the anatomic basis of fetal medicineEmbryology • Fundamental understanding of key events ... •...
Transcript of the anatomic basis of fetal medicineEmbryology • Fundamental understanding of key events ... •...
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Embryology the anatomic basis of fetal medicine
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Prenatal consult
• You meet with expectant parents and tell them that a congenital malformation has been identified.
• You proceed to explain the birth defect.
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Predictable questions
• Why did that happen? • Is it something we passed on to the baby? • Did we expose the baby to something that
caused this? • What else can be wrong? • What does it take to fix everything • Can we do something to prevent problems
before the baby is born?
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Embryology
• Fundamental understanding of key events in development of the fetus
• Basis for rational prenatal evaluation • Basis for postnatal evaluation and
Treatment
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“Early Cellular” events
• Fertilization, cleavage….Blastomere to morula
• “Physical events” – Twin gestations, incomplete separation,
• “Information events” –heritable/sporadic – Genetic disorders
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Monozygotic Twins Aberrancies in cleavage process
Completely separated after 2-cell stage – two chorionic cavities, two amniotic cavities. Separate uterine implantations
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Monozygotic Twins Aberrancies in cleavage process
Separation of inner cell mass at later stages of development- resulting in common placenta – One chorionic cavity mono-chorionic A) separate amniotic
cavities B) Single amniotic
cavity A B
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Dichorionic, diamniotic membranes
Monochorionic diamniotic membranes
Monochorionic Monoamniotic membranes
Which twins are at risk for Twin-twin Transfusion syndrome?
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Wolf Hirschhorn Syndrome
• Transmission of faulty genetic “directions” • Example: microdeletion on short arm of chromosome 4 • Aneuploidy disorders – some fatal • Mitochondrial disorders -
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Terminology • Week 1 - ovulation to implantation
– Blastomeres / morula/ blastocyst – Trophoblast / embryoblast
• Week 2 - bilaminar germ disk – Endometrial embedding- development of placenta – Establishment of uteroplacental circulation by day 13 – Embryoblast – forms bilaminar germ disk and amniotic
cavity lining develops • Week 3 - trilaminar germ disk
– Gastrulation – formation of 3 germ cell layers – Establishment of body axes
• Week 4-8 embryonic period • 3rd month to birth = fetal period
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This is only 27 units/cells!!!
Events have to occur in correct spatial and correct time sequence
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the Morula enters uterine cavity- and forms the blastocyst by day 9 1) Trophoblast (green) 2) Embryoblast ( blue/yellow)
Trimester 2 Trimester 1 Trimester 3
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Day 12 – further embedding into endometrium
Trimester 2 Trimester 1 Trimester 3
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Day 13: Established uteroplacental circulation Bilaminar disk stage
Week 2
Future umbilical cord
Trimester 2 Trimester 1 Trimester 3
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Gastrulation: Development of tri-laminar disk
Derivation of the three germ cell layers
Week 3
Epiblast cells invaginate to form mesoderm
Trimester 2 Trimester 1 Trimester 3
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Gastrulation: Development of tri-laminar disk
Derivation of the three germ cell layers
Establishment of body axes Looking onto ectoderm from above
Week 3
Fate map for epiblast cells pm: paraxial mesoderm= somites Im: intermed mesoderm= urogenital system, Lpm:lateral plate mesoderm= lateral body wall, eem:extraembryonic meso= chorion
Trimester 2 Trimester 1 Trimester 3
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Teratogenesis
– Holoprosencephaly: – injury to anterior midline of germ disk-
alcohol exposure / via SHH gene – Fusion of the eyes. – Single nasal chamber
Examples of failures at gastrulation
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Teratogenesis • Examples of failures at gastrulation
– Caudal dysgenesis – • Injury to caudal end of disk
Example: 22-week fetus. The lower portion of the body is small compared with the midbody and chest. The lower extremities (arrows) appear abnormally extended and atrophied. Structures above the level of L3 and intracranial anatomy appear normal.
Source:radiology.rsnajnls.org/cgi/content/full/230/1/229
Day 28 of gestation Affects mesodermal derivatives ?lack of vascular supply? May be related to mat’l diabetes
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Teratogenesis • Examples of failures at
gastrulation – Situs inversus – – Generally autosomal recessive
disorder – 5-10% have CHD most often
transposition of the great vessels – If situs with levocardia (1in 2Mill)
then 95% risk CHD – 25% will have primary ciliary
dyskinesia (PCD) – 50% of PCD have Situs
inversus= Kartagener syndrome siuts, sinusitis, bronchiectasis male infertility
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Teratogenesis • Examples of failures at
gastrulation – Sacrococcygeal tumors – arise from
remnants of primitive streak.
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Midline cervical mass
Dermoid cyst or thyroglossal duct cyst?
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Principle of “cyst” excision is complete excision
• Dermoid cyst – simple excision of the mass
• Thyroglossal duct cyst – • Must understand embryology
of thyroid descent
• Requires excision of mid-portion of hyoid bone to avoid recurrence
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The embryonic period • Ectoderm, mesoderm and endoderm give rise to
specific tissues and organs
Trimester 2 Trimester 3 Wk 4-8
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Germ Cell Derivatives
• Ectoderm – – neural system, skin and appendages that relate to
external environment (eyes, ears…) • Mesoderm –
– musculoskeletal tissues, genitourinary system, body wall and membranes lining the cavities
• Endoderm – – foregut, midgut and hindgut – GI tract and
appendages (liver, pancreas) respiratory tract, bladder
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The embryonic period
• Complex set of folding patterns, cell migrations give rise to embryo structure/form
Transverse axis view
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View along longitudinal axis (head – tail)
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Specific embryology
• Development of – 1) the body cavities- thoracic/abdominal – 2) the respiratory system – 3) the GI tract – 4) the urogenital system
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Ventral Body Wall Defects • Failure of in-folding or incomplete development of
component tissues
Consequences of failure:……
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Gastroschisis
Herniation of bowel through defect in abdominal wall – always to the right of umbilicus- Exposed intestine
Omphalocele
Herniation through umbilical ring intestine covered by membrane
Question: Is it ever normal to see intestine outside the confines of the abdominal wall?
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Pleuro-peritoneal separation and development of the diaphragm
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Congenital diaphragmatic hernia aka Posterolateral / Bochdalek hernia
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Morgagni Hernia – anterior defect in diaphragm
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Development of Respiratory System
25 days 5 week embryo
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Tracheo-esophageal separation
hea
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Failure of tracheo-esophageal separation
Which one(s) might you be able to dx prenatally?
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Broncho-alveolar development
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Pulmonary agenesis- If bronchioles don’t grow- Lung parenchyma doesn’t grow
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Pulmonary agenesis- If bronchioles don’t grow- Lung parenchyma doesn’t grow
Cystic adenomatoid malformation Proliferation of bronchioles, not alveoli- abnormal sac of lung tissue
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Pulmonary agenesis- If bronchioles don’t grow- Lung parenchyma doesn’t grow
Cystic adenomatoid malformation Proliferation of bronchioles, not alveoli
Pulmonary sequestration Separate piece of lung – not connected to Tracheobronchial tree Aortic blood supply
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Pulmonary agenesis- If bronchioles don’t grow- Lung parenchyma doesn’t grow
Cystic adenomatoid malformation Proliferation of bronchioles, not alveoli
Congenital lobar emphysema Absent musculature on bronchus Results in hyperinflation
Pulmonary sequestration Separate piece of lung – not connected to Tracheobronchial tree Aortic blood supply
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Other lesions
Bronchogenic Cyst Diverticulum of tracheobronchial tree w/o associated pulmonary parenchyma
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Other lesions
Bronchogenic Cyst Diverticulum of tracheobronchial tree w/o associated pulmonary parenchyma
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Gastrointestinal tract 1. Defects in the continuity of the intestine
Some are consequences of failures of normal developmental processes
Some are accidents of nature when development has been fine
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Gastrointestinal tract 1. Defects in the continuity of the intestine
Some are consequences of failures of normal developmental processes
Some are accidents of nature when development has been fine
Does this make a difference in what you expect the incidence of associated anomalies to be????
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Gastrointestinal tract
Duodenal atresia/ stenosis:
trisomy 21. cardiac defects, multiple
atresias
Jejunoileal atresia: No association with Genetic disorders or
Other organ involvement
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Gastrointestinal tract 2. Defects in the rotation of the intestine
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Impact for fetal medicine
• Embryology: – Provides understanding of a given anomaly – Prompts us to consider organ defects in organs
forming at same time – Allows us to search for genetic basis of disorders – Allows us to prepare parents for what the may need
to expect postnatally even if not evident prenatally
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References
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Di-chorionic, Di-amniotic membranes
Mono-chorionic di-amniotic membranes
Mono-chorionic Mono-amniotic membranes
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Dizygotic twins
2 oocytes Simultaneously fertilized – usually separate membranes, although they can fuse
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Teratogenesis • Examples of failures at gastrulation
– Conjoined twins – partial splitting of primitive node
http://library.med.utah.edu/WebPath/PEDHTML/PED022.html
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Urogenital System • Renal
– parenchymal development, retroperitoneal vs pelvic location, midline fusion
• Ureteral – Duplication anomalies, Insertion in bladder
• Bladder – Size/innervation/musculature – Development of bladder neck, continence
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