Embryology and Devo Flashcards
Found at base of limbs. Anterior-posterior and CNS development. Mutation leads to holoprosencephaly
Sonic hedgehog gene
Produced at apical end of limbs at ectodermal ridge. Needed for dorsal-ventral axis organization.
Wnt-7
Produced at apical ectodermal ridge. Stimulates mitosis of mesoderm.
FGF
Segmental organization from cranium to caudum. Mutations cause appendages in wrong locations.
Hox
Codes for transcription factors
Hox
Which week does bilaminar disc (epiblast, hypoblast) form
Week 2
Gastrulation occurs
Week 3
Endoderm, mesoderm and ectoderm arise from
Epiblast primitive streak
Notochord arises from
Midline mesoderm
Neural plate arises from
Overlying ectoderm
Beginning of organogenesis and increased susceptibility to teratogens
Weeks 3-8
Ultrasound can see fetal heartbeat by
Week 6
Male female genitalia can be distinguished by
Week 10
Bones of skull are derived from
Neural crest
C cells of thyroid, chromaffin cells of adrenal medulla, melanocytes, pia and arachnoid, aorticopulmonary septum and endocardial cushions are derived from
Neural crest
Autonomic ganglia, DRG, cranial nerves and Schwann cells are derived from
Neural crest
Anal canal below pectinate, parotid, sweat and mammary glands, anterior pituitary lens of eye are derived from
Surface ectoderm
What induces formation of neuroectoderm (neural plate)
Notochord
Upper vagina, lymphatics, spleen, peritoneum, wall of gut tube, are derived from
mesoderm
Gut tube epithelium, most of urethra and lower vagina, lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells derived from
Endoderm
When does malformation occur
Weeks 3-8
A woman with vaginal clear cell adenocarcinoma or abnormal uterus likely had mother who consumed
Diethylstilbestrol
Absence of skin from the scalp is suggestive of which teratogen
Methimazole
Discolored teeth, inhibited bone growth suggest maternal use of
Tetracycline
Thalidomide use to tx leprosy or MM increases risk of what in fetus
Limb defects (“flipper” limbs)
Warfarin can cause what in fetus
bone deformities, fetal hemorrhage, abortion, olpthalmologic abnormalities
Can cause placental abruption, low birth weight, preterm birth, IUGR
Cocaine
Low birth weight, preterm labor, SIDS can occur due to maternal use of
cigarettes (smoking)
Cretinism results from
Lack or excess Iodine in maternal diet
Anal atresia to sirenomelia, congenital heart defects, neural tube defects and macrosomia are consequences of which maternal condition
Diabetes
Swofrdfish, shark, tilefish and king mackerel consumption increase risk of neurotoxicity in fetus due to
methylmercury
Fetal alcohol syndrome occurs due to failure of
Migration
Smooth philtrum, thin upper lip (vermilion border), small palpebral fissures (eye openings) and low set ears in baby indicate
Fetal alcohol syndrome
First to differentiate after fertilization
Trophoblast
Secretes beta-hCG after implantation
Synctiotrophoblast
Trophoblastic layer that facilitates exchange of nutrients and waste between mother and fetus
Synctiotrophoblast
Function of hCG
Maintain progesterone and sustain pregnancy
Failure of trophoblast to invade endometrium adequately can lead to
Pre-eclampsia
Dizygotic twins result from
2 separate eggs fertilized by two separate sperm (dichorionic, diamniotic)
What is the chorion
Outer layer of amniotic sac that attaches to endometrium and allows nutrient exchange between fetus and mother
What is the amnion
Inner layer of amniotic sac that protects developing fetus
Monozygotic twins that have two separate chorion and two separate amnion likely arose from
Cleavage at 2-cell stage
Monozygotic twins that share a chorion and have two separate amnion likely arose from
Cleave at morula stage (4-8 days)
Monozygotic twins that share one chorion and one placenta likely arose from
Blastocyst stage cleavage (8-12 days)
Conjoined twins result due to cleavage at which stage
> 13 days, formed embryonic disc
Monozygotic twins most commonly occur due to cleavage of
Morula (one chorion, two amnion)
Leading cause of intellectual disability in the US
Fetal alcohol syndrome
Inner layer of chorionic villi that produces cells
Cytotrophoblast
Outer layer of chorionic villi that synthesizes hCG stimulate progesterone secretion from corpus luteum during first semester. Lacks MHC I so will not be attacked by maternal immune system
Synctiotrophoblasts
Umbilical arteries and umbilical vein are derivatives of
allantois
How many umbilical arteries and veins
2 umbilical arteries (carry deoxygenated blood from fetus to mother), 1 umbilical vein (carry oxygenated blood from mother to fetal IVC)
Urine from umbilicus indicates
Patent urachus
Urachus is derived from
Allantois
Fluid-filled cavity between umbilicus and bladder that can lead to infection or adenocarcinoma
Urachal cyst (partial failure of urachus to obliterate)
Outpouching of bladder
Vesicourachal diverticulum (slight failure of urachus to obliterate)
Congenital persistence of urachus occurs due to errors in which week of devo?
3rd week
Meconium discharge from umbilicus
Vitelline fistula (vitelline duct fails to close)
Melena (dark poop with blood), hematochezia (vomit with blood), and abdominal pain in child. Tissue biopsy presents gastric or pancreatic tissue.
Meckel diverticulum (partial closure of vitelline duct)
Congenital persistence of vitelline duct (connects yolk sac to midgut lumen) occurs due to error in which week of devo?
7th week
Nerve associated with 1st arch
CN V2 and V3
Muscles associated with 1st arch
Muscles of mastication (Temporalis, masseter, anterior digastric, tympani)
Bones associated with 1st arch
Zygoma, Maxillary process, mandibular process, malleus and incus
Ectoderm associated with 1st arch
External auditory meatus
CN associated with 2nd arch
VII (Facial)
Muscles associated with 2nd arch
Muscles of facial expression, stapedius, stylohyoid
Bones associated with 2nd arch
Stapes, stylohyoid, lesser horn of hyoid, stylohyoid ligament
Artery associated with 1st arch
Maxillary artery (of ECA)
Artery associated with 2nd arch (
Stapedial and hyoid arteries
Lateral neck mass that doesn’t move upon swallowing is remnant of
Temporary cervical sinus of branchial clefts 2-4
Failure of NC derivatives of 1st and 2nd arches (deafness, micrognathia)
Treacher-Collins syndrome
Small jaw, glossoptosis, cleft palate, airway obstruction suggest
Pierre Robin Sequence (abnormal 1st and 2nd arch development)
Superior laryngeal nerve (swallowing) is derivative of which arch
4th
Aortic arch and proximal SCA are derivatives of which arch
4
Common carotid and proximal ICA are derivatives of which arch
3
CN IX is derivative of which arch
3
CN X is part of which arch
4 and 6
Recurrent laryngeal nerve (voice) is part of which arch
6
L: Proximal pulmonary artery and ductus arteriosus are part of which arch
6
Superior parathyroids are derived from which pouch
dorsal 4th
C cells of thyroid are derived from which pouch
Ventral 4th
Thymus is derived from which pouch
Ventral 3rd
Inferior parathyroids are derived from which pouch
Dorsal 3rd
Epithelial lining of palatine tonsils are derived from
2nd pouch
Middle ear, eustachian tube and mastoid air cells are derived from
1st branchial pouch
Clefts, Arches and Pouches represent which embryologic layers respectively
Ectoderm, mesoderm, endoderm
Lower portion of vagina develops from
Urogenital sinus
Failure of fusion of maxillary and medial nasal processes
Cleft lip
Failure of fusion of lateral palatine shelves
Cleft palate
Failure of fusion of lateral palatine shelves with nasal septum
Cleft Palate
Failure of fusion of lateral palatine shelves with median palatine shelf
Cleft palate
Mesonephros develops into
Ureter, epididymis and vas deference
Fallopian tubes, uterus and upper portion of vagina are derived from
paramesonephric duct
Mayer-Rokitansky-Kuster-Hauser syndrome is
Failure of Mullerian (paramesonephric) duct development. Primary amenorrhea in woman with secondary sexual characteristics
Seminal vesicles, epididymis, ejaculatory duct, ductus deferens (SEED) derived from
Mesonephric ducts
What is the Gartner duct
Remnant of mesonephric duct in females
Decreased fertility (woman has difficulty getting pregnant) due to a resorption defect of Mullerian duct implies
Septate uterus
Incomplete failure of Mullerian ducts
Bicornuate uterus
Presents with recurrent miscarriages and multiple UTIs
Bicornuate uterus
Complete failure of Mullerian ducts
Uterus didelphys
Prostate gland arises from
Urogenital sinus
Hormone that induces development of female external genitalia
Estrogen
Hormone that induces formation of male external genitalia
DHT
failure of urethral folds to fuse. Associated with inguinal hernia and cryptorchidism
Hypospadias
Faulty positioning of genital tubercle. Associated with exstrophy of bladder
Epispadias
Anchors testes to scrotum
Gubernaculum
Forms tunica vaginalis
Processus vaginalus
Forms ovarian ligament and round ligament of uterus
Gubernaculum
Why are left varicoceles more common than right ones
Left spermatic vein enters left renal vein at 90 degree angle so there is more turbulent flow so greater pressure
Lymphatic drainage of superior bladder, cervix and body of uterus
External iliac
Lymph drainage of ovaries and testes
para-aortic
Lymph drainage of distal vaginal/vulva/scrotum/distal anus
superficial inguinal
Lymph drainage of glans penis
Deep inguinal
Lymph drainage of prostate, cervix, corpus cavernosum, proximal vagina
internal iliac
Which vessels are ligated during oophorectomy to avoid bleeding?
Ovarian vessels in Infundibulopelvic ligament (suspensory ligament of ovary)
Infundibulopelvic ligament (suspensory ligament of ovary)
Connects ovaries to lateral pelvic wall
Which structure is at risk of injury during ligation of ovarian vessels?
Ureter
Cardinal ligament
Connects cervix to side wall of pelvis
Which vessels are contained by cardinal ligament
Uterine vessels
Which structure is at risk of injury during ligation of uterine vessels
Ureter
Round ligament of uterus
Connects uterine fundus to labia majora
What is the artery of Sampson
Anastamoses between ovarian and uterine vessels. Runs under Round ligament of Uterus
Broad ligament
connects uterus, fallopian tubes, and ovaries to pelvic side wall
Ovaries, fallopian tubes, round ligaments of uterus are contained in
Broad ligament
Ovarian ligament
Connects medial pole of ovary to lateral uterus
Pathway of sperm ejaculation (SEVEN UP)
Seminiferous tubules –> Epididymis –> Vas deferens –> Ejaculatory ducts –> Nothing –> Urethra –> Penis
In a perineal straddle injury, which fascia is torn
Deep fascia of Buck
In perineal straddle injury, where does urine escape into
superficial perineal space
Posterior urethral injury where urine leaks into retropubic space occurs due to
Pelvic fractures
Anterior urethral injuries occur due to
Straddle-type falls
Erection occurs due to
PSNS of pelvic nerve: NO–> cGMP–> vasodilation
Emission occurs due to
SNS of hypogastric nerve: NE –> intracellular Ca+2–> smooth muscle contraction–> anti-erectile
Ejaculation occurs due to
visceral and somatic nerves of pudendal nerve
Granulosa cell male homolog
Sertoli cell
Theca cell male homolog
Leydig cell
Sertoli cells regulate spermatogenesis in response to
FSH
Sertoli cells secrete Inhibin B to
Inhibit FSH secretion
Leydig cells secrete testosterone in response to
LH
Carry aromatase to convert testosterone and androstendione to estrogen
Sertoli cells
Form blood testis barrier
Sertoli cells
Why do varicoceles lead to low sperm count?
Sertoli cells need cool temperatures to function
When in process of sperm become haploid?
After meiosis I (secondary spermatocyte)
What disinhibts lactation
drop in progesterone and estrogen after labor
Appearance of breast bud indicates which stage of Tanner
Tanner Stage 2, thelarche
Testicular enlargement begins in which Tanner Stage
2
Breast “mound on mound” describes which Tanner stage?
Stage IV
Penis size and length begins to increase in which Tanner stage
III
Pines width/glans starts to increase in which stage?
Stage IV
Define APGAR
Appearance (blue or pink 0-2) Pulse (0 - >100; 0-2) Grimace (Cry and pull; 0-2) Activity (movement; 0-2) Respiration (strength of cry and breath; 0-2)
Hormonal changes in menopause
Increased FSH/LH ratio, decreased estrogen, increased GnRH
Amennorrhea for 12 months, decreased estrogen production, preceded by abnormal cycles for 4-5 years
Menopause
Spike in which hormone levels is specific for Menopause?
FSH spike (due to loss of negative feedback due to decreased estrogen)
hCG levels in ectopic/failing pregnancy, Edward syndrome and Patau syndrome
decreased
hCG levels in hyatidiform moles, choriocarcinomas and Down syndrome
Increased
Where is estrone produced
Adipose tissue via aromatase
Where is estradiol produced
Ovary (primary follicles)
Where is estriol produced
Placenta (pregnancy)
Where are estrogen receptors expressed
Cytoplasm, translocate to nucleus when bound
Stimulates endometrial gland secretions, spiral artery development, maintenance of pregnancy, decreases myometrial excitability, produces thick cervical mucus to trap sperm, increases body temperature, inhibits FSH and LH, prevents contractions, decreases ER expression, prevents endometrial hyperplasia
Progesterone
Development of female sexual characteristics, female fat distribution, bone growth, follicle growth, increases myometrial excitability, upregulates ER, FSH, LH receptors, inhibition of FSH and LH and then LH surge, increases HDL, decreases LDL
Estrogen
Young female presenting with unilateral painful cystic lesion along vaginal canal that produces mucus-like fluid likely has
Bartholin cyst
3 places that HPV infects and how it appears
Vulva (genital warts 6 + 11), Vaginal canal, Cervix (16, 18, 31, 33); biopsy shows koilocytes (cells with raisin-like nuclei)
How to classify low-risk vs high-risk HPV
DNA sequencing
“Paper thin epidermis” with fibrosed or thickened dermis that presents as white patch (leukoplakia) in post-menopausal woman is
Lichen sclerosis (slight risk of squamous cell carcinoma)
Leukoplakia with thick leathery vulvar skin is
Lichen simplex chronicus (no risk of squamous cell carcinoma)
Which three conditions present with vulvar leukoplakia?
Lichens sclerosis, Lechen simplex chronicus, Vulvar carcinoma
Woman who develops vulvar carcinoma in her 40s-50s likely was infected by
HPV 16, 18, 31, 33
Woman who develops vulvar carcinoma in her 70s
non-HPV related
Characterized by malignant epithelial cells in epidermis of vulva; presents as erythematous, pruritic, ulcerated vulvar skin
Extramammary Paget disease
PAS+, keratin+ and S100-
Paget disease
PAS-, Keratin-, S100+
Melanoma
What is PAS a marker for?
Mucus (only epithelial cells make mucus)
Important distinction between Paget disease of nipple vs vulva
Paget disease of nipple suggests cancer of breast. Paget dz of vulva does not indicate cancer
Early in development, upper 2/3 of vagina and lower 1/3 of vagina are composed of
Upper: columnar epithelium
Lower: non-keratinizing squamous
Persistance of columnar epithelium in upper vagina is tied to which teratogen
Maternal use of DES– vaginal adenosis
“Grape like mass” protruding from vagina of 5yo girl is a malignant proliferation of what tissue
Mesenchyme, immature skeletal muscle
Desmin and myogenin staining confirm
Embryonal rhabdomyosarcoma
Lymph node spread of lower 1/3 vagina carcinoma
Superficial inguinal
Lymph node spread of upper 2/3 vagina carcinoma
Iliac nodes
Which part of cervix is most susceptible to HPV infection?
Transformation zone (point between endocervix and exocervix)
HPV E6 protein function
Destroys p53
HPV E7 protein function
destroys Rb
90% of HPV is cleared by body. T/F?
True
What are the four defining features of Cervical Intraepithelial neoplasia?
Koilocytic change, nuclear atypia, disordered cellular maturation, increased mitotic activity within cervical epithelium
Key feature of invasive carcinoma
Dysplasia goes through basement membrane
Most common type of cervical carcinoma
Squamous cell (80%)
Why is postrenal failure the most common cause of death in women with cervical carcinoma?
Cancer can invade anterior wall and into bladder, block ureters, causing hydronephrosis and lead to postrenal failure
Screening test and confirmatory test for cervical cancer
Pap smear for screen, colposcopy for confirmation
HPV vaccine has antibodies against which strains?
6, 11, 16, 18
A woman who develops amenorrhea after a D&C likely lost which cells
Basalis (regenerative layer of endometrium)– Asherman syndrome
What are anovulatory cycles
Estrogen-driven proliferation phases without progesterone-driven secretory phases–> lead to abnormal cycles, heavy bleeding due to excessive endometrial growth
More common in menarche and menopause due changes in HPA
What is the histologic diagnostic cell for chronic endometritis
Presence of plasma cells
Why can Tamoxifen cause endometrial polyps?
Though it has anti-estrogenic effects on breast, has pro-estrogenic effects on endometrium
Pain during menstruation, pelvic pain, and potential infertility can be caused by
Endometriosis
Most common site of endometriosis
Ovary
What is endometriosis?
Ectopic location of endometrial tissue and glands outside of uterus. Could be due to retrograde menstruation, abnormal development of Mullerian duct or lymphatic dissemination
Postmenopausal bleeding in a woman with PCOS, obesity or HRT is likely due to
Endometrial hyperplasia from unopposed estrogen
In a woman with postmenopausal bleeding, what is the most important indicator for progression to endometrial carcinoma?
Cellular atypia
Three tumors that produce psammoma bodies
Mengingeomas, mesothelioma, papillary carcinoma of thyroid, Endometrial carcinoma serous type
Two most common type of surface epithelial ovarian tumors
Serous and mucinous
Single simple cyst with flat lining in woman in her 30s-40s suggests
Cyst adenoma (benign ovarian tumor)
Complex cysts with thick, shaggy lining in postmenopausal woman. Bilaterality, suggests
Malignant cystadenocarcinoma
Which type of ovarian carcinoma is increased in pts with BRCA1
Serous cystadenocarcinoma of ovary and fallopian tube
Ovarian tumor with bladder-like (urothelial) epithlium is
Brenner tumor, usually benign
Serum marker for surface epithelial ovarian tumor to monitor treatment
CA-125
A 20-30 woman presenting with symptoms of hyperthyroidism and elevated thyroid levels but normal thyroid gland likely has
R Unilateral Teratoma
Most common immature tissue in teratoma with malignant potential
Neural ectoderm
Woman presenting with ovarian tumor, pleural effusion and ascites has
Fibroma Meigs syndrome (resolves with removal of tumor)
Krukenberg tumor (Bilateral mets to ovary) is commonly from
Diffuse type gastric carcinoma (Signet cells)
Pseudomyxoma peritonei mets to ovary likely originated in; presentation is “jelly belly” due to massive production of mucus in peritoneum
appendix
What does third-trimester bleeding suggest
Placenta previa; requires CS
Third trimester bleeding, painful contractions and fetal insufficiency suggest
Placental abruption (separation of placenta from decidua); common cause of stillbirth
Presents with difficult delivery (delayed) of placenta and excessive postpartum bleeding (risk of hemorrhage)
Placenta accreta (implantation of placenta into myometrium)
A woman with placenta accreta often requires
Hysterectomy
Woman presenting with hypertension, proteinuria and edema in the third trimester (> 20 weeks) of pregnancy likely has
Pre-eclampsia
Mechanism that causes pre-eclampsia
Decreased organ perfusion between placenta and uterus, leading to vasospasm and endothelial activation
Best way to resolve preeclampsia
Deliver baby
Define HELLP syndrome
Hemolysis, Elevated Liver enzymes, Low Platelets
Preeclampsia with thrombotic microangiopathy involving liver
What is Eclampsia
Preeclampsia + seizures
Uteroplacental ischemia–> oxidative stress–> activation of secondary mediators–>endothelial dysfunction, vasospasm, activation of coagulation-> widespread vasoconstriction–> hypoxic/ischemic damage to vascular beds is pathophysiology of
Preeclampsia
What is seizure prophylaxis in a woman with preeclampsia
Magnesium sulfate
How to reverse magnesium sulfate toxicity
Calcium gluconate
Normal ovum fertilized by two sperm (or one that duplicates itself); 69 chromosomes
Partial mole
Empty ovum fertilized by two sperm; 46 chromosomes
Complete mole
Fetal tissue is present
Partial mole
Fetal tissue is absent
Complete mole
Some villi are hydropic, some are normal
Partial mole
Most villi are hydropic (edematous)
Complete mole
Focal proliferation of trophoblast
Partial mole
Complete proliferation of trophoblast (“snowstorm” on US)
Complete mole
Risk for choriocarcinoma is minimal
Partial mole
Risk for choriocarcinoma is increased
Complete mole
What are the two defining features of molar pregnancy
Uterus expands as pregnancy progresses but uterus is much larger than expected and beta-hCG is higher than expected for date of gestation
When and how does molar pregnancy classically present in a woman without prenatal care?
Second trimester as passage of grape-like masses
When and how is molar pregnancy diagnosed in woman with prenatal care
1st trimester via US; absent fetal heart sounds and “snowstorm” appearance
Choriocarcinoma from gestation vs choriocarcinoma from GCT
Gestational responds to chemotherapy, GCT does not
Woman who presents with elevated beta-hCG, shortness of breath, hemoptysis after giving birth may have
gestational choriocarcinoma
Risk factors for placental abruption
Smoking, trauma, hypertension, preeclampsia and cocaine abuse
4 Ts of postpartum hemorrhage
aTony, Trauma, Thrombin (coagulopathy), Tissue (retained prodcuts of conception)
Too little amniotic fluid due to fetal inability to “pee”
Oligohydramnios (can cause Potter sequence)
Too much amniotic fluid due to fetal inability to “swallow”
Polyhydramnios
Hypertension <20 weeks of pregnancy suggests
Molar pregnancy
Which phospholipid ratio assesses lung maturity/surfactant production?
Lecithin(dipalmitoylphosphatidylcholine)/sphingomyelin (>2 = mature)