the left side to show the testis and ductus deferens. E, Sagittal section of a male neonate showing the processus vaginalis communicating with the peritoneal cavity by a narrow stalk. F, Similar section of a 1-month-old male infant after obliteration of the stalk of the processus vaginalis. Note that the extended fascial layers of the abdominal wall now form the coverings of the spermatic cord.
  759. Relocation Of Testes And Ovaries
  760. Testicular Descent
  761. Ovarian Descent
  762. Cryptorchidism
  763. Ectopic Testes
  764. Congenital Inguinal Hernia
  765. Hydrocele
  766. Summary Of Urogenital System
  767. FIGURE 12-48 Possible sites of cryptorchid and ectopic testes. A, Positions of cryptorchid testes, numbered in order of frequency. B, Usual locations of ectopic testes.
  768. FIGURE 12-49 Diagrams of sagittal sections illustrating conditions resulting from failure of closure of the processus vaginalis. A, Incomplete congenital inguinal hernia resulting from persistence of the proximal part of the processus vaginalis. B, Complete congenital inguinal hernia into the scrotum resulting from persistence of the processus vaginalis. Cryptorchidism, a commonly associated anomaly, is also illustrated. C, Large hydrocele that resulted from an unobliterated portion of the processus vaginalis. D, Hydrocele of the testis and spermatic cord resulting from peritoneal fluid passing into an unclosed processus vaginalis.
  769. Clinically Oriented Problems
  770. Case 12–1
  771. Case 12–2
  772. Case 12–3
  773. Case 12–4
  774. Case 12–5
  775. Case 12–6
  776. References and Suggested Reading
  777. Chapter 13 Cardiovascular System
  778. FIGURE 13-1 Early development of the heart. A, Drawing of a dorsal view of an embryo (approximately 18 days). B, Transverse section of the embryo showing the angioblastic cords in the cardiogenic mesoderm and their relationship to the pericardial coelom. C, Longitudinal section of the embryo illustrating the relationship of the angioblastic cords to the oropharyngeal membrane, pericardial coelom, and septum transversum.
  779. Early Development Of The Heart And Blood Vessels
  780. Development of Veins Associated with Embryonic Heart
  781. FIGURE 13-2 Drawing of the embryonic cardiovascular system (approximately 26 days), showing vessels on the left side. The umbilical vein carries well-oxygenated blood and nutrients from the chorionic sac to the embryo. The umbilical arteries carry poorly oxygenated blood and waste products from the embryo to the chorionic sac (the outermost embryonic membrane).
  782. FIGURE 13-3 Endovaginal scan of a 4-week embryo. A, Bright (echogenic) 2.4-mm embryo (calipers). B, Cardiac activity of 116 beats per minute demonstrated with motion mode. Calipers used to encompass two beats.
  783. Development of Inferior Vena Cava
  784. FIGURE 13-4 Illustrations of the primordial veins of embryo bodies (ventral views). Initially, three systems of veins are present: the umbilical veins from the chorion, the vitelline veins from the umbilical vesicle, and the cardinal veins from the body of the embryos. Next the subcardinal veins appear, and finally the supracardinal veins develop. A, At 6 weeks. B, At 7 weeks. C, At 8 weeks. D, Adult. This drawing illustrates the transformations that produce the adult venous pattern.
  785. FIGURE 13-5 Dorsal views of the developing heart. A, During the fourth week (approximately 24 days), showing the primordial atrium, sinus venosus and veins draining into them. B, At 7 weeks, showing the enlarged right sinus horn and venous circulation through the liver. The organs are not drawn to scale. C, At 8 weeks, indicating the adult derivatives of the cardinal veins shown in A and B.
  786. FIGURE 13-6 CT scan showing a duplicated superior vena cava. Note the aorta (A), the right superior vena cava (R, unopacified), and the left superior vena cava (L, with contrast from left arm injection).
  787. Anomalies of Venae Cavae
  788. Double Superior Venae Cavae
  789. Left Superior Vena Cava
  790. Absence of Hepatic Segment of Inferior Vena Cava
  791. Double Inferior Venae Cavae
  792. Pharyngeal Arch Arteries and Other Branches of Dorsal Aortae
  793. Intersegmental Arteries
  794. Fate of Vitelline and Umbilical Arteries
  795. Later Development Of The Heart
  796. FIGURE 13-7 Drawings showing fusion of the heart tubes and looping of the tubular heart. A to C, Ventral views of the developing heart and pericardial region (22–35 days). The ventral pericardial wall has been removed to show the developing myocardium and fusion of the two heart tubes to form a tubular heart. The endothelium of the heart tube forms the endocardium of the heart. D and E, As the straight tubular heart elongates, it bends and undergoes looping, which forms a D-loop that produces a S-shaped heart.
  797. FIGURE 13-8 A, Dorsal view of an embryo (approximately 20 days). B, Schematic transverse section of the heart region of the embryo illustrated in A, showing the two heart tubes and the lateral folds of the body. C, Transverse section of a slightly older embryo showing the formation of the pericardial cavity and fusion of the heart tubes. D, Similar section (approximately 22 days) showing the tubular heart suspended by the dorsal mesocardium. E, Schematic drawing of the heart (approximately 28 days) showing degeneration of the central part of the dorsal mesocardium and formation of the transverse pericardial sinus. The tubular heart now has a D-loop. F, Transverse section of the embryo at the level indicated in E, showing the layers of the heart wall.
  798. FIGURE 13-9 Longitudinal sections through the cranial half of embryos during the fourth week, showing the effect of the head fold (arrows) on the position of the heart and other structures. A and B, As the head fold develops, the tubular heart and pericardial cavity move ventral to the foregut and caudal to the oropharyngeal membrane. C, Note that the positions of the pericardial cavity and septum transversum have reversed with respect to each other. The septum transversum now lies posterior to the pericardial cavity, where it will form the central tendon of the diaphragm.
  799. Circulation through the Primordial Heart
  800. FIGURE 13-10 A, Sagittal section of the heart at approximately 24 days, showing blood flow through it (arrows). B, Dorsal view of the heart at approximately 26 days, showing the horns of the sinus venosus and the dorsal location of the primordial atrium. C, Ventral view of the heart and pharyngeal arch arteries (approximately 35 days). The ventral wall of the pericardial sac has been removed to show the heart in the pericardial cavity.
  801. FIGURE 13-11 A and B, Sagittal sections of the heart during the fourth and fifth weeks, illustrating blood flow through the heart and division of the atrioventricular canal. The arrows are passing through the sinuatrial (SA) orifice. C, Fusion of the atrioventricular endocardial cushions. D, Coronal section of the heart at the plane shown in C. Note that the septum primum and interventricular septa have started to develop.
  802. Partitioning of Primordial Heart
  803. Partitioning of Atrioventricular Canal
  804. Partitioning of Primordial Atrium
  805. FIGURE 13-12 Drawings of the heart showing partitioning of the atrioventricular (AV) canal, primordial atrium, and ventricle. A, Sketch showing the plane of the sections. B, Frontal section of the heart during the fourth week (approximately 28 days) showing the early appearance of the septum primum, interventricular septum, and dorsal atrioventricular endocardial cushion. C, Similar section of the heart (approximately 32 days) showing perforations in the dorsal part of the septum primum. D, Section of the heart (approximately 35 days) showing the foramen secundum. E, Section of the heart (at approximately 8 weeks, showing the heart after it is partitioned into four chambers. The arrow indicates the flow of well-oxygenated blood from the right into the left atrium. F, Sonogram of a second trimester fetus showing the four chambers of the heart. Note the septum secundum (arrow).
  806. FIGURE 13-13 Diagrammatic sketches illustrating progressive stages in partitioning of the primordial atrium. A to H, Sketches of the developing interatrial septum as viewed from the right side. A1 to H1 are coronal sections of the developing interatrial septum. As the septum secundum grows, note that it overlaps the opening in the septum primum, the foramen secundum. Observe the valve of the oval foramen in G1 and H1. When pressure in the right atrium exceeds that in the left atrium, blood passes from the right to the left side of the heart. When the pressures are equal or higher in the left atrium, the valve closes the oval foramen (G1).
  807. Changes in Sinus Venosus
  808. FIGURE 13-14 Diagrams illustrating the relationship of the septum primum to the oval foramen and septum secundum. A, Before birth, well-oxygenated blood is shunted from the right atrium through the oval foramen into the left atrium when the pressure increases. When the pressure decreases in the right atrium, the flap-like valve of the oval foramen is pressed against the relatively rigid septum secundum. This closes the oval foramen. B, After birth, the pressure in the left atrium increases as the blood returns from the lungs. Eventually the septum primum is pressed against the septum secundum and adheres to it, permanently closing the oval foramen and forming the oval fossa.
  809. FIGURE 13-15 Diagrams illustrating the fate of the sinus venosus. A, Dorsal view of the heart (approximately 26 days) showing the primordial atrium and sinus venosus. B, Dorsal view at 8 weeks after incorporation of the right horn of the sinus venosus into the right atrium. The left horn of the sinus horn becomes the coronary sinus. C, Internal view of the fetal right atrium showing: (1) the smooth part of the wall of the right atrium (sinus venarum) that is derived from the right horn of the sinus venosus and (2) the crista terminalis and valves of the inferior vena cava and coronary sinus that are derived from the right sinuatrial valve. The primordial right atrium becomes the right auricle, a conical muscular pouch.
  810. Primordial Pulmonary Vein and Formation of Left Atrium
  811. FIGURE 13-16 Diagrammatic sketches illustrating absorption of the pulmonary vein into the left atrium. A, At 5 weeks, showing the primordial pulmonary vein opening into the primordial left atrium. B, Later stage showing partial absorption of the primordial pulmonary vein. C, At 6 weeks, showing the openings of two pulmonary veins into the left atrium resulting from absorption of the primordial pulmonary vein. D, At 8 weeks, showing four pulmonary veins with separate atrial orifices. The primordial left atrium becomes the left auricle, a tubular appendage of the atrium. Most of the left atrium is formed by absorption of the primordial pulmonary vein and its branches.
  812. Anomalous Pulmonary Venous Connections
  813. Partitioning of Primordial Ventricle
  814. FIGURE 13-17 Schematic diagrams illustrating partitioning of the primordial heart. A, Sagittal section late in the fifth week showing the cardiac septa and foramina. B, Coronal section at a slightly later stage illustrating the directions of blood flow through the heart (blue arrows) and expansion of the ventricles (black arrows).
  815. Fetal Cardiac Ultrasonography
  816. Partitioning of Bulbus Cordis and Truncus Arteriosus
  817. FIGURE 13-18 Sketches illustrating incorporation of the bulbus cordis into the ventricles and partitioning of the bulbus cordis and truncus arteriosus into the aorta and pulmonary trunk. A, Sagittal section at 5 weeks showing the bulbus cordis as one of the chambers of the primordial heart. B, Schematic coronal section at 6 weeks, after the bulbus cordis has been incorporated into the ventricles to become the conus arteriosus of the right ventricle, which gives origin to the pulmonary trunk and the aortic vestibule of the left ventricle. The arrow indicates blood flow. C to E, Schematic drawings illustrating closure of the interventricular foramen and formation of the membranous part of the interventricular septum. The walls of the truncus arteriosus, bulbus cordis, and right ventricle have been removed. C, At 5 weeks, showing the bulbar ridges and fused atrioventicular endocardial cushions. D, At 6 weeks, showing how proliferation of subendocardial tissue diminishes the interventricular foramen. E, At 7 weeks, showing the fused bulbar ridges, the membranous part of the interventricular septum formed by extensions of tissue from the right side of the atrioventricular endocardial cushions, and closure of the interventricular foramen.
  818. FIGURE 13-19 Schematic sections of the heart illustrating successive stages in the development of the atrioventricular valves, tendinous cords, and papillary muscles. A, At 5 weeks. B, At 6 weeks. C, At 7 weeks. D, At 20 weeks, showing the conducting system of the heart.
  819. FIGURE 13-20 A, Ultrasound image showing the four-chamber view of the heart in a fetus of approximately 20 weeks gestation. B, Orientation sketch (modified from the AIUM Technical Bulletin, Performance of the Basic Fetal Cardiac Ultrasound Examination). The scan was obtained across the fetal thorax. The ventricles and atria are well formed and two atrioventricular (AV) valves are present. The moderator band is one of the trabeculae carneae that carries part of the right branch of the AV bundle. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
  820. FIGURE 13-21 Partitioning of the bulbus cordis and truncus arteriosus. A, Ventral aspect of heart at 5 weeks. The broken lines and arrows indicate the levels of the sections shown in A. B, Transverse sections of the truncus arteriosus and bulbus cordis, illustrating the truncal and bulbar ridges. C, The ventral wall of the heart and truncus arteriosus has been removed to demonstrate these ridges. D, Ventral aspect of heart after partitioning of the truncus arteriosus. The broken lines and arrows indicate the levels of the sections shown in E. E, Sections through the newly formed aorta (A) and pulmonary trunk (PT), showing the aorticopulmonary septum. F, 6 weeks. The ventral wall of the heart and pulmonary trunk have been removed to show the aorticopulmonary septum. G, Diagram illustrating the spiral form of the aorticopulmonary septum. H, Drawing showing the great arteries (ascending aorta and pulmonary trunk) twisting around each other as they leave the heart.
  821. Development of Cardiac Valves
  822. FIGURE 13-22 Development of the semilunar valves of the aorta and pulmonary trunk. A, Sketch of a section of the truncus arteriosus and bulbus cordis showing the valve swellings. B, Transverse section of the bulbus cordis. C, Similar section after fusion of the bulbar ridges. D, Formation of the walls and valves of the aorta and pulmonary trunk. E, Rotation of the vessels has established the adult relations of the valves. F and G, Longitudinal sections of the aorticoventricular junction illustrating successive stages in the hollowing (arrows) and thinning of the valve swellings to form the valve cusps.
  823. Conducting System of Heart
  824. Sudden Infant Death Syndrome
  825. Birth Defects Of The Heart And Great Vessels
  826. Dextrocardia
  827. Ectopia Cordis
  828. Atrial Septal Defects
  829. FIGURE 13-23 The embryonic heart tube during the fourth week. A, Normal looping of the tubular heart to the right. B, Abnormal looping of the tubular heart to the left.
  830. FIGURE 13-24 Neonate with ectopia cordis, cleft sternum, and bilateral cleft lip. Death occurred in the first days of life from infection, cardiac failure, and hypoxia.
  831. FIGURE 13-25 A, Normal postnatal appearance of the right side of the interatrial septum after adhesion of the septum primum to the septum secundum. A1, Sketch of a section of the interatrial septum illustrating formation of the oval fossa in the right atrium. Note that the floor of the oval fossa is formed by the septum primum. B and B1, Similar views of a probe patent oval foramen resulting from incomplete adhesion of the septum primum to the septum secundum. Some well-oxygenated blood can enter the right atrium via a patent oval foramen; however, if the opening is small it usually of no hemodynamic significance.
  832. FIGURE 13-26 Drawings of the right aspect of the interatrial septum. The adjacent sketches of sections of the septa illustrate various types of atrial septal defect (ASD). A, Patent oval foramen resulting from resorption of the septum primum in abnormal locations. B, Patent oval foramen caused by excessive resorption of the septum primum (short flap defect). C, Patent oval foramen resulting from an abnormally large oval foramen. D, Patent oval foramen resulting from an abnormally large oval foramen and excessive resorption of the septum primum. E, Endocardial cushion defect with primum-type ASD. The adjacent section shows the cleft in the anterior cusp of the mitral valve. F, Sinus venosus ASD. The high septal defect resulted from abnormal absorption of the sinus venosus into the right atrium. In E and F, note that the oval fossa has formed normally.
  833. FIGURE 13-27 Dissection of an adult heart with a large patent oval foramen. The arrow passes through a large atrial septal defect (ASD), which resulted from an abnormally large oval foramen and excessive resorption of the septum primum. This is referred to as a secundum-type ASD and is one of the most common types of congenital heart disease.
  834. FIGURE 13-28 A, An infant’s heart, sectioned and viewed from the right side, showing a patent oval foramen and an atrioventricular septal defect. B, Schematic drawing of a heart illustrating various septal defects. ASD, atrial septal defect; VSD, and ventricular septal defect.
  835. Ventricular Septal Defects
  836. FIGURE 13-29 A, Ultrasound image of the heart of a second-trimester fetus with an atrioventricular (AV) canal (atrioventricular septal) defect. An atrial septal defect and ventricular septal defect are also present. Ao, aorta. B, Orientation drawing.
  837. FIGURE 13-30 Ultrasound scan of a fetal heart at 23.4 weeks with an atrioventricular septal defect and a large ventricular septal defect (VSD).
  838. Persistent Truncus Arteriosus
  839. Aorticopulmonary Septal Defect
  840. Transposition of the Great Arteries
  841. FIGURE 13-31 Illustrations of the common types of persistent truncus arteriosus (PTA). A, The common trunk divides into the aorta and a short pulmonary trunk. B, Coronal section of the heart shown in A. Observe the circulation of blood in this heart (arrows) and the ventricular septal defect. C, The right and left pulmonary arteries arise close together from the truncus arteriosus. D, The pulmonary arteries arise independently from the sides of the truncus arteriosus. E, No pulmonary arteries are present; the lungs are supplied by the bronchial arteries. LA, left atrium; RA, right atrium.
  842. FIGURE 13-32 Drawing of a heart illustrating transposition of the great arteries (TGA). The ventricular and atrial septal defects allow mixing of the arterial and venous blood. This birth defect is often associated with other cardiac defects as shown (ventricular septal defect [VSD] and atrial septal defect [ASD]).
  843. Unequal Division of the Truncus Arteriosus
  844. Tetralogy of Fallot
  845. FIGURE 13-33 A, Drawing of an infant’s heart showing a small pulmonary trunk (pulmonary stenosis) and a large aorta resulting from unequal partitioning of the truncus arteriosus. There is also hypertrophy of the right ventricle and a patent ductus arteriosus (PDA). B, Frontal section of this heart illustrating the tetralogy of Fallot. Observe the four cardiac defects of this tetralogy: pulmonary valve stenosis, ventricular septal defect (VSD), overriding aorta, and hypertrophy of the right ventricle.
  846. FIGURE 13-34 Abnormal division of the truncus arteriosus (TA). A to C, Sketches of transverse sections of the TA illustrating normal and abnormal partitioning of the TA. A, Normal. B, Unequal partitioning of the TA resulting in a small pulmonary trunk. C, Unequal partitioning resulting in a small aorta. D, Sketches illustrating a normal semilunar valve and stenotic pulmonary and aortic valves.
  847. FIGURE 13-35 A, Ultrasound image of the heart of a 20-week fetus with tetralogy of Fallot. Note that the large overriding aorta (AO) straddles the interventricular septum. As a result, it receives blood from the left (LV) and right (RV) ventricles. IVS, Interventricular septum; LA, left atrium. B, Orientation drawing.
  848. FIGURE 13-36 Tetralogy of Fallot. Fine barium powder was injected into the heart. Note the two ventricles (V), interventricular septum (I), interventricular septal defect at the superior margin, and origin of the aorta above the right ventricle (overriding aorta). The main pulmonary artery is not visualized.
  849. Aortic Stenosis and Aortic Atresia
  850. Hypoplastic Left Heart Syndrome
  851. FIGURE 13-37 A, Ultrasound image of the heart of a second-trimester fetus with a hypoplastic left heart. Note that the left ventricle (LV) is much smaller than the right ventricle (RV). This is an oblique scan of the fetal thorax through the long axis of the ventricles. B, Orientation drawing.
  852. Derivatives Of Pharyngeal Arch Arteries
  853. Derivatives of First Pair of Pharyngeal Arch Arteries
  854. Derivatives of Second Pair of Pharyngeal Arch Arteries
  855. FIGURE 13-38 Pharyngeal arches and pharyngeal arch arteries. A, Left side of an embryo (approximately 26 days). B, Schematic drawing of this embryo showing the left pharyngeal arch arteries arising from the aortic sac, running through the pharyngeal arches, and terminating in the left dorsal aorta. C, An embryo (approximately 37 days) showing the single dorsal aorta and that most of the first two pairs of pharyngeal arch arteries have degenerated.
  856. Derivatives of Third Pair of Pharyngeal Arch Arteries
  857. Derivatives of Fourth Pair of Pharyngeal Arch Arteries
  858. Fate of Fifth Pair of Pharyngeal Arch Arteries
  859. FIGURE 13-39 Schematic drawings illustrating the arterial changes that result during transformation of the truncus arteriosus, aortic sac, pharyngeal arch arteries, and dorsal aortae into the adult arterial pattern. The vessels that are not colored are not derived from these structures. A, Pharyngeal arch arteries at 6 weeks; by this stage, the first two pairs of arteries have largely disappeared. B, Pharyngeal arch arteries at 7 weeks; the parts of the dorsal aortae and pharyngeal arch arteries that normally disappear are indicated with broken lines. C, Arterial arrangement at 8 weeks. D, Sketch of the arterial vessels of a 6-month-old infant. Note that the ascending aorta and pulmonary arteries are considerably smaller in C than in D. This represents the relative flow through these vessels at the different stages of development. Observe the large size of the ductus arteriosus (DA) in C and that it is essentially a direct continuation of the pulmonary trunk. The DA normally becomes functionally closed within the first few days after birth. Eventually the DA becomes the ligamentum arteriosum, as shown in D.
  860. Derivatives of Sixth Pair of Pharyngeal Arch Arteries
  861. Pharyngeal Arch Arterial Birth Defects
  862. FIGURE 13-40 The relation of the recurrent laryngeal nerves to the pharyngeal arch arteries. A, At 6 weeks, showing the recurrent laryngeal nerves hooked around the sixth pair of pharyngeal arch arteries. B, At 8 weeks, showing the right recurrent laryngeal nerve hooked around the right subclavian artery, and the left recurrent laryngeal nerve hooked around the ductus arteriosus and the arch of the aorta. C, After birth, showing the left recurrent nerve hooked around the ligamentum arteriosum and the arch of the aorta.
  863. FIGURE 13-41 A, Postductal coarctation of the aorta. B, Diagrammatic representation of the common routes of collateral circulation that develop in association with postductal coarctation of the aorta. C and D, Preductal coarctation. E, Sketch of the pharyngeal arch arterial pattern in a 7-week embryo, showing the areas that normally involute (see dotted branches of arteries). Note that the distal segment of the right dorsal aorta normally involutes as the right subclavian artery develops. F, Abnormal involution of a small distal segment of the left dorsal aorta. G, Later stage showing the abnormally involuted segment appearing as a coarctation of the aorta. This moves to the region of the ductus arteriosus with the left subclavian artery. These drawings (E to G) illustrate one hypothesis about the embryologic basis of coarctation of the aorta.
  864. FIGURE 13-42 A, Drawing of the embryonic pharyngeal arch arteries illustrating the embryologic basis of the right and left arches of the aorta (double arch of aorta). B, A large right arch of the aorta and a small left arch of the aorta arise from the ascending aorta and form a vascular ring around the trachea and esophagus. Observe that there is compression of the esophagus and trachea. The right common carotid and subclavian arteries arise separately from the large right arch of the aorta.
  865. Right Arch of Aorta
  866. Anomalous Right Subclavian Artery
  867. FIGURE 13-43 A, Sketch of the pharyngeal arch arteries showing the normal involution of the distal portion of the left dorsal aorta. There is also persistence of the entire right dorsal aorta and the distal part of the right sixth pharyngeal arch artery. B, Right pharyngeal arch artery without a retroesophageal component. C, Right arch of the aorta with a retroesophageal component. The abnormal right arch of the aorta and the ligamentum arteriosum (postnatal remnant of the ductus arteriosus) form a ring that compresses the esophagus and trachea.
  868. FIGURE 13-44 Sketches illustrating the possible embryologic basis of abnormal origin of the right subclavian artery. A, The right fourth pharyngeal arch artery and the cranial part of the right dorsal aorta have involuted. As a result, the right subclavian artery forms from the right seventh intersegmental artery and the distal segment of the right dorsal aorta. B, As the arch of the aorta forms, the right subclavian artery is carried cranially (arrows) with the left subclavian artery. C, The abnormal right subclavian artery arises from the aorta and passes posterior to the trachea and esophagus.
  869. FIGURE 13-45 Abnormal origin of right subclavian artery. This left anterior oblique view of an aortic arch arteriogram shows both common carotid arteries arising from a common stem of the arch of the aorta (BT). The origin of the right subclavian artery (RS) is distal to the separate origin of the left subclavian artery (LS), but is superimposed in this view. The right subclavian artery then courses cranially and to the right, posterior to the esophagus and trachea. AA, Arch of aorta; BT, brachiocephalic trunk; RCC, right common carotid artery; LCC, left common carotid artery; LV, left vertebral artery.
  870. Coarctation of Aorta
  871. Double Pharyngeal Arch Artery
  872. Fetal And Neonatal Circulation
  873. Fetal Circulation
  874. Transitional Neonatal Circulation
  875. FIGURE 13-46 Fetal circulation. The colors indicate the oxygen saturation of the blood, and the arrows show the course of the blood from the placenta to the heart. The organs are not drawn to scale. A small amount of highly oxygenated blood from the inferior vena cava remains in the right atrium and mixes with poorly oxygenated blood from the superior vena cava. The medium oxygenated blood then passes into the right ventricle. Observe that three shunts permit most of the blood to bypass the liver and lungs: (1) ductus venosus, (2) oval foramen, and (3) ductus arteriosus. The poorly oxygenated blood returns to the placenta for oxygenation and nutrients through the umbilical arteries.
  876. FIGURE 13-47 Neonatal circulation. The adult derivatives of the fetal vessels and structures that become nonfunctional at birth are shown. The arrows indicate the course of the blood in the infant. The organs are not drawn to scale. After birth, the three shunts that shortcircuited the blood during fetal life cease to function, and the pulmonary and systemic circulations become separated.
  877. FIGURE 13-48 A, Schematic illustration of the course of the umbilical vein from the umbilical cord to the liver. B, Ultrasound scan showing the umbilical cord and the course of its vessels in the embryo, b, bladder; c, umbilical cord; DV, ductus venosus; UV, umbilical vein; UA, umbilical artery. C, Schematic presentation of the relationship among the ductus venosus, umbilical vein, hepatic veins, and inferior vena cava. The oxygenated blood is coded with red.
  878. FIGURE 13-49 Dissection of the visceral surface of the fetal liver. Approximately 50% of umbilical venous blood bypasses the liver and joins the inferior vena cava through the ductus venosus.
  879. FIGURE 13-50 Schematic diagram of blood flow through the fetal atria illustrating how the crista dividens (lower edge of septum secundum) separates the blood coming from the inferior vena cava into two streams. The larger stream passes through the oval foramen into the left atrium, where it mixes with the small amount of poorly oxygenated blood coming from the lungs through the pulmonary veins. The smaller stream of blood from the inferior vena cava remains in the right atrium and mixes with poorly oxygenated blood from the superior vena cava and coronary sinus.
  880. Derivatives of Fetal Vessels and Structures
  881. Umbilical Vein and Round Ligament of Liver
  882. Ductus Venosus and Ligamentum Venosum
  883. Umbilical Arteries and Abdominal Ligaments
  884. Oval Foramen and Oval Fossa
  885. Ductus Arteriosus and Ligamentum Arteriosum
  886. FIGURE 13-51 Dissection of the visceral surface of an adult liver. Note that the umbilical vein is represented by the round ligament of the liver and the ductus venosus by the ligamentum venosum.
  887. FIGURE 13-52 Dissection of the right atrial aspect of the interatrial septum of an adult heart. Observe the oval fossa and the border of the oval fossa. The floor of the oval fossa is formed by the septum primum, whereas the border of the fossa is formed by the free edge of the septum secundum. Aeration of the lungs at birth is associated with a dramatic decrease in pulmonary vascular resistance and a marked increase in pulmonary flow. Because of the increased pulmonary blood flow, the pressure in the left atrium is increased above that in the right atrium. This increased left atrial pressure closes the oval foramen by pressing the valve of the oval foramen against the septum secundum. This forms the oval fossa.
  888. FIGURE 13-53 Closure of the ductus arteriosus (DA). A, The DA of a neonate. B, Abnormal patent DA in a 6-month-old infant. C, The ligamentum arteriosum in a 6-month-old infant.
  889. FIGURE 13-54 Development of the lymphatic system. A, Left side of a -week embryo showing the primary lymph sacs. B, Ventral view of the lymphatic system at 9 weeks showing the paired thoracic ducts. C, Later in the fetal period, illustrating formation of the thoracic duct and right lymphatic duct.
  890. Patent Ductus Arteriosus
  891. Development Of Lymphatic System
  892. Development of Lymph Sacs and Lymphatic Ducts
  893. Development of Thoracic Duct
  894. Development of Lymph Nodes
  895. Development of Lymphocytes
  896. Development of Spleen and Tonsils
  897. Anomalies of Lymphatic System
  898. Summary Of Cardiovascular System
  899. FIGURE 13-55 Cystic hygroma. A, Transverse axial sonogram of the neck of a fetus with a large cystic hygroma. B, Photograph of a neck dissection. Cystic hygroma was demonstrated from this cross-sectional view of the posterior fetal neck at 18.5 weeks. The lesion was characterized by multiple, septated cystic areas within the mass itself as shown in the pathology specimen. Post, posterior.
  900. Clinically Oriented Problems
  901. Case 13–1
  902. Case 13–2
  903. Case 13–3
  904. Case 13–4
  905. Case 13–5
  906. References and Suggested Reading
  907. Chapter 14 Skeletal System
  908. Development Of Bone And Cartilage
  909. FIGURE 14-1 Illustrations of formation and early differentiation of somites. A, Dorsal view of an embryo of approximately 18 days. B, Transverse section of the embryo shown in A illustrating the paraxial mesoderm from which the somites are derived. C, Transverse section of an embryo of approximately 22 days showing the appearance of the early somites. Note that the neural folds are about to fuse to form the neural tube. D, Transverse section of an embryo of approximately 24 days showing folding of the embryo in the horizontal plane (arrows). The dermomyotome region of the somite gives rise to the dermatome and myotome. E, Transverse section of an embryo of approximately 26 days showing the dermatome, myotome, and sclerotome regions of a somite.
  910. Histogenesis of Cartilage
  911. FIGURE 14-2 Schematic representation of secreted molecules and transcription factors regulating the initial differentiation, proliferation, and terminal differentiation of chondrocytes. From top to bottom: mesenchymal cells (blue), resting and proliferating (nonhypertrophic) chondrocytes (red), and hypertrophic chondrocytes (yellow). Line with arrowheads indicate a positive action, and lines with bars indicate an inhibition.
  912. Histogenesis of Bone
  913. Membranous Ossification
  914. FIGURE 14-3 Light micrograph of membranous ossification (x132). Trabeculae of bone are being formed by osteoblasts lining their surface (arrows). Observe osteocytes trapped in lacunae (arrowheads) and that primordial osteons are beginning to form. The osteons (canals) contain blood capillaries.
  915. Endochondral Ossification
  916. Rickets
  917. Development Of Joints
  918. Fibrous Joints
  919. FIGURE 14-4 A to E, Schematic longitudinal sections of a 5-week embryo, illustrating endochondral ossification in a developing long bone.
  920. FIGURE 14-5 Development of joints during the sixth and seventh weeks. A, Condensed interzonal mesenchyme in the gap between the developing bones. This primordial joint may differentiate into a synovial joint (B), a cartilaginous joint (C), or a fibrous joint (D).
  921. Cartilaginous Joints
  922. Synovial Joints
  923. Development Of Axial Skeleton
  924. Development of Vertebral Column
  925. FIGURE 14-6 A, Transverse section through a 4-week embryo. The arrows indicate the dorsal growth of the neural tube and the simultaneous dorsolateral movement of the somite remnant, leaving behind a trail of sclerotomal cells. B, Diagrammatic frontal section of this embryo showing that the condensation of sclerotomal cells around the notochord consists of a cranial area of loosely packed cells and a caudal area of densely packed cells. C, Transverse section through a 5-week embryo showing the condensation of sclerotomal cells around the notochord and neural tube, which forms a mesenchymal vertebra. D, Diagrammatic frontal section illustrating that the vertebral body forms from the cranial and caudal halves of two successive sclerotomal masses. The intersegmental arteries now cross the bodies of the vertebrae, and the spinal nerves lie between the vertebrae. The notochord is degenerating except in the region of the intervertebral disc, where it forms the nucleus pulposus.
  926. Chordoma
  927. Cartilaginous Stage of Vertebral Development
  928. Bony Stage of Vertebral Development
  929. FIGURE 14-7 Stages of vertebral development. A, Mesenchymal vertebra at 5 weeks. B, Chondrification centers in a mesenchymal vertebra at 6 weeks. The neural arch is the primordium of the vertebral arch. C, Primary ossification centers in a cartilaginous vertebra at 7 weeks. D, Thoracic vertebra at birth consisting of three bony parts: vertebral arch, body of vertebra and transverse processes. Note the cartilage between the halves of the vertebral arch and between the arch and the centrum (neurocentral joint). E and F, Two views of a typical thoracic vertebra at puberty showing the location of the secondary centers of ossification.
  930. Variation in the Number of Vertebrae
  931. Development of Ribs
  932. Development of Sternum
  933. Development of Cranium
  934. Cartilaginous Neurocranium
  935. Membranous Neurocranium
  936. Cartilaginous Viscerocranium
  937. Membranous Viscerocranium
  938. Cranium of Neonate
  939. FIGURE 14-8 Stages in the development of the cranium. A to C, Views of the base of the developing cranium (viewed superiorly). D, A lateral view. A, At 6 weeks showing the various cartilages that will fuse to form the chondrocranium. B, At 7 weeks, after fusion of some of the paired cartilages. C, At 12 weeks showing the cartilaginous base of the cranium formed by the fusion of various cartilages. D, At 20 weeks indicating the derivation of the bones of the fetal cranium.
  940. Postnatal Growth of Cranium
  941. FIGURE 14-9 A fetal cranium showing the bones, fontanelles, and sutures. A, Lateral view. B, Superior view. The posterior and anterolateral fontanelles disappear because of growth of surrounding bones, within 2 or 3 months after birth, but they remain as sutures for several years. The posterolateral fontanelles disappear in a similar manner by the end of the first year and the anterior fontanelle by the end of the second year. The halves of the frontal bone normally begin to fuse during the second year, and the frontal suture is usually obliterated by the eighth year. The other sutures disappear during adult life, but the times when the sutures close are subject to wide variations. C, Three-dimensional ultrasound rendering of the fetal head at 22 weeks. Note the anterior fontanelle (*) and the frontal suture (arrow). The coronal and sagittal sutures are also shown.
  942. Klippel-Feil Syndrome (Brevicollis)
  943. Spina Bifida
  944. Accessory Ribs
  945. Fused Ribs
  946. FIGURE 14-10 Vertebral and rib abnormalities. A, Cervical and forked ribs. Observe that the left cervical rib has a fibrous band that passes posterior to the subclavian vessels and attaches to the manubrium of the sternum. B, Anterior view of the vertebral column showing a hemivertebra. The right half of the third thoracic vertebra is absent. Note the associated lateral curvature (scoliosis) of the vertebral column. C, Radiograph of a child with the kyphoscoliotic deformity of the lumbar region of the vertebral column showing multiple anomalies of the vertebrae and ribs. Note the fused ribs (arrow).
  947. Hemivertebra
  948. Rachischisis
  949. Anomalies of Sternum
  950. Cranial Birth Defects
  951. FIGURE 14-11 A, A second-trimester fetus with holoacrania (absence of the cranium, i.e., acrania). Note the cyst-like structure surrounding the intact fetal brain. B, Lateral view of a newborn infant with acrania and meroencephaly (partial absence of the brain), as well as rachischisis, which are extensive clefts in vertebral arches of the vertebral column (not clearly visible).
  952. FIGURE 14-12 Craniosynostosis. A and B, An infant with scaphocephaly. This condition results from premature closure (synostosis) of the sagittal suture. Note the elongated, wedge-shaped cranium seen from above (A) and the side (B). C, An infant with bilateral premature closure of the coronal suture (brachycephaly). Note the high, markedly elevated forehead. D, An infant with premature closure of the frontal suture (trigonocephaly). Note the hypertelorism (abnormal distance between the eyes) and prominent midline ridging of the forehead.
  953. Acrania
  954. Craniosynostosis
  955. Microcephaly
  956. Anomalies at Craniovertebral Junction
  957. Development Of Appendicular Skeleton
  958. Bone Age
  959. FIGURE 14-13 A, Photograph of an embryo at approximately 28 days showing the early appearance of the limb buds. B, Longitudinal section through an upper limb bud showing the apical ectodermal ridge, which has an inductive influence on the mesenchyme in the limb bud. This ridge promotes growth of the mesenchyme and appears to give it the ability to form specific cartilaginous elements. C, Similar sketch of an upper limb bud at approximately 33 days showing the mesenchymal primordia of the forearm bones. The digital rays are mesenchymal condensations that undergo chondrification and ossification to form the bones of the hand. D, Upper limb at 6 weeks showing the cartilage models of the bones. E, Later in the sixth week showing the completed cartilaginous models of the bones of the upper limb.
  960. Generalized Skeletal Malformations
  961. FIGURE 14-14 Alizarin-stained and cleared human fetuses. A, A 12-week fetus. Observe the degree of progression of ossification from the primary centers of ossification, which is endochondral in the appendicular and axial parts of the skeleton except for most of the cranial bones (i.e., those that form the neurocranium). Observe that the carpus and tarsus are wholly cartilaginous at this stage, as are the epiphyses of all long bones. B and C, An approximately 20-week fetus.
  962. FIGURE 14-15 Radiograph of the skeletal system of a 2-year-old child with achondroplasia. Note the shortening of the humerus and femur with metaphysis flaring.
  963. Hyperpituitarism
  964. Hypothyroidism and Cretinism
  965. Summary Of Skeletal System
  966. Clinically Oriented Problems
  967. Case 14–1
  968. Case 14–2
  969. Case 14–3
  970. Case 14–4
  971. Case 14–5
  972. References and Suggested Reading
  973. Chapter 15 Muscular System
  974. Development of Skeletal Muscle
  975. FIGURE 15-1 A, Sketch of an embryo (approximately 41 days) showing the myotomes and developing muscular system. B, Transverse section of the embryo illustrating the epaxial and hypaxial derivatives of a myotome. C, Similar section of a 7-week embryo showing the muscle layers formed from the myotomes.
  976. FIGURE 15-2 A model for molecular interactions during myogenesis. Shh and Wnts, produced by the neural tube (NT) and notochord (NC), induce Pax-3 and Myf-5 in the somites. Either of them can activate the initiation of MyoD transcription and myogenesis. Surface ectoderm (E) is also capable of inducing Myf-5 and MyoD. In addition, Pax-3 regulates the expression of c-met, necessary for the migratory ability of myogenic precursor cells, that also express En-1, Sim-1, lbx-1, and 26M15. DM, dermamyotome; S, sclerotome.
  977. Myotomes
  978. FIGURE 15-3 Embryonic structures and myogenesis. The current view suggests that the dorsal neural tube (NT) and the overlying non-neural ectoderm (E) are sources of signaling molecules belonging to the family of Wnt-secreted proteins and bone morphogenetic protein (BMP)-4, whereas the notochord (NC) and the ventral neural tube (green) are sources of the Shh. They positively regulate the onset of myogenesis and the induction of the myotome. By contrast, the lateral plate mesoderm (LPM) produces BMP-4 and FGF5 (fibroblast growth factor 5), negatively regulating muscle terminal differentiation in the lateral part of the myotome lineage. Response to the BMP-4 signal may be mediated by its binding proteins noggin and follistatin. DM, dermamyotome; S, sclerotome.
  979. FIGURE 15-4 Illustrations of the developing muscular system. A, A 6-week embryo showing the myotome regions of the somites that give rise to skeletal muscles. B, An 8-week embryo showing the developing trunk and limb musculature.
  980. Pharyngeal Arch Muscles
  981. Ocular Muscles
  982. Tongue Muscles
  983. Limb Muscles
  984. Development of Smooth Muscle
  985. Development of Cardiac Muscle
  986. FIGURE 15-5 The thorax of an infant with congenital absence of the left pectoralis major muscle. Note the absence of the anterior axillary fold on the left and the low location of the left nipple.
  987. Anomalies of Muscles
  988. Arthrogryposis
  989. Variations in Muscles
  990. Congenital Torticollis
  991. FIGURE 15-6 Neonate with multiple joint contractures: arthrogryposis. Infants with this syndrome have stiffness of the joints associated with hypoplasia of the associated muscles.
  992. FIGURE 15-7 The head and neck of a 12-year-old boy with congenital torticollis (wryneck). Shortening of the right sternocleidomastoid muscle has caused tilting of the head to the right and turning of the chin to the left. There is also asymmetrical development of the face and cranium.
  993. Abdominal Muscle Deficiency
  994. Accessory Muscles
  995. Summary of Muscular System
  996. Clinically Oriented Problems
  997. Case 15–1
  998. Case 15–2
  999. Case 15–3
  1000. Case 15–4
  1001. References and Suggested Reading
  1002. Chapter 16 Development of Limbs
  1003. Early Stages of Limb Development
  1004. FIGURE 16-1 Drawings of human embryos showing development of the limbs. A, Lateral view of an embryo at approximately 28 days. The upper limb bud appears as a swelling or bulge on the ventrolateral body wall. The lower limb bud is smaller than the upper limb bud. B, Lateral view of an embryo at approximately 32 days. The upper limb buds are paddle-shaped and the lower limb buds are flipper-like.
  1005. FIGURE 16-2 A, Oblique section of an embryo at approximately 28 days. Observe the paddle-like upper limb bud lateral to the embryonic heart and AER. B, Signaling pathways regulating the elongation and segmentation of the digit ray. AER-Fgf signal (red) maintains a small population of subridge undifferentiated mesenchymal cells, which are being actively incorporated into the digital condensation (blue). At the presumptive joint site, the newly differentiated chondrogenic cells de-differentiate into the interzone fate under the regulation of multiple signaling pathways. Wnts promote chondrocyte dedifferentiation through canonical Wnt signaling. Ihh signals to the interzone region through the localized Gli2/Gli3 expression. TGFs signals to the interzone cells through the type II receptor. Gdf5 regulates the progression of the joint and skeletogenesis of the digit elements.
  1006. FIGURE 16-3 Illustrations of development of the limbs (32–56 days). The upper limbs develop earlier than the lower limbs.
  1007. FIGURE 16-4 Illustrations of development of the hands and feet between the fourth and eighth weeks. The early stages of limb development are alike, except that development of the hands precedes that of the feet by a day or two. A, At 27 days. B, At 32 days. C, At 41 days. D, At 46 days. E, At 50 days. F, At 52 days. G, At 28 days. H, At 36 days. I, At 46 days. J, At 49 days. K, At 52 days. L, At 56 days. The arrows in D and J indicate the tissue breakdown process (apoptosis) that separates the fingers and toes.
  1008. Final Stages of Limb Development
  1009. Cutaneous Innervation of Limbs
  1010. FIGURE 16-5 Scanning electron micrographs showing dorsal (A) and plantar (B) views of the right foot of an embryo at approximately 48 days. The toe buds (arrowheads in A) and the heel cushion and metatarsal tactile elevation (asterisks in B) have just appeared. Dorsal (C) and distal (D) views of the right foot of embryos at approximately 55 days. The tips of the toes are separated and interdigital degeneration has begun. Note the dorsiflexion of the metatarsus and toes (C) as well as the thickened heel cushion (D).
  1011. FIGURE 16-6 A and B, Scanning electron micrographs. A, Dorsal view of the right foot of an embryo at 8 weeks. B, Plantar view of the left foot of this embryo. Although supinated, dorsiflexion of the foot is distinct. C and D, Paraffin sections of the tarsus and metatarsus of a young fetus, stained with hematoxylin and eosin: 1–5, metatarsal cartilages; 6, cubital cartilage; 7, calcaneus. The separation of the interosseous muscles (im) and short flexor muscles of the big toe (sfh) is clearly seen. The plantar crossing (cr) of the tendons of the long flexors of the digits and hallux (great toe) is shown in D.
  1012. FIGURE 16-7 Schematic longitudinal sections of the upper limb of a human embryo, showing the development of cartilaginous bones. A, At 28 days. B, At 44 days. C, At 48 days. D, At 56 days.
  1013. FIGURE 16-8 Drawings of lateral views of embryos. A, At approximately 52 days. The fingers are separated and the toes are beginning to separate. Note that the feet are fan shaped. B, At approximately 56 days. All regions of the limbs are apparent and the digits of the hands and feet are separated.
  1014. FIGURE 16-9 Illustrations of positional changes of the developing limbs of embryos. A, At approximately 48 days, showing the limbs extending ventrally and the hand plates and foot plates facing each other. B, At approximately 51 days, showing the upper limbs bent at the elbows and the hands curved over the thorax. C, At approximately 54 days, showing the soles of the feet facing medially. D, At approximately 56 days (end of embryonic stage). Note that the elbows now point caudally and the knees cranially.
  1015. FIGURE 16-10 Illustrations of development of the dermatomal patterns of the limbs. The axial lines indicate where there is no sensory overlap. A and D, Ventral aspect of the limb buds early in the fifth week. At this stage, the dermatomal patterns show the primordial segmental arrangement. B and E, Similar views later in the fifth week showing the modified arrangement of dermatomes. C and F, The dermatomal patterns in the adult upper and lower limbs. The primordial dermatomal pattern has disappeared, but an orderly sequence of dermatomes can still be recognized. F, Note that most of the original ventral surface of the lower limb lies on the back of the adult limb. This results from the medial rotation of the lower limb that occurs toward the end of the embryonic period. In the upper limb, the ventral axial line extends along the anterior surface of the arm and forearm. In the lower limb, the ventral axial line extends along the medial side of the thigh and knee to the posteromedial aspect of the leg to the heel.
  1016. Blood Supply of Limbs
  1017. FIGURE 16-11 Development of limb arteries. A, Sketch of the primordial cardiovascular system in an embryo at approximately 26 days. B, Development of arteries in the upper limb. C, Development of arteries in the lower limb.
  1018. Birth Defects of Limbs
  1019. FIGURE 16-12 Birth defects of limbs caused by maternal ingestion of thalidomide. A, Quadruple amelia: absence of upper and lower limbs. B, Meromelia of the upper limbs; the limbs are represented by rudimentary stumps. C, Meromelia with the rudimentary upper limbs attached directly to the trunk.
  1020. Limb Anomalies
  1021. Causes of Limb Anomalies
  1022. Bifurcate Hand and Cleft Foot or Split Hand/Foot Malformations
  1023. Congenital Absence of Radius
  1024. Brachydactyly
  1025. Polydactyly
  1026. FIGURE 16-13 Various types of birth defects. A, Female neonate with amelia, complete absence of the upper limbs. B, Radiograph of a female fetus showing absence of the right fibula. Note also that the right leg is shorter and the femur and tibia are bowed and hypoplastic (underdevelopment of tissue of the limb). C, Radiograph showing partial absence and fusion of the lower ends of the tibia and fibula in a 5-year-old child. D, Absence of the central digits of the hands, resulting in a defect called bifurcate (forked) hand or split hand. E, Absence of the second to fourth toes, resulting in a bifurcate hand or split foot.
  1027. FIGURE 16-14 Types of digital birth defects. Polydactyly (more than five digits, fingers or toes, on the hands (A) or (B) feet). Syndactyly (webbing or fusion) of the fingers (C) or toes (D).
  1028. Syndactyly
  1029. Congenital Clubfoot
  1030. Developmental Dysplasia of the Hip
  1031. FIGURE 16-15 Neonate with bilateral talipes equinovarus (clubfeet). Observe the hyperextension and incurving of the feet.
  1032. Summary of Limb Development
  1033. Clinically Oriented Problems
  1034. Case 16–1
  1035. Case 16–2
  1036. Case 16–3
  1037. Case 16–4
  1038. References and Suggested Reading
  1039. Chapter 17 Nervous System
  1040. Development of Nervous System
  1041. FIGURE 17-1 Illustrations of the neural plate and folding of it to form the neural tube. A, Dorsal view of an embryo of approximately 17 days, exposed by removing the amnion. B, Transverse section of the embryo showing the neural plate and early development of the neural groove and neural folds. C, Dorsal view of an embryo of approximately 22 days. The neural folds have fused opposite the fourth to sixth somites, but are spread apart at both ends. D to F, Transverse sections of this embryo at the levels shown in C illustrating formation of the neural tube and its detachment from the surface ectoderm. Note that some neuroectodermal cells are not included in the neural tube, but remain between it and the surface ectoderm as the neural crest.
  1042. FIGURE 17-2 Morphogens and transcription factors specify the fate of progenitors in the ventral neural tube. A, Sonic hedgehog (Shh) is secreted by the notochord (NC) and the floor plate (FP) of the neural tube in a ventral to dorsal gradient. Similarly, bone morphogenetic proteins (BMPs), members of the transforming growth factor β superfamily, are secreted by the roof plate (RP) of the neural tube and the overlying epidermis, in a dorsal to ventral gradient. These opposing morphogen gradients determine dorsal-ventral cell fates. B, Shh concentration gradients define the ventral expression domains of class I (repressed) and class II (activated) homeobox transcription factors. Reciprocal negative interactions assist to establish boundaries of gene expression in the embryonic ventral spinal cord. P, progenitor; MN, motor neuron; V, ventral interneuron.
  1043. FIGURE 17-3 A, Dorsal view of an embryo of approximately 23 days showing fusion of the neural folds, which forms the neural tube. B, Lateral view of an embryo of approximately 24 days showing the forebrain prominence and closing of the rostral neuropore. C, Diagrammatic sagittal section of the embryo showing the transitory communication of the neural canal with the amniotic cavity (arrows). D, Lateral view of an embryo of approximately 27 days. Note that the neuropores shown in B are closed.
  1044. Nonclosure of Neural Tube
  1045. Development of Spinal Cord
  1046. FIGURE 17-4 A, Schematic lateral view of an embryo of approximately 28 days showing the three primary brain vesicles: forebrain, midbrain, and hindbrain. Two flexures demarcate the primary divisions of the brain. B, Transverse section of the embryo showing the neural tube that will develop into the spinal cord in this region. The spinal ganglia derived from the neural crest are also shown. C, Schematic lateral view of the central nervous system (CNS) of a 6-week embryo showing the secondary brain vesicles and pontine flexure, which occurs as the brain grows rapidly.
  1047. FIGURE 17-5 Illustrations of the development of the spinal cord. A, Transverse section of the neural tube of an embryo of approximately 23 days. B and C, Similar sections at 6 and 9 weeks, respectively. D, Section of the wall of the neural tube shown in A. E, Section of the wall of the developing spinal cord showing its three zones. In A to C, note that the neural canal of the neural tube is converted into the central canal of the spinal cord.
  1048. Development of Spinal Ganglia
  1049. Development of Meninges
  1050. FIGURE 17-6 Histogenesis of cells in the central nervous system. After further development, the multipolar neuroblast (lower left) becomes a nerve cell or neuron. Neuroepithelial cells give rise to all neurons and macroglial cells. Microglial cells are derived from mesenchymal cells that invade the developing nervous system with the blood vessels.
  1051. Positional Changes of Spinal Cord
  1052. FIGURE 17-7 Transverse section of an embryo (x100) at Carnegie stage 16 at approximately 40 days. The ventral root of the spinal nerve is composed of nerve fibers arising from neuroblasts in the basal plate (developing ventral horn of spinal cord), whereas the dorsal root is formed by nerve processes arising from neuroblasts in the spinal ganglion.
  1053. FIGURE 17-8 Diagrams showing some derivatives of the neural crest. Neural crest cells also differentiate into the cells in the afferent ganglia of cranial nerves and many other structures (see Chapter 5). The formation of a spinal nerve is also illustrated.
  1054. FIGURE 17-9 A to D, Diagrams of successive stages in the differentiation of a neural crest cell into a unipolar afferent neuron in a spinal ganglion.
  1055. FIGURE 17-10 Diagrams showing the position of the caudal end of the spinal cord in relation to the vertebral column and meninges at various stages of development. The increasing inclination of the root of the first sacral nerve is also illustrated. A, At 8 weeks. B, At 24 weeks. C, Neonate. D, Adult.
  1056. Myelination of Nerve Fibers
  1057. Birth Defects of Spinal Cord
  1058. FIGURE 17-11 Diagrammatic sketches illustrating myelination of nerve fibers. A to E, Successive stages in the myelination of an axon of a peripheral nerve fiber by the neurolemma (sheath of Schwann). The axon first indents the cell; the cell then rotates around the axon as the mesaxon (site of invagination) elongates. The cytoplasm between the layers of the cell membrane gradually condenses. Cytoplasm remains on the inside of the sheath between the myelin and axon. F to H, Successive stages in the myelination of a nerve fiber in the central nervous system by an oligodendrocyte. A process of the neuroglial cell wraps itself around an axon, and the intervening layers of cytoplasm move to the body of the cell.
  1059. FIGURE 17-12 Diagrammatic sketches illustrating various types of spina bifida and the associated defects of the vertebral arches (one or more), spinal cord, and meninges. A, Spina bifida occulta. Observe the unfused vertebral arch. B, Spina bifida with meningocele. C, Spina bifida with meningomyelocele. D, Spina bifida with myeloschisis. The defects illustrated in B to D are referred to collectively as spina bifida cystica because of the cyst-like sac or cyst associated with them.
  1060. FIGURE 17-13 A fetus at 20 weeks with severe neural tube defects, including acrania, cerebral regression (meroencephaly), iniencephaly (enlargement of foramen magnum), and a sacral dimple (arrow).
  1061. FIGURE 17-14 A female child with a hairy patch in the lumbosacral region indicating the site of a spina bifida occulta.
  1062. Dermal Sinus
  1063. Spina Bifida Occulta
  1064. Spina Bifida Cystica
  1065. FIGURE 17-15 Infants with spina bifida cystica. A, Spina bifida with meningomyelocele in the lumbar region. B, Spina bifida with myeloschisis in the lumbar region. Note the nerve involvement has affected the lower limbs.
  1066. Menigomyelocele
  1067. Myeloschisis
  1068. Etiology of Neural Tube Defects
  1069. FIGURE 17-16 A 19-week female fetus showing an open spinal defect in the lumbosacral region (spina bifida with myeloschisis).
  1070. FIGURE 17-17 Schematic illustrations showing the embryologic basis of neural tube defects. Meroencephaly, partial absence of brain, results from defective closure of the rostral neuropore, and meningomyelocele results from defective closure of the caudal neuropore.
  1071. Development of Brain
  1072. Brain Flexures
  1073. FIGURE 17-18 Diagrammatic sketches of the brain vesicles indicating the adult derivatives of their walls and cavities. The rostral part of the third ventricle (*) forms from the cavity of the telencephalon; most of this ventricle is derived from the cavity of the diencephalon.
  1074. Hindbrain
  1075. Myelencephalon
  1076. FIGURE 17-19 A, Sketch of the developing brain at the end of the fifth week showing the three primary divisions of the brain and the brain flexures. B, Transverse section of the caudal part of the myelencephalon (developing closed part of the medulla). C and D, Similar sections of the rostral part of the myelencephalon (developing open part of the medulla) showing the position and successive stages of differentiation of the alar and basal plates. The arrows in C show the pathway taken by neuroblasts from the alar plates to form the olivary nuclei.
  1077. Metencephalon
  1078. FIGURE 17-20 A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the metencephalon (developing pons and cerebellum) showing the derivatives of the alar and basal plates. C and D, Sagittal sections of the hindbrain at 6 and 17 weeks, respectively, showing successive stages in the development of the pons and cerebellum.
  1079. Choroid Plexuses and Cerebrospinal Fluid
  1080. Midbrain
  1081. FIGURE 17-21 A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the developing midbrain showing the early migration of cells from the basal and alar plates. C, Sketch of the developing brain at 11 weeks. D and E, Transverse sections of the developing midbrain at the level of the inferior and superior colliculi, respectively. CN, cranial nerve.
  1082. Forebrain
  1083. FIGURE 17-22 A, External view of the brain at the end of the fifth week. B, Similar view at 7 weeks. C, Median section of this brain showing the medial surface of the forebrain and midbrain. D, Similar section at 8 weeks. E, Transverse section of the diencephalon showing the epithalamus dorsally, the thalamus laterally, and the hypothalamus ventrally.
  1084. Diencephalon
  1085. FIGURE 17-23 Diagrammatic sketches illustrating the development of the pituitary gland. A, Sagittal section of the cranial end of an embryo at approximately 36 days showing the hypophysial diverticulum, an upgrowth from the stomodeum, and the neurohypophysial diverticulum, a downgrowth from the forebrain. B to D, Successive stages of the developing pituitary gland. By 8 weeks, the diverticulum loses its connection with the oral cavity and is in close contact with the infundibulum and the posterior lobe (neurohypophysis) of the pituitary gland. E and F, Later stages showing proliferation of the anterior wall of the hypophysial diverticulum to form the anterior lobe (adenohypophysis) of the pituitary gland.
  1086. Table 17-1 Derivation and Terminology of Pituitary Gland
  1087. Pharyngeal Hypophysis and Craniopharyngioma
  1088. Telencephalon
  1089. FIGURE 17-24 Sagittal magnetic resonance image of a 4-year-old boy who presented with a headache and optic atrophy. A large mass (4 cm) occupies an enlarged sella turcica, expanding inferiorly into the sphenoid bone and superiorly into the suprasellar cistern. A craniopharyngioma was confirmed by surgery. The inferior half of the mass is solid and appears dark, whereas the superior half is cystic and appears brighter.
  1090. FIGURE 17-25 Photomicrograph of a transverse section through the diencephalon and cerebral vesicles of a human embryo (approximately 50 days) at the level of the interventricular foramina (×20). The choroid fissure is located at the junction of the choroid plexus and the medial wall of the lateral ventricle.
  1091. FIGURE 17-26 A, Sketch of the dorsal surface of the forebrain indicating how the ependymal roof of the diencephalon is carried out to the dorsomedial surface of the cerebral hemispheres. B, Diagrammatic section of the forebrain showing how the developing cerebral hemispheres grow from the lateral walls of the forebrain and expand in all directions until they cover the diencephalon. The arrows indicate some directions in which the hemispheres expand. The rostral wall of the forebrain, the lamina terminalis, is very thin. C, Sketch of the forebrain showing how the ependymal roof is finally carried into the temporal lobes as a result of the C-shaped growth pattern of the cerebral hemispheres.
  1092. Cerebral Commissures
  1093. FIGURE 17-27 A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.
  1094. FIGURE 17-28 Schematic diagrams of the medial surface of the developing right cerebral hemisphere, showing the development of the lateral ventricle, choroid fissure, and corpus striatum. A, At 13 weeks. B, At 21 weeks. C, At 32 weeks.
  1095. Birth Defects of Brain
  1096. Encephalocele
  1097. FIGURE 17-29 Sketches of lateral views of the left cerebral hemisphere, diencephalon, and brainstem, showing successive stages in the development of the sulci and gyri in the cerebral cortex. Note the gradual narrowing of the lateral sulcus and burying of the insula (island), an area of cerebral cortex that is concealed from surface view. Note that the surface of the cerebral hemispheres grows rapidly during the fetal period, forming many gyri (convolutions), which are separated by many sulci (grooves). A, At 14 weeks. B, At 26 weeks. C, At 30 weeks. D, At 38 weeks. E, Magnetic resonance image (MRI) of a pregnant woman showing a mature fetus. Observe the brain and spinal cord. Inset, The smooth lateral (top) and medial (bottom) surfaces of a human fetal brain (14 weeks).
  1098. FIGURE 17-30 A, Lateral view of the brain of a stillborn fetus (25 weeks). B, The medial (top) and lateral (bottom) surfaces of the fetal brain (week 25). C, The lateral (top) and medial (bottom) surfaces of the fetal brain (week 38). Note that as the brain enlarges, the gyral pattern of the cerebral hemispheres becomes more complex; compare with Figure 17-29.
  1099. FIGURE 17-31 Schematic drawings illustrating encephalocele (cranium bifidum) and various types of herniation of the brain and/or meninges. A, Sketch of the head of a newborn infant with a large protrusion from the occipital region of the cranium. The upper red circle indicates a cranial defect at the posterior fontanelle (membranous interval between cranial bones). The lower red circle indicates a cranial defect near the foramen magnum. B, Meningocele consisting of a protrusion of the cranial meninges that is filled with cerebrospinal fluid (CSF). C, Meningoencephalocele consisting of a protrusion of part of the cerebellum that is covered by meninges and skin. D, Meningohydroencephalocele consisting of a protrusion of part of the occipital lobe that contains part of the posterior horn of a lateral ventricle.
  1100. FIGURE 17-32 A, Focal heterotopic cerebral cortex. Magnetic resonance image of a 19-year-old woman with seizures, showing a focal heterotopic cortex of the right parietal lobe, indenting the right lateral ventricle; note the lack of organized cortex at the overlying surface of the brain. Heterotopic cortex is the result of an arrest of centrifugal migration of neuroblasts along the radial processes of glial cells. B, A coronal section of an adult brain with periventricular heterotopia (arrow) in the parietal cerebrum. The lobulated gray matter structures along the ventricle represent cells that failed to migrate but nevertheless differentiated into neurons.
  1101. FIGURE 17-33 An infant with a large meningoencephalocele in the occipital area.
  1102. Meroencephaly
  1103. FIGURE 17-34 Magnetic resonance images (MRIs) of a 1-day-old infant, showing a menigocele. A, Sagittal MRI taken so that the cerebrospinal fluid (CSF) is bright. The image is blurred because of movement of the infant. B, Axial image located at the cranial defect near the foramen magnum and taken so that CSF appears dark.
  1104. FIGURE 17-35 A, Sonogram of a normal fetus at 12 weeks (left) and a fetus at 14 weeks, showing acrania and meroencephaly (right). B, Magnetic resonance image (MRI) of diamniotic-monochorionic twins, one with meroencephaly. Note the absent calvaria (white arrow) of the abnormal twin and the amnion of the normal twin (black arrow).
  1105. Microcephaly
  1106. FIGURE 17-36 An infant with microcephaly showing the typical normal-sized face and small neurocranium. Usually this defect is associated with mental deficiency.
  1107. Agenesis of Corpus Callosum
  1108. Hydrocephalus
  1109. FIGURE 17-37 A, Sagittal magnetic resonance imaging of the brain of a 22-year-old normal functioning male. There is complete absence of the corpus callosum. B, A coronal slice through a child’s brain showing agenesis of the corpus callosum, which would normally cross the midline to connect the two cerebral hemispheres. Note the thalamus (T) and the downward displacement of the cingulum into the lateral and third ventricles (arrow).
  1110. Holoprosencephaly
  1111. Hydranencephaly
  1112. FIGURE 17-38 A, An infant with hydrocephalus and bilateral cleft palate. B and C, The brain of a 10-year-old child who had developed hydrocephalus in utero as a result of aqueductal stenosis. The thin white matter is well myelinated. A shunt tube meant to treat the hydrocephalus lies in the frontal horn of the ventricle.
  1113. FIGURE 17-39 MRI demonstrating congenital stenosis of the cerebral aqueduct. This sagittal magnetic resonance image shows large lateral and third ventricles. The cerebrospinal fluid (CSF) appears bright in this image. There is also a marked flow void within the cerebral aqueduct.
  1114. FIGURE 17-40 A frontal view of an intact (A) and coronally sectioned (B) fetal brain 21 weeks with holoprosencephaly. This defect results from failure of cleavage of the prosencephalon (rostral neural tube) into right and left cerebral hemispheres, telencephalon and diencephalon, and into olfactory bulbs and optic tracts.
  1115. FIGURE 17-41 MRI of a fetus with massive hydrocephalus or hydrocephaly (*), showing excessive accumulation of CSF. Note the greatly reduced cerebral and displaced cerebral hemispheres and cerebellum.
  1116. FIGURE 17-42 A, An Arnold-Chiari type II malformation in a fetus at 23 weeks. In situ exposure of the hindbrain reveals cerebellar tissue (arrow) well below the foramen magnum. B, MRI of a child with Arnold-Chiari type I malformation. Note the cerebellar tonsils lie inferior to the foramen magnum (red arrow).
  1117. Arnold-Chiari Malformation
  1118. Mental Deficiency
  1119. Development of Peripheral Nervous System
  1120. Spinal Nerves
  1121. Cranial Nerves
  1122. Somatic Efferent Cranial Nerves
  1123. FIGURE 17-43 A, Schematic drawing of a 5-week embryo showing distribution of most of the cranial nerves, especially those supplying the pharyngeal arches. B, Schematic drawing of the head and neck of an adult showing the general distribution of most of the cranial nerves.
  1124. Nerves of Pharyngeal Arches
  1125. Special Sensory Nerves
  1126. Development of Autonomic Nervous System
  1127. Sympathetic Nervous System
  1128. Parasympathetic Nervous System
  1129. Summary of Nervous System
  1130. Clinically Oriented Problems
  1131. Case 17–1
  1132. Case 17–2
  1133. Case 17–3
  1134. Case 17–4
  1135. Case 17–5
  1136. References and Suggested Reading
  1137. Chapter 18 Development of Eyes and Ears
  1138. Development of Eyes and Related Structures
  1139. FIGURE 18-1 Illustrations of the early stages of eye development. A, Dorsal view of the cranial end of an embryo at approximately 22 days, showing the optic grooves, the first indication of eye development. B, Transverse section of a neural fold showing the optic groove in it. C, Schematic drawing of the forebrain of an embryo at approximately 28 days, showing its covering layers of mesenchyme and surface ectoderm. D, F, and H, Schematic sections of the developing eye, illustrating successive stages in the development of the optic cup and lens vesicle. E, Lateral view of the brain of an embryo at approximately 32 days, showing the external appearance of the optic cup. G, Transverse section of the optic stalk, showing the retinal fissure and its contents. Note that the edges of the retinal fissure are growing together, thereby completing the optic cup and enclosing the central artery and vein of the retina in the optic stalk and cup.
  1140. FIGURE 18-2 Photomicrograph of a sagittal section of the eye of an embryo (x200) at approximately 32 days. Observe the primordium of the lens (invaginated lens placode), the walls of the optic cup (primordium of retina), and the optic stalk (primordium of optic nerve).
  1141. Development of Retina
  1142. FIGURE 18-3 Illustrations of the closure of the retinal fissure and formation of the optic nerve. A, C, and E, Views of the inferior surface of the optic cup and stalk, showing progressive stages in the closure of the retinal fissure. C1, Schematic sketch of a longitudinal section of a part of the optic cup and stalk, showing the optic disc and axons of ganglion cells of the retina growing through the optic stalk to the brain. B, D, and F, Transverse sections of the optic stalk showing successive stages in closure of the retinal fissure and formation of the optic nerve. Note that the lumen of the optic stalk is gradually obliterated as axons of ganglion cells accumulate in the inner layer of the optic stalk as the optic nerve forms.
  1143. FIGURE 18-4 Photomicrograph of a sagittal section of the eye of an embryo (x100) at approximately 44 days. Observe that it is the posterior wall of the lens vesicle that forms the lens fibers. The anterior wall does not change appreciably as it becomes the anterior lens epithelium.
  1144. Birth Defects of the Eyes
  1145. Coloboma
  1146. Detachment of the Retina
  1147. Cyclopia
  1148. Microphthalmia
  1149. Anophthalmia
  1150. FIGURE 18-5 Coloboma of iris. Observe the defect in the inferior part of the iris.
  1151. FIGURE 18-6 Male neonate with cyclopia (synophthalmia). Cyclopia (fusion of eyes) is a severe, uncommon birth defect of the face and eye, associated with a proboscis that represents the nose. The white substance covering his head is vernix caseosa—a normal fatty protective covering.
  1152. FIGURE 18-7 Photograph of the head of an infant with anophthalmia (congenital absence of most eye tissues) and a single nostril. The eyelids are formed but are mostly fused.
  1153. Development of Ciliary Body
  1154. Development of Iris
  1155. FIGURE 18-8 Sagittal section of part of the developing eye of an embryo (x280) at approximately 56 days. The lens fibers have elongated and obliterated the cavity of the lens vesicle. Note that the inner layer of the optic cup has thickened to form the primordial neural retina, and that the outer layer is heavily pigmented, which is the primordium of the pigment layer of the retina.
  1156. FIGURE 18-9 Diagrammatic drawings of sagittal sections of the eye, showing successive developmental stages of development of the lens, retina, iris, and cornea. A, At 5 weeks. B, At 6 weeks. C, At 20 weeks. D, Neonate. Note that the retina and optic nerve are formed from the optic cup and optic stalk (Fig. 18-1C).
  1157. Color of the Iris
  1158. Congenital Aniridia
  1159. FIGURE 18-10 Photomicrograph of a sagittal section of the eye of an embryo (x50) at approximately 56 days. Observe the developing neural retina and pigment layer of the retina. The intraretinal space disappears when these two layers of the retina fuse.
  1160. Development of Lens
  1161. FIGURE 18-11 Photomicrograph of a portion of the developing eye of an embryo at the end of the embryonic period. Observe that the lens fibers have elongated and obliterated the cavity of the lens vesicle.
  1162. Persistent Pupillary Membrane
  1163. Persistence of Hyaloid Artery
  1164. Congenital Aphakia
  1165. Development of Aqueous Chambers
  1166. FIGURE 18-12 Clouding of the cornea caused by congenital glaucoma. The clouding may also result from infection, trauma, or metabolic disorders.
  1167. FIGURE 18-13 Typical appearance of a child with a congenital cataract that may be caused by the rubella virus. Cardiac defects and deafness are other birth defects common to this infection.
  1168. Congenital Glaucoma
  1169. Congenital Cataracts
  1170. Development of Cornea
  1171. Edema of Optic Disc
  1172. Development of Choroid and Sclera
  1173. Development of Eyelids
  1174. FIGURE 18-14 A child with congenital bilateral ptosis. Drooping of the superior eyelids usually results from abnormal development or failure of development of the levator palpebrae superioris, the muscle that elevates the eyelids. The infant is contracting the frontalis muscle of the forehead in an attempt to raise the eyelids.
  1175. Congenital Ptosis of Eyelid
  1176. Coloboma of Eyelid
  1177. Cryptophthalmos
  1178. Development of Lacrimal Glands
  1179. Development of Ears
  1180. Development of Internal Ear
  1181. FIGURE 18-15 Drawings illustrating early development of the internal ear. A, Dorsal view of an embryo at approximately 22 days, showing the otic placodes. B, D, F, and G, Schematic coronal sections illustrating successive stages in the development of otic vesicles. C and E, Lateral views of the cranial region of embryos, at approximately 24 and 28 days, respectively.
  1182. FIGURE 18-16 Left, Photomicrograph of a transverse section of an embryo (x55) at approximately 26 days. Observe the otic vesicles, the primordia of the membranous labyrinths, which give rise to the internal ears. Right, Higher magnification of the right otic vesicle (x120). Note the ectodermal stalk, which is still attached to the remnant of the otic placode. The otic vesicle will soon lose its connection with the surface ectoderm.
  1183. FIGURE 18-17 Drawings of the otic vesicles showing the development of the membranous and bony labyrinths of the internal ear. A to E, Lateral views showing successive stages in the development of the otic vesicle into the membranous labyrinth from the fifth to eighth weeks. A to D, Diagrammatic sketches illustrating the development of a semicircular duct. F to I, Sections through the cochlear duct showing successive stages in the development of the spiral organ and the perilymphatic space from the 8th to the 20th weeks.
  1184. Development of Middle Ear
  1185. FIGURE 18-18 Schematic drawings illustrating development of the external and middle parts of the ear. Observe the relationship of these parts of the ear to the otic vesicle, the primordium of the internal ear. A, At 4 weeks, illustrating the relation of the otic vesicle to the pharyngeal apparatus. B, At 5 weeks, showing the tubotympanic recess and pharyngeal arch cartilages. C, Later stage, showing the tubotympanic recess (future tympanic cavity and mastoid antrum) beginning to envelop the ossicles. D, Final stage of ear development showing the relationship of the middle ear to the perilymphatic space and the external acoustic meatus. Note that the tympanic membrane develops from three germ layers: surface ectoderm, mesenchyme, and endoderm of the tubotympanic recess.
  1186. Development of External Ear
  1187. FIGURE 18-19 Illustration of the development of the auricle, the part of the external ear that is not within the head. A, At 6 weeks. Note that three auricular hillocks are located on the first pharyngeal arch and three on the second arch. B, Photograph of a 7-week embryo. Note the developing external ear.
  1188. FIGURE 18-20 Low-set slanted ear. This designation is made when the margin of the auricle or helix (arrow) meets the cranium at a level inferior to the horizontal plane through the corner of the eye.
  1189. FIGURE 18-21 A child with a preauricular tag or skin tag.
  1190. FIGURE 18-22 A child with a rudimentary auricle (microtia). She also has several other birth defects.
  1191. FIGURE 18-23 A child with an auricular fistula relating to the first pharyngeal arch. Note the external orifice of the fistula below the auricle and the upward direction of the catheter (in sinus tract) toward the external acoustic meatus.
  1192. FIGURE 18-24 A child with no external acoustic meatus; however, the auricle is normal. Observe the absence of the opening of the external acoustic meatus. A computed tomography scan revealed normal middle and internal ear structures.
  1193. Congenital Deafness
  1194. Auricular Abnormalities
  1195. Auricular Appendages
  1196. Absence of the Auricle
  1197. Microtia
  1198. Preauricular Sinuses and Fistulas
  1199. Atresia of External Acoustic Meatus
  1200. Absence of External Acoustic Meatus
  1201. Congenital Cholesteatoma
  1202. FIGURE 18-25 CT image of a 9-month-old infant with atresia of the external acoustic meatus (external auditory canal) (*). Observe the osseous atresia plate (black arrow) and the middle ear cavity (white arrow).
  1203. Summary of Development of Eyes
  1204. Summary of Development of Ears
  1205. Clinically Oriented Problems
  1206. Case 18–1
  1207. Case 18–2
  1208. Case 18–3
  1209. Case 18–4
  1210. Case 18–5
  1211. References and Suggested Reading
  1212. Chapter 19 Integumentary System
  1213. Development of Skin and Appendages
  1214. FIGURE 19-1 Illustrations of the successive stages of skin development. A, At 4 weeks. B, At 7 weeks. C, At 11 weeks. D, Neonate. Note the melanocytes in the basal layer of the epidermis and the way their processes extend between the epidermal cells to supply them with melanin.
  1215. FIGURE 19-2 Light micrograph of thick skin (x132). Observe the epidermis and dermis as well as the dermal papilla interdigitating with the epidermal ridges.
  1216. Epidermis
  1217. FIGURE 19-3 Drawing of the successive stages in the development of hairs, sebaceous glands, and arrector muscles of hair. Note that the sebaceous gland develops as an outgrowth from the side of the hair follicle.
  1218. Dermis
  1219. Development of Glands
  1220. Sebaceous Glands
  1221. Sweat Glands
  1222. Disorders of Keratinization
  1223. FIGURE 19-4 Illustrations of the successive stages of the development of a sweat gland. A and B, The cellular buds of the glands develop at approximately 20 weeks as a solid growth of epidermal cells into the mesenchyme. C, Its terminal part coils and forms the body of the gland. The central cells degenerate to form the lumen of the gland. D, The peripheral cells differentiate into secretory cells and contractile myoepithelial cells.
  1224. FIGURE 19-5 A, A child with congenital hypertrichosis and hyperpigmentation. Note the excessive hairiness on the shoulders and back. B, A child with severe keratinization of the skin (ichthyosis) from the time of birth.
  1225. Congenital Ectodermal Dysplasia
  1226. Angiomas of Skin
  1227. FIGURE 19-6 Hemangioma (port-wine stain) in an infant.
  1228. Albinism
  1229. Mammary Glands
  1230. FIGURE 19-7 Development of mammary glands. A, Ventral view of an embryo of approximately 28 days showing the mammary crests. B, Similar view at 6 weeks showing the remains of these crests. C, Transverse section of a mammary crest at the site of a developing mammary gland. D to F, Similar sections showing successive stages of breast development between the 12th week and birth.
  1231. FIGURE 19-8 Sketches of progressive stages in the postnatal development of the female breasts. A, Neonate. B, Child. C, Early puberty. D, Late puberty. E, Young adult. F, Pregnant female. Note that the nipple is inverted at birth (A). At puberty (12–15 years), the breasts of females enlarge because of development of the mammary glands and the increased deposition of fat.
  1232. FIGURE 19-9 Female infant with an extra nipple (polythelia) on the left side.
  1233. FIGURE 19-10 A man with polythelia (extra nipples) in the axillary and thigh regions. Insets are enlargements of the nipples (arrowheads). The broken line indicates the original position of the left mammary crests.
  1234. Gynecomastia
  1235. Absence of Nipples (Athelia) or Breasts (Amastia)
  1236. Aplasia of Breast
  1237. Supernumerary Breasts and Nipples
  1238. Inverted Nipples
  1239. Development of Hairs
  1240. FIGURE 19-11 Light micrograph of a longitudinal section of a hair follicle with its hair root (R) and papilla (P) (x132).
  1241. Alopecia
  1242. Hypertrichosis
  1243. Pili Torti
  1244. Development of Nails
  1245. FIGURE 19-12 Successive stages in the development of a fingernail. A, The first indication of a nail is a thickening of the epidermis, the nail field, at the tip of the finger. B, As the nail plate develops, it slowly grows toward the tip of the finger. C, The fingernail reaches the end of the finger by 32 weeks.
  1246. Aplastic Anonychia
  1247. Development of Teeth
  1248. FIGURE 19-13 Sketches of sagittal sections through the developing jaws illustrating early development of the teeth. A, Early in the sixth week, showing the dental laminae. B, Later in the sixth week, showing tooth buds arising from the laminae.
  1249. FIGURE 19-14 Schematic drawings of sagittal sections illustrating successive stages in the development and eruption of an incisor tooth. A, At 6 weeks, showing the dental lamina. B, At 7 weeks, showing the tooth bud developing from the dental lamina. C, At 8 weeks, showing the cap stage of tooth development. D, At 10 weeks, showing the early bell stage of a deciduous tooth and the bud stage of a permanent tooth. E, At 14 weeks, showing the advanced bell stage of tooth development. Note that the connection (dental lamina) of the tooth to the oral epithelium is degenerating. F, At 28 weeks, showing the enamel and dentine layers. G, At 6 months postnatally, showing early stage of tooth eruption. H, At 18 months postnatally, showing a fully erupted deciduous incisor tooth. The permanent incisor tooth now has a well-developed crown. I, Section through a developing tooth showing ameloblasts (enamel producers) and odontoblasts (dentine producers).
  1250. Table 19-1 Order and Usual Time of Eruption of Teeth and Time of Shedding of Deciduous Teeth
  1251. FIGURE 19-15 Photomicrograph of the primordium of a lower incisor tooth. A, A 12-week-old fetus (early bell stage). A cap-like enamel organ is formed and the dental papilla is developing beneath it. B, Primordium of a lower incisor tooth in a 15-week-old fetus (late bell stage). Observe the inner and outer enamel layers, the dental papilla, and bud of the permanent tooth.
  1252. Bud Stage of Tooth Development
  1253. Cap Stage of Tooth Development
  1254. Bell Stage of Tooth Development
  1255. FIGURE 19-16 Photomicrograph of a section of the crown and neck of a tooth (x17). Observe the enamel (E), dentine (D), dental pulp (P), and odontoblasts (O).
  1256. Tooth Eruption
  1257. FIGURE 19-17 Photomicrograph of a section of a lower incisor tooth in a term fetus. The enamel and dentine layers and the pulp are clearly demarcated.
  1258. FIGURE 19-18 A 4-year-old child’s cranium. Bone has been removed from the mandible and maxilla to expose the relationship of the developing permanent teeth to the erupted deciduous teeth.
  1259. FIGURE 19-19 Some common birth defects of teeth. A, Enamel pearl (furcation of a permanent maxillary third molar). B, Gemination and tetracyline staining (maxillary third molar). C, Fusion (permanent mandibular central and lateral incisors). D, Abnormally short root (microdont permanent maxillary central incisor). E, Dens invaginatus (talon cusps on the lingual surface of the permanent maxillary central incisor). F, Taurodont tooth (radiograph of the mesial surface of the permanent maxillary second molar). G, Fusion (primary mandibular central and lateral incisors).
  1260. FIGURE 19-20 More common birth defects of teeth. A, Amelogenesis imperfecta. B, Extra root (mandibular molar). C, Extra root (mandibular canine). D, Accessory root (maxillary lateral incisor). Extra roots present challenges for root canal therapy and extraction. E, Tetracycline staining (root of maxillary third molar). F, A midline supernumerary tooth (M, mesiodens) located near the apex of the central incisor. The prevalence of supernumerary teeth is 1% to 3% in the general population
  1261. Natal Teeth
  1262. Enamel Hypoplasia
  1263. Variations of Tooth Shape
  1264. Numerical Abnormalities
  1265. Dentigerous Cyst
  1266. Amelogenesis Imperfecta
  1267. Dentinogenesis Imperfecta
  1268. FIGURE 19-21 The teeth of a child with dentinogenesis imperfecta.
  1269. Discolored Teeth
  1270. Summary of Integumentary System
  1271. Clinically Oriented Problems
  1272. Case 19–1
  1273. Case 19–2
  1274. Case 19–3
  1275. Case 19–4
  1276. Case 19–5
  1277. References and Suggested Reading
  1278. Chapter 20 Human Birth Defects
  1279. Classification of Birth Defects
  1280. Teratology: Study of Abnormal Development
  1281. FIGURE 20-1 Graphic illustration of the causes of human birth defects. Note that the causes of most defects are unknown and that 20% to 25% of them are caused by a combination of genetic and environmental factors (multifactorial inheritance).
  1282. Birth Defects Caused by Genetic Factors*
  1283. FIGURE 20-2 Diagram showing nondisjunction of chromosomes during the first meiotic division of a primary oocyte resulting in an abnormal oocyte with 24 chromosomes. Subsequent fertilization by a normal sperm produces a zygote with 47 chromosomes—aneuploidy—deviation from the human diploid number of 46.
  1284. Numerical Chromosomal Abnormalities
  1285. Glossary of Teratologic Terms
  1286. Inactivation of Genes
  1287. Aneuploidy and Polyploidy
  1288. FIGURE 20-3 Female infant with Turner syndrome (45, X0). A, Face of the infant with Turner syndrome. B, Lateral view of infant’s head and neck showing a short webbed neck, prominent ears. These infants have defective gonadal development (and gonadal dysgenesis). C, Infant’s feet showing the characteristic lymphedema (puffiness and swelling), a useful diagnostic sign. D, Lymphedema of toes, a condition that usually leads to nail underdevelopment (hypoplasia).
  1289. FIGURE 20-4 Turner syndrome in a 14-year-old girl. Note the features of the syndrome: short stature, webbed neck, absence of sexual maturation, broad shield-like chest with widely spaced nipples, and lymphedema of the hands and feet.
  1290. FIGURE 20-5 Female fetus (16 weeks) with Turner syndrome. Note the excessive accumulation of watery fluid (hydrops) and the large cystic hygroma (lymphangioma) in the posterior head and cervical region. The hygroma causes the loose neck skin and webbing seen postnatally (see Fig. 20-3B).
  1291. FIGURE 20-6 A, Anterior view of a female fetus (16.5 weeks) with Down syndrome. B, Hand of fetus. Note the single, transverse palmar flexion crease (simian crease, arrow) and the clinodactyly (incurving) of the fifth digit. C, Anterior view of the faces of dizygotic male twins that are discordant for Down syndrome (trisomy 21). The one on the right is smaller than the unaffected twin. The twin on the right developed from a zygote that contained an extra 21 chromosome. Note the characteristic facial features of Down syndrome in this infant: upslanting palpebral fissures, epicanthal folds, and flat nasal bridge. D, A 2–year-old girl with Down syndrome.
  1292. Turner Syndrome
  1293. Trisomy of Autosomes
  1294. Table 20-1 Trisomy of Autosomes
  1295. Trisomy of Sex Chromosomes
  1296. FIGURE 20-7 Female neonate with trisomy 18. Note the growth retardation, clenched fists with characteristic positioning of the fingers (second and fifth ones overlapping the third and fourth ones), short sternum, and narrow pelvis.
  1297. Table 20-2 Incidence of Down Syndrome in Neonates
  1298. FIGURE 20-8 Female neonate with trisomy 13. Note the bilateral cleft lip, low-set malformed left ear, and polydactyly (extra digits). A small omphalocele (herniation of viscera into umbilical cord) is also present.
  1299. FIGURE 20-9 Adolescent male with Klinefelter syndrome (XXY trisomy). Note the presence of breasts; approximately 40% of males with this syndrome have gynecomastia (development of breasts) and small testes.
  1300. Table 20-3 Trisomy of Chromosomes
  1301. Tetrasomy and Pentasomy
  1302. Mosaicism
  1303. Triploidy
  1304. Tetraploidy
  1305. FIGURE 20-10 Triploid fetus (69 chromosomes) illustrating severe head-to-body disproportion. Triploid fetuses account for nearly 20% of chromosomally abnormal miscarriages.
  1306. Structural Chromosomal Abnormalities
  1307. Translocation
  1308. Deletion
  1309. FIGURE 20-11 Diagrams illustrating various structural chromosomal abnormalities. A, Reciprocal translocation. B, Terminal deletion. C, Ring chromosome. D, Duplication. E, Paracentric inversion. F, Isochromosome. G, Robertsonian translocation. Arrows indicate how the structural abnormalities are produced.
  1310. FIGURE 20-12 A, Male child with cri du chat syndrome (cat-like cry). Note microcephaly (small neurocranium) and hypertelorism (increased distance between orbits). B, Partial karyotype of this child showing a terminal deletion of the short arm (end) of chromosome number 5. The arrow indicates the site of the deletion.
  1311. Microdeletions and Microduplication
  1312. Molecular Cytogenetics
  1313. Duplications
  1314. Table 20-4 Examples of Contiguous Gene Syndromes (Microdeletion or Microduplication Syndromes)
  1315. Inversion
  1316. Isochromosomes
  1317. Birth Defects Caused by Mutant Genes
  1318. FIGURE 20-13 A young boy with achondroplasia showing short stature, short limbs and fingers, normal length of trunk, bowed legs, a relatively large head, prominent forehead, and depressed nasal bridge.
  1319. FIGURE 20-14 Siblings with fragile X syndrome. A, An 8-year-old mentally deficient boy exhibiting a relatively normal appearance with a long face and prominent ears. B, His 6-year-old sister who also has this syndrome. She has a mild learning disability and similar features of long face and prominent ears. Note the strabismus (crossed right eye). Although an X-linked disorder, sometimes female carriers have expression of the disease.
  1320. Table 20-5 Examples of Disorders in Humans Associated with Homeobox Mutations
  1321. Developmental Signaling Pathways
  1322. Birth Defects Caused By Environmental Factors
  1323. Principles of Teratogenesis
  1324. Critical Periods of Human Development
  1325. Table 20-6 Some Teratogens Known to Cause Human Congenital Anomalies or Birth Defects
  1326. FIGURE 20-15 Schematic illustration of critical periods in human prenatal development. During the first 2 weeks of development, the embryo is usually not susceptible to teratogens; a teratogen either damages all or most of the cells, resulting in death of the embryo, or damages only a few cells, allowing the conceptus to recover and the embryo to develop without birth defects. Mauve denotes highly sensitive periods when major birth defects may be produced (e.g., amelia, absence of limbs, neural tube defects, spina bifida cystica). Green indicates stages that are less sensitive to teratogens when minor defects may be induced (e.g., hypoplastic thumbs).
  1327. FIGURE 20-16 Schematic illustration showing the increasing risk of birth defects developing during organogenesis.
  1328. Table 20-7 Incidence of Major Defects in Human Organs at Birth*
  1329. Dose of the Drug or Chemical
  1330. Genotype (Genetic Constitution) of the Embryo
  1331. Human Teratogens
  1332. Proof of Teratogenicity
  1333. Drug Testing in Animals
  1334. Drugs as Teratogens
  1335. Cigarette Smoking
  1336. Alcohol
  1337. FIGURE 20-17 Fetal alcohol syndrome in an infant. Note the thin upper lip, elongated and poorly formed philtrum (vertical groove in medial part of upper lip), short palpebral fissures, flat nasal bridge, and short nose.
  1338. Androgens and Progestogens
  1339. FIGURE 20-18 Masculinized external genitalia of a 46, XX female infant. Observe the enlarged clitoris and fused labia majora. The virilization was caused by excessive androgens produced by the suprarenal glands during the fetal period (congenital adrenal hyperplasia). The arrow indicates the opening of the urogenital sinus.
  1340. Antibiotics
  1341. Anticoagulants
  1342. Anticonvulsants
  1343. Antineoplastic Agents
  1344. FIGURE 20-19 Fetal hydantoin syndrome in a young girl. A, She has a learning disability due to microcephaly and mental deficiency. Note the large ears, wide space between the eyes (hypertelorism), epicanthal folds, and short nose. Her mother has epilepsy and ingested Dilantin throughout her pregnancy. B, Right hand of the girl with severe digital hypoplasia (short fingers) born to a mother who took Dilantin throughout her pregnancy.
  1345. Corticosteroids
  1346. Angiotensin-Converting Enzyme Inhibitors
  1347. Insulin and Hypoglycemic Drugs
  1348. Retinoic Acid (Vitamin A)
  1349. Analgesics
  1350. Thyroid Drugs
  1351. Tranquilizers
  1352. FIGURE 20-20 Neonate male infant showing typically malformed limbs (meromelia—limb reduction) caused by thalidomide ingested by his mother during the critical period of limb development.
  1353. Psychotropic Drugs
  1354. Illicit Drugs
  1355. Environmental Chemicals as Teratogens
  1356. Organic Mercury
  1357. Lead
  1358. Polychlorinated Biphenyls
  1359. Infectious Agents as Teratogens
  1360. Rubella (German Measles)
  1361. Cytomegalovirus
  1362. Herpes Simplex Virus
  1363. Varicella (Chickenpox)
  1364. Human Immunodeficiency Virus
  1365. Toxoplasmosis
  1366. Congenital Syphilis
  1367. FIGURE 20-21 Chorioretinitis of congenital ocular toxoplasmosis induced by Toxoplasma infection. A, Necrotizing cicatricial lesion of macula (arrow). B, Satellite lesion around and adjacent to necrotizing cicatricial main lesion (arrows). C, Recrudescent lesion adjacent to large necrotizing cicatricial main lesion (arrows).
  1368. FIGURE 20-22 Congenital cerebral defectsinduced by Toxoplasma infection. The diagnostic images were obtained at 2 years and 9 months of age. A, Plain CT (computed tomography) scan. The lateral ventricles are moderately dilated. Multiple calcified foci are apparent in the brain parenchyma (arrows 1), and along the ventricular wall (arrow 2). B, MRI (magnetic resonance imaging), T1 WI (400/22, 0.5 T). The cortical gyri are widened on the left side and the cortex is thickened in the left frontal lobe (arrow) compared with corresponding structure on the right. C, MRI, T2 WI (2,500/120, 0.5 T). The left frontal lobe shows abnormal hypointensity (arrow).
  1369. Radiation as a Teratogen
  1370. Ultrasonic Waves
  1371. Maternal Factors as Teratogens
  1372. Mechanical Factors as Teratogens
  1373. Birth Defects Caused By Multifactorial Inheritance
  1374. FIGURE 20-23 Multifactorial threshold model. Liability to a trait is distributed normally with a threshold dividing the population into unaffected and affected classes.
  1375. Summary of Human Birth Defects
  1376. Clinically Oriented Problems
  1377. Case 20–1
  1378. Case 20–2
  1379. Case 20–3
  1380. Case 20–4
  1381. Case 20–5
  1382. References and Suggested Reading
  1383. Chapter 21 Common Signaling Pathways Used During Development
  1384. Intercellular Communication
  1385. Gap Junctions
  1386. Table 21-1 International Nomenclature Standards for Genes and Proteins
  1387. FIGURE 21-1 Gap junction intercellular communication. A, The connexin molecule consists of four transmembrane domains, two extracellular domains and its N- and C-termini are cytoplasmic. B, Connexons, or hemi-channels, are hexameric structures consisting of 6 connexin subunits. A gap junction can be formed from two homophilic or heterophilic connexons. Small molecules (including ions and ATP) less than 1 kDa can pass through an open gap junction.
  1388. Cell Adhesion Molecules
  1389. Cadherins
  1390. Immunoglobulin Superfamily
  1391. FIGURE 21-2 Structure of cadherin and neural cell adhesion molecule (NCAM). A, The cadherin extracellular domain contains four calcium-binding sites and five repeated domains called extracellular cadherin domains (ECD). Each cadherin molecule forms a homodimer. On the intracellular domain, cadherin bind directly to p120 catenin and to β-catenin, which binds to α-catenin. This complex links the cadherin molecules to the actin cytoskeleton. B, Extracellularly, NCAM contains five immunoglobulin (Ig) repeats and two fibronectin-III domains. The fifth Ig repeat is modified by polysialyation, which decreases the adhesiveness of the NCAM molecule. Intracellular signaling is transmitted by the Fyn and Fak kinases.
  1392. Morphogens
  1393. Retinoic Acid
  1394. Transforming Growth Factor β/Bone Morphogenetic Protein
  1395. FIGURE 21-3 Regulation of retinoic acid metabolism and signaling. Dietary retinol (vitamin A) is converted to retinal via the action of retinol dehydrogenases. The concentration of free retinal is controlled by the action of cellular retinal–binding proteins. Similarly, retinal is converted to retinoic acid by retinal dehydrogenases, and its free level is modulated by sequestration by cellular retinoic acid–binding proteins and degradation by CYP26. The bioactive form of retinoic acid is all-trans retinoic acid.
  1396. FIGURE 21-4 Transforming growth factor β (TGF-β)/Smad signaling pathway. A, The type II TGF-β receptor subunit (TβR-II) is constitutively active. B, Upon binding of ligand to TβR-II, a type I receptor subunit is recruited to form a heterodimeric receptor complex and the TβR-I kinase domain is transphosphorylated (-P). Signaling from the activated receptor complex phosphorylates R-Smads, which then bind to a co-Smad, translocate from the cytoplasm to the nucleus, and activate gene transcription with cofactor(s) (X).
  1397. Hedgehog
  1398. Wnt/β-Catenin Pathway
  1399. FIGURE 21-5 Sonic hedgehog/Patched signaling pathway. A, The Patched (Ptc) receptor inhibits signaling from the Smoothened (Smo) receptor. In a complex with Costal-2 (Cos2) and Fused (Fu), Gli is modified to become a transcriptional repressor, Gli-R. B, Sonic hedgehog (Shh) is cleaved and cholesterol is added to its N-terminus. This modified Shh ligand inhibits the Ptc receptor, permitting Smo signaling, and ultimately activated Gli (Gli-A) translocates to the nucleus to activate target genes with CBP. In vertebrates, Shh signaling takes place in primary cilia (inset). CBP, cyclic AMP–binding protein; CKI, casein kinase I; GSK-3, glycogen synthase kinase-3; P, phosphate group; PKA, protein kinase A; SuFu, suppressor of Fused.
  1400. FIGURE 21-6 Wnt/β-catenin canonical signaling pathway. A, In the absence of Wnt ligand binding to Frizzled (Fzd) receptor, β-catenin is phosphorylated (-P) by a multiprotein complex and targeted for degradation. Target gene expression is repressed by T-cell factor (TCF). B, When Wnt binds to the Fzd receptor, LRP coreceptors are recruited, Dishevelled (DVL) is phosphorylated, and β-catenin then accumulates in the cytoplasm. Some β-catenin enters the nucleus to activate target gene transcription. APC, adenomatous polyposis coli; GSK-3, glycogen synthase kinase-3; LRP, lipoprotein receptor–related-protein.
  1401. Receptor Tyrosine Kinases
  1402. Common Features
  1403. FIGURE 21-7 Receptor tyrosine kinase (RTK) signaling. A, In the absence of ligand, the receptors are monomers and are inactive. B, Upon binding of ligand, the receptors dimerize and transphosphorylation occurs, which activates downstream signaling cascades. P, phosphorylated.
  1404. Regulation of Angiogenesis by Receptor Tyrosine Kinases
  1405. FIGURE 21-8 Notch/Delta signaling pathway. In progenitor cells (right), activation of Notch signaling leads to cleavage of the Notch intracellular domain (NICD). Proteases such as γ-secretase mediate this cleavage event. NICD translocates to the nucleus, binds to a transcriptional complex, and activates target genes, such as Hes1, that inhibit differentiation. In differentiating cells (left), Notch signaling is not active.
  1406. Notch-Delta Pathway
  1407. Transcription Factors
  1408. Hox/Homeobox Proteins
  1409. Pax Genes
  1410. Basic Helix-Loop-Helix Transcription Factors
  1411. Epigenetics
  1412. Histone Acetylation
  1413. DNA Methylation
  1414. FIGURE 21-9 Epigenetic modifications alter transcriptional properties of chromatin. A, In areas of transcriptionally inactive chromatin, the DNA is tightly bound to the histone cores. The histones are not acetylated or phosphorylated. Histone deacetylases (HDACs) are active, whereas histone acetyl transferases (HATs) and histone kinases are inactive. DNA is highly methylated (Me). B, In areas of transcriptionally active chromatin, the DNA is not as tightly bound to the histone cores and the DNA in unmethylated. The histone proteins are acetylated (Ac) and phosphorylated (-P). HDACs are inactive, whereas HATs and histone kinases are active.
  1415. Stem Cells: Differentiation Versus Pluripotency
  1416. FIGURE 21-10 Neural stem cells and induced pluripotent stem cells. A, Adult or embryonic stem cells can either divide symmetrically, giving rise to two equivalent daughter stem cells, (“vertical” cell division; the plane of mitosis is perpendicular to the ventricular surface) or asymmetrically, giving rise to a daughter stem cell and a nervous system progenitor cell (“horizontal” cell division: the plane of mitosis is parallel to the ventricular surface). In this example, the progenitor cell does not retain the nuclear or cytoplasmic factors (colored shapes) that remain in the stem cell; however, the progenitor cell expresses new proteins (e.g. receptor tyrosine kinases) in its plasma membrane. B, Stem cells and induced pluripotent stem cells (iPS) have the capacity for self-renewal, cell death and/or to become progenitors. Progenitor cells have a more limited capacity for self-renewal, but also can differentiate into various cell types or undergo cell death. Adult, differentiated somatic cells, such as skin fibroblasts, can be reprogrammed into iPS with the introduction of the master transcription factors SOX2, Oct-3/4, or KLF4.
  1417. Summary of Common Signaling Pathways Used During Development
  1418. References and Suggested Reading
  1419. Appendix Discussion of Clinically Oriented Problems
  1420. Chapter 1
  1421. Chapter 2
  1422. Chapter 3
  1423. Chapter 4
  1424. Chapter 5
  1425. Chapter 6
  1426. Chapter 7
  1427. Chapter 8
  1428. Chapter 9
  1429. Chapter 10
  1430. Chapter 11
  1431. Chapter 12
  1432. Chapter 13
  1433. Chapter 14
  1434. Chapter 15
  1435. Chapter 16
  1436. Chapter 17
  1437. Chapter 18
  1438. Chapter 19
  1439. Chapter 20
  1440. Index

 

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