Embryology

Question 1

Sonic hedgehog gene

Answer 1

Produced: base of limbs (zone of polarizing activity)

Roles:

• A-P axis patterning
• CNS development

Mutation: holoprosencephaly

Question 2

Wnt-7 gene

Answer 2

Produced: apical ectodermal ridge (at end of each developing limb)

Role: Organize along dorsal-ventral axis

Question 3

FGF gene

Answer 3

Produced: apical ectodermal ridge

Role: mitosis of underlying mesoderm–> limb lengthening

Question 4

Homeobox (hox) genes

Answer 4

Transcription regulators (code DNA-binding transcription factors)

Segmental organization of embryo cranial–> caudal

Mutations: appendages in wrong locations

Question 5

Week 0-10 in development

Answer 5

Day 2= zygote
Day 3= morula
Day 5= blastocyst
Day 6= implantation in endometrium

Week 1= hCG secretion
Week 2= 2 layers (bilaminar disc= epi-, hypoblast)
Week 3= 3 layers (trilaminar disc)
- Epiblast invaginates–> primitive streak
- gastrulation= ecto-, meso-, endodermal layers
Week 4= neural tube closure, heartbeat
- 4 weeks= 4 limbs (limb bud formation)
Week 8= Fetal movement
Week 10= external F/M genitalia

**Weeks 3-8 (embryonic period)= organogenesis, v. susceptible to teratogens (malformations= intrinsic disruptions during embryonic period)

Question 6

Ectodermal derivatives

Answer 6

Surface ectoderm:

• Epithelium and epidermis
• Anterior pituitary
• Sensory organs of ear
• Lens of eye
• Parotid, sweat, mamillary glands

Neuroectoderm:
- Brain (post. pit), retina, optic nerve, spinal cord

Neural crest cells:

• PNS
• Bones of skull
• Odontoblasts
• Aorticopulmonary septum
• Melanocytes (melanoma= neural-crest derived tumor)

Question 7

Mesodermal derivatives

Answer 7

• Muscle, bone, cartilage, connective tissue
• Serous linings
• Spleen
• • Defects= VACTERL:
• Vertebral defects
• Anal atresia
• Cardiac defects
• Tracheo-Esophageal fistula
• Renal defects
• Limb defects

** Notochord (mesodermal) induces ectoderm–> neuroectoderm (neural plate)–> nucleus pulposus of IV disc

Question 8

Endoderm

Answer 8

Epithelium of internal structures
Luminal epithelium derivatives:
- Lungs
- Liver, gallbladder, pancreas
- Eustachian tube, thymus, Parathyroid, thyroid follicle cells (C cells= mesoderm)

Question 9

Agenesis

Answer 9

Absent organ d/t absent primordial tissue

Question 10

Aplasia

Answer 10

Absent organ despite present primordial tissue

Question 11

Maternal diabetes

Answer 11

• Caudal regression syndrome (anal atresia–> sirenomelia): baby with denervated/weak lower limbs
• Congenital heart defects
• Neural tube defects

Question 12

Twinning

Answer 12

Dizygotic twins (80%):

• 2 eggs, 2 sperm
• 2 aminiotic sacs, 2 chorions (placentas)

Monozygotic twins (20%):

• Divide at 2 cell stage (0-4 days): 2 + 2
• Divide at Morula (4-8 days): monochorionic, diaminiotic *most common
• Divide at blastocyst (8-12 days): monochorionic, monoamniotic
• Divide after embryonic disc formed (13 days)–> conjoined twins

Question 13

Placental development

Answer 13

Fetal component:

1. Cytotrophoblast: inner layer (cells)
2. Synciotrophoblast: outer layer (hCG)

Maternal component:
- Decidua basalis= derived from endometrium; maternal blood in lacunae

Question 14

Umbilical cord

Answer 14

Allantoid–> umbilical arteries/vein

2 Umbilical arteries: return DEoxygenated blood FROM feturs (internal iliacs) to placenta

1 umbilical vein: supplies oxygenated blood from placenta to fetus
- Drains: ductus venosus–> IVC

Question 15

Urachal duct

Answer 15

3rd week: yolk sac allantois–> urogenital sinus–> urachus (duct btwn bladder and yolk sac)

• Patent urachus= urine discharge from umbilicus
• Vesicourachal diverticulum= outpouching of bladder (asymptomatic)

Question 16

Vitelline duct

Answer 16

7th week: vitelline duct connects midgut lumen to yolk sac—> obliterates

• Vitelline fistula= meconium discharge from umbilicus
• Meckel’s diverticulum= partial closure with patent portion in ileum
• Ectopic gastric mucosa–> melena, periumbilical pain, ulcerations

Question 17

Aortic arch derivatives

Answer 17

1st arch= MAXimal (maxillary= branch of external carotid)

2nd arch= Stapedial (stapedial, hyoid aa)

3rd arch= Common Carotid, proximal internal Carotid (C= 3rd letter in alphabet)

4th arch= 4 limbs (systemic circulation)
- Aortic arch (L), Proximal subclavian (R)

6th arch= pulmonary artery, ductus arteriosus (pulmonary shunt)

Question 18

Branchial Clefts

Answer 18

ECTODERM

1st= external auditory meatus
2nd-4th= temporary cervical sinuses
- Obliteration by 2nd arch
** persistance cervial sinus–> branchial cleft cyst in lateral neck

Question 19

Branchial arches

Answer 19

MESODERM= cartilage tissue

1st= Chewing
(muscles of mastication, CN V2 and V3)
- Treacher collins= 1st arch neural crest fails to migrate–> mandibular hypoplasia, facial abnormalities

2nd= Smile
(muscles of facial expression, stapes/styloid/styloihyoid, CN VII)

3rd= Swallow stylishly
(Stylopharyngeus, CN IX)

4th= Simply swallow
(pharyngeal constrictors, cricothyroid, levator veli palatini, CN X= superior laryngeal branch)

6th= Speak
(all intrinsic muscles of larynx but cricothyroid), CNX (recurrent laryngeal branch)

“When at the golden arches, children tend to first Chew (1), then smile (2), then swallow stylishly (3), or simply swallow (4) and then speak (6)

Question 20

Branchial pouch derivatives

Answer 20

Ear, tonsils, bottom-to-top:
1= ear
2= tonsils
3= inferior (bottom) parathyroids
3= thymus (t= thymus)
4= superior parathyroids (top)

** 3rd pouch ends up below (bottom) 4th pouch (top)

• DiGeorge= abberrant development of 3rd and 4th pouches
• MEN2A= germline mutation of neural crest cells:
• Adrenal medulla (pheo)
• Parathyroid tumor (3rd/4th pharyngeal pouch)
• Parafollicular cells (medullary thyroid cancer)= 4th/5th pouches

Question 21

Genital embryology

Answer 21

Female= default

1. Mesonephros degenerates
2. Paramesonephros develops:
   - Female internal structures (besides ovaries)
   - Mullerian duct abnormal- Ovaries present (secondary sex characteristics) with defects in external genitalia

Male= SRY on Y-chrom
1. Produces Testis-determining factor (testes develop)

2. Testes–> sertoli cells–> Mullerian inhibiting factor (MIF)–> suppress development of paramesonephric ducts
   - No sertoli cells= no MIF–> have male and female internal genitalia, male external
3. Testes–> Leydig cells–> mesonephric duct development–> SEED
   * * SEED= seminal vesicles, epididymis, ejaculatory duct, ductus deferens (internal structures except prostate)
   - No 5-alpha reducase: Testosterone not converted to DHT–> have internal genitalia, NO external genitalia (induced by DHT) or prostate

Question 22

Leydig cells

Answer 22

Hypothalamus–> GnRH

• -> anteriorpituitary–> LH
• -> Leydig cells–> Testosterone
• -> blood–> inhibits GnRH and LH secretion
• Leydig cell function increases when 1 testis missing–> normal Testosterone (vs Sertoli cell mass= decreased–> less inhibin and ABP, more FSH

Question 23

Testosterone conversion

Answer 23

1. 5-alpha-reductase–> DHT
2. aromatase in adipose tissue and leydig–> estrogen
   - Also converts androstenedione (Adrenal gland)

DHT==> external genitalia, prostate growth, balding (5-alpha-reductase blocked by finasteride= med for balding, BPH)

Estrogen–> closure of epiphyseal plates

Question 24

Estrogen sources

Answer 24

1. 17-beta estradiol= ovary
   - 50-fold increase in pregnancy
2. Estriol= placenta
   - 1000-fold increase in pregnancy: derived from placenta- indicates fetal well-being
3. Estrone= adipose (aromatization)
   - 50-fold increase in pregnancy

Question 25

Progesterone

Answer 25

Source: - Corpus luteum (maintains placenta in 1st trimester; stimulated from BhCG) - Placenta (2nd, 3rd trimester - Adrenal cortex - Testes * * decreases myometrial and smooth muscle excitability (decreases contractions) * * maintains endometrium--> implantation * * Ovulation indicated by progesterone--> rise in body temp, thicker cervical mucous production Decreases estrogen receptor expression

Question 26

Pituitary stimulation of Progesterone, Estrogen formation

Answer 26

LH: increases Desmolase in Theca Interna - Cholesterol converted to progesterones, androstenedione FSH: increases Aromatase in Granulosa cells - Androstenedione--> estrogen * * Increased estrogen, GnRH receptors on anterior pituitary - -> LH surge - -> ovulation (secondary oocyte in metaphase II) - -> progesterone (corpus luteum) * No fertilization--> progesterone levels fall--> menstruation

Question 27

beta-hCG

Answer 27

Source: Syncytiotrophoblast of placenta Role: - Maintains corpus luteum for 1st trimester (acts like LH; no luteal stimulation--> abortion) * Detected in blood 1 week after conception * Detected in urine 2 weeks after 2nd/3rd trimester= placenta creates estriol/progesterone - Corpus luteum degenerates

Question 28

hPL

Answer 28

Human placental lactogen Source: Syncytiotrophoblast Role: - Similar to prolactin, GH - Increases maternal insulin resistance - Decreases maternal glucose utilization - Increases blood glucose--> shunted to fetus - Increases lipolysis, proteolysis= energy for mom so baby can use glucose Maternal insulin resistance due to: - hPL, GH, estrogens, progesterones, glucocorticoids - Gestational diabetes= unable to overcome insulin resistance

Question 29

Klinefelter's syndrome

Answer 29

XXY Hypogonadism: - Dysgenesis of seminiferous tubules--> decreased inhibin, increased FSH - Abnormal leydig cell function--> decreased testosterone--> increased LH--> increased estrogen Symtoms: - testicular atrophy - Eunuchoid body shape, tall, long extremities (Marfanoid habitus) - Gynecomastia, female hair distribution - Possible developental delay (determined by number of Xs)

Question 30

Cryptorchidism

Answer 30

Damage to seminiferous tubules (heat inside body) - Decreased inhibin--> increased FSH Leydig cells preserved - Normal testosterone, LH levels

Question 31

Pseudohermaphroditism

Answer 31

Female= XX - Ovaries present - External genitalia virilized, ambigious - Causes: congenital adrenal hyperplasia--> increased androgen exposure; maternal androgen administration Male= XY - Testes present - External genitalia female, ambiguous - Cause: androgen insensitvity (testicular feminization) True hermaphroditism= very rare (46XX or 47 XXY: ovotestis, ambiguous genitalia)

Question 32

5-alpha reductase deficiency

Answer 32

Autosomal recessive Unable to convert testosterone to DHT: - Children= normal internal genitalia, ambiguous external genitalia - Puberty= testosterone increase causes masculinization--> growth of external genitalia Hormones: - Normal: Testosterone/estrogen, LH may be increased

Question 33

Kallman syndrome

Answer 33

Defective migration of GnRH cells and olfactory bulb - Decreased GnRH synthesis in hypothalamus--> lack secondary sexual characteristics (all sex hormones lower) - Anosmia

Question 34

Male/female genital homologues

Answer 34

Genital tubercle: - Glans penis/Glans clitoris - Corpus cavernosum, spongiosum/ Vestibular bulbs Urogenital sinus: - Bulbourethral glands (of Cowper)/Greater vestibular glands (Bartholin) - Prostate gland/ Skene's glands Urogenital folds: - Ventral shaft of penis (urethra)/ Labia minora (vaginal vestibule) Labioscrotal swelling: - Scrotum/Labia majora