Embryo

Question 1

Cardiac looping

Answer 1

heart beats at week 4

primary heart tube establishes L-R polarity through dynein movement (Kartagener’s = dextrocardia)

Question 2

Atria formation

Answer 2

Septum primum forms, then detaches at each end to stay in the middle (top hole = foramen secundum, bottom = foramen primum)
Septum secundum first covers most of foramen secundum, then all of foramen primum
Remaining hole of foramen secundum is the foramen ovale (septum primum serves as valve)

Question 3

Ventricle formation

Answer 3

interventricular foramen is closed by the fusion of muscular septum and aorticopulmonary septum (comes from neural crest!)

Question 4

Outflow tract

Answer 4

neural crest cells and endocardial cell migrations allow for travel and bulbar ridges that form aorticopulmonary septum

Question 5

Valve development

Answer 5

• aortic/pulmonary valves: endocardial cushion of outflow tract
• mitral/tricuspid: endocardial cushion of AV canals

Question 6

Fetal erythropoiesis locations

Answer 6

3-8 wks: yolk sac
6 wks - birth: liver***
10-28 weeks: spleen
18 weeks - birth: bone marrow

Question 7

Fetal circulations (give 3 shunts)

Answer 7

Ductus venosus: umbilical vein to IVC (bypass portal system)
Foramen ovale: RA to LA (bypass cardiopulmonary system)
Ductus arteriosus: Left PA to descending aorta (bypass lungs)

Question 8

How can the closure of the DA be manipulated? (accel closure, prevent closure)

Answer 8

Accel closure: indomethacin, NSAIDs (block PGs)

Prevent closure: prostaglandins E1, E2

Question 9

Notable vessels to ligaments

Answer 9

Allantois - urachus: median umbilical ligament
Notochord: nucleus pulposus
Umbilical arteries: medial umbilical ligaments
Umbilical vein: ligamentum teres hepatis (falciform ligament)

Question 10

Thyroid diverticulum

Answer 10

primitive pharynx –> descends to neck
(connected to tongue by thyroglossal duct - if duct persists, become pyramidal lobe of thyroid)
most common site of ectopic thyroid tissue: tongue

Question 11

Thyroglossal duct cyst

Answer 11

Anterior midline neck mass, moves with swallowing

Question 12

Anterior abdominal wall defects

Answer 12

rostral (head) folds: sternal defects
lateral folds: omphalocele (sealed by peritoneum), gastroschisis
caudal (butt) folds: bladder exstrophy

Question 13

Duodenal atresia is seen with what genetic condition?

Answer 13

Trisomy 21! Arises due to failure of recanalization. Look for double bubble sign and bilious vomiting (or polyhydramnios)

Question 14

A vascular accident early in development causes what abdominal abnormality?

Answer 14

Jejunal/ileal/colonic atresia
Can be complete obliteration of intestine
Look for polyhydramnios

Question 15

Midgut development (ampulla of Vader to proximal 2/3 of transverse colon)

Answer 15

6th week: herniates through umbilical ring

10th week: returns to abdominal cavity, rotates around SMA

Question 16

Pancreas development

Answer 16

Ventral bud = uncinate process and main duct
encircles duodenum in annular pancreas, can cause obstructive symptoms
Dorsal bud: body, tail, isthmus, accessory duct

Pancreatic divisum: failure of fusion of buds (which normally occurs at 8 weeks), can be a cause of pancreatitis

Question 17

Notochord function and development

Answer 17

induces overlying ectoderm to become neuroectoderm –> neural plate –> neural tube and neural crest cells

Question 18

Regional specification of developing brain (3 regions become 5 regions)

Answer 18

Forebrain:
telencephalon: hemispheres/lateral ventricle
diencephalon: thalamus/third ventricle
Midbrain:
mesencephalon: midbrain/aqueduct
Hindbrain:
metencephalon: pons/cerebellum/4th ventricle
myelencephalon: medulla/lower 4th ventricle

Question 19

CNS/PNS progenitors

Answer 19

neuroectoderm –> CNS, glial cells (ependymal, oligodendroglial, astrocytes)
neural crest –> PNS neurons, Schwann cells
mesoderm –> microglia (come from macrophages!)

Question 20

Neural tube defects

Answer 20

Failure of cranial neuropore to close: anencephaly
Failure of caudal neuropore to close: spina bifidas
Spina bifida occulta: bones don’t close, no herniation, intact dura (normal AFP)
Meningocele: meninges herniates (can be caused by teratoma)
Myelomeningocele: meninges and neural tissue herniate

Question 21

Posterior fossa malformations

Answer 21

Chiari Arnold II: herniation of cerebellar tonsils through the foramen magnum, often seen myelomeningocele

Dandy-Walker: agenesis of vermis with cystic enlargement of 4th ventricle, seen with hydrocephalus and spina bifida

Question 22

Synringomyelia

Answer 22

cystic cavity within spinal cord, leads to damage of anterior commisures and subsequent cape-like distribution of pain/temp loss
Most often occurs at C8-T1

Question 23

Tongue development

Answer 23

1st/2nd arches: anterior 2/3 (CN V3, CN VII)
3rd/4th arches: posterior 1/3 (CN IX, CN X)

Motor: CN XII (except CN X to palatoglossus)

Question 24

Renal development

Answer 24

Pronephros: week 4, then degenerates (turns into nothing!)
Mesonephros: interim kidney for 1st trimester (then, contributes to male genitals)
Metanephros: appears in Wk 5, forms permanent kidney
- ureteric bud: caudal (butt) end of metanephros, becomes ureter, pelvises, calyces, CDs
- metanephric mesenchyme: glomerulus through DCT

Ureteropelvic junction = last to canalize, most common site of obstruction (hydronephrosis)

Question 25

Oligohydramnios/Potter sequence

Answer 25

ADPKD, obstructive uropathy causes decreased amniotic fluid

Compression of fetus –> limb deform, facial anomalies –> compression of chest/lack of fluid in lungs –> pulmonary hypoplasia

Question 26

Kidney abnormalities:
Horseshoe kidney
Multicystic dysplastic kidney
Duplex collecting system

Answer 26

inferior poles fuse –> trapped under IMA –> kidneys remain low in abdomen (increased risk of obstruction, hydronephrosis, renal stones, infection, etc.)

abnormal interaction between ureteric bud and metanephric mesenchyme –> nonfunctional kidney of cysts and connective tissue

Bifurcation of ureteric bud creates Y-shaped bifid ureter. Assoc w/ vesciureteral reflux and/or ureteral obstruction (increased risk of UTIs)

Question 27

Genes involved in early development (Shh, Wnt-7, FGF, Hox)

Answer 27

Shh - anterior-posterior patterning, ZPA
Wnt-7 - dorsal-ventral patterning, apical ectodermal ridge
FGF - stimulates mitosis of mesoderm, limb lengthening
Hox - segmental organization, transcription factors

Question 28

Early development (give events by week)

Answer 28

Wk 1: implantation of blastocyst, secretion of bHCG
Wk 2: bilaminar disc
Wk 3: trimlaminar disc (three germ layers)
Wk 4: neural tube closure, heart beats
Wk 4-8: organogenesis, susceptible to teratogens!
Wk 6: heart visible
Wk 10: sex-distinguishable genitalia

Question 29

Ectoderm derivatives (surface ectoderm, neuroectoderm, neural crest)

Answer 29

Surface ectoderm: epidermis, oral cavity, ears, nose, glands (parotid, sweat, mammary), *cranipharyngioma

Neuroectoderm: Brain, spinal cord, optic nerve, posterior pituitary

Neural crest: PNS, melanocytes, adrenal medulla (chromaffin), skull, **aorticopulmonary system

Question 30

Mesoderm derivatives

Answer 30

Muscle, bone, connective tissue, CV structures, lymph, blood,

VACTERL: Vertebral defects, Anal atresia, Cardiac defects, Tracheo-Esophageal fistula, Renal defects, Limb defects

Question 31

Endoderm derivatives

Answer 31

Gut tube epithelium, urethra (from urogenital sinus), lungs, liver, GB, pancreas, eustachian tube, parathyroid

Question 32

Notable teratogens, give their effects

Aminoglycosides
Lithium
Phenytoin
Tetracyclines
Warfarin

Answer 32

Aminoglycosides - Cn VIII toxicity
Lithium - Ebstein anomaly (atrialized R ventricle, disp of tricuspid)
Phenytoin - fetal hydantoin (cleft palate, cardiac defects, fingernail hypoplasia)
Tetracyclines - discolored teeth
Warfarin - bone deformities, fetal hemorrhage, abortion

Question 33

Twinning

Answer 33

0-4 days: Di/di
4-8 days: Mono/di
8-12 days: Mono/mono
>13 days: conjoined

Dizygotic (80%) - 2 eggs fertilized separately, di/di

Question 34

Placental cells

Answer 34

Fetal: syncytiotrophoblasts - decreased MHC-1 reduces chance of attack by maternal immune system
Maternal: decidua basalis - endometrium derivative, maternal blood flows in lacunae

Question 35

Umbilical cord anatomy

Answer 35

1 vein (blood from mom to fetus)
2 arteries (1 from each internal iliac of fetus to mom)
Surrounded by Wharton jelly
Derived from allantois

Question 36

Urachus

Answer 36

Yolk sac becomes allantois becomes urachus (duct from fetal bladder to yolk sac)

Patent urachus = failure to obliterate, urine discharge from umbilicus
Urachal cyst = partial failure to obliterate, fluid-filled cavity lined with uroepithelium (infection, adenocarcinoma)
Vesicourachal diverticulum = slight failure of urachus to obliterate, leads to outpouching of bladder

Question 37

Vitelline duct

Answer 37

Goes from midgut lumen to yolk sac

Vitelline fistula = meconium discharge from umbilius
Meckel diverticulum = partial closure, leads to patent portion with gastric/pancreatic tissue

Question 38

Aortic arches (develop into arterial system)

Answer 38

1st = maxillary artery
2nd = stapedial artery, hyoid artery
3rd = common carotid, proximal internal carotid
4th = aortic arch (left), R subclavian (right)
6th = pulmonary arteries, ductus arteriosus (left)

Question 39

Branchial clefts (ectoderm!)

Answer 39

1st: EAM
2nd-4th = temporary cervical sinuses

persistent cervical sinus become branchial cleft cyst!

Question 40

Branchial arches

Answer 40

1st (mandibular) = muscles of mastication, CN V2/V3 (Treacher Collins = mandibular hypoplasia)
2nd (pharyngeal) = stapes, styloid, CN VII
3rd = stylopharyngeus, CN IX
4th-6th = cartilages of neck (thyroid, cricoid, etc.), CN X, CN X

Question 41

Branchial pouches (endoderm!)

Answer 41

1st = middle ear, eustachian tube 
2nd = tonsils
3rd = inferior parathyroid, thymus (end up below 4th pouch structures)
4th = superior parathyroid

DiGeorge: abnormal 3rd and 4th

MEN 2A: germline RET mutation (neural crest cells) –> medullary thyroid, pheochromocytoma (adrenal medulla) 4th pouch, parathyroid 3rd/4th pouches

Question 42

Genital embryology

Answer 42

Female: mesonephric duct degenerates, paramesonephric (Mullerian ) –> internal structures
Male: SRY = MIF, leads to suppression of paramesonephrics, Leydig (testosterone) stimulates mesonephric (Wolffian) to internal structures

Low MIF/No Sertoli = both male/female internal, only male external
5a-reductase def (no DHT) = male internal, ambiguous external

Question 43

Male/female homologs (male = DHT, female = estrogen)

Answer 43

tubercle –> glans (penis, clitoris)
urogenital sinus –> Cowper/prostate or Bartholin/Skene glands
urogenital folds –> ventral shaft or labia minora
labioscrotal swelling –> scrotum or labia majora

Question 44

Spadias

Answer 44

Hypo = ventral opening, failure of urethral folds to fuse
Epi = faulty positioning of genital tubercle (exstrophy of bladder)

Question 45

Descent of ovaries and testes

Answer 45

Gubernaculum (band of fibrous tissue) = anchors testes in scrotum, also forms ovarian ligament + round ligament
Processus vaginalis = forms tunica vaginalis, obliterated in females