First Aid: Repro Flashcards
Effects on fetus of the following teratogens
a) ACEi
(b) Aminoglycosides (Gentamycin, Tobramycin, Amikacin
(b) Lithium
Teratogens
(a) ACEi = renal developmental abnormalities
(b) Gentamycin/tobramycin (aminoglycosides) = CN VIII abnormalities => hearing difficulty
(c) Lithium and Epstein’s anomaly = messed up tricuspid valve
Effects on fetus of the following teratogens
(a) DES
(b) Valproate
(c) Warfarin
(a) DES: vaginal clear cell adenocarcinoma, congenital Mullerian anomalies
(b) Valproate inhibits maternal folate absorption => neural tube defects
(c) Warfarin: bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities
“keep baby heppy w/ heparin”
Maternal substance abuse associated w/
(a) Placental abruption
(b) Low birth weight in fetus
Maternal substance abuse
(a) Placental absorption associated w/ cocaine
(b) Low birth weight in fetus associated w/ smoking
Thalidomide
(a) 2 indications
(b) Teratogenic effects
Thalidomide = immunomodulator
(a) Used in some malignancies (multiple myeloma) and Lyme’s disease
(b) Teratogenic = limb defects
Mechanism of ID and other abnormalities seen in fetal alcohol syndrome
Mechanism is failure of cell migration
- MR, microcephaly, facial abnormalities, limb dislocation, heart defects
- heart-lung fistulas, holoprosencephaly
Differentiate consequence of mutation in sonic hedgehog vs. hox gene
Sonic hedgehog codes anterior-posterior, while hox (homeobox) for craniocaudal direction
Sonic hedgehog mutation = holoprosencephaly (failure of prosencephalon to develop into 2 hemispheres)
Hox mutation = appendages in wrong location
Differentiate function of sonic hedgehog vs. hox gene
Sonic hedgehog patterns along anterior-posterior axis
Hox/homeobox gene patterns along craniocaudal direction
How long after fertilization do the following occur
(a) Implantation
(b) Gastrulation
(c) Organogenesis
Fertilization = day 0
(a) Fertilization –> morula –> blastula –> implants between days 6-10
(b) Gastrulation (formation of 3 layers) starts around week 3 (3 weeks, 3 layers)
(c) Organogenesis: weeks 3-8 weeks
Etiology of the VACTERL association
VACTERL association = nonrandom co-occurence of birth defects due to defect in mesoderm (all mesodermal structures)
Vertebral Anal atresia Cardiac defects TE fistula Renal defects Limb defects
Differentiate patent urachus from patent vitelline duct
Urachus (from allantois) connects yolk sac to fetal bladder, sopatent urachus => urine comes out of umbilicus
Vitelline duct connects yolk sac to midgut lumen, so patent vitelline duct = poops comes out of belly button
Complications of
(a) Urachal cyst
(b) Meckel diverticulum
(a) Urachal cyst = partial failure of urachus (attaching yolk sac to bladder) to obliterate => fluid filled cavity lined w/ uroepithelium
- can lead to infection or adenocarcinoma
(b) Meckel diverticulum = partial failure of vitelline duct (attaching yolk sac to intestinal lumen) to obliterate => true diverticulum
- can be filled w/ heterotypic gastric or pancreatic tissue => melena, hematochezia, abdominal pain
Differentiate cytotrophoblast and syncytiotrophoblast
Cytotrophoblast is the inner cell layer of the fetal side of the placenta, cytotrophoblast makes the cells
Then syncytiotrophoblast is the outer layer that secretes beta-hCG to maintain endometrial lining
Function of beta-hCG to maintain pregnancy
Beta-hCG is structurally similar to LH, so it stimulates the corpus luteum (cells leftover in ovary after ovulation) to secrete progesterone
Progesterone maintains lining
Which parts of the brachial apparatus are derived from each of the three layers?
‘CAP’
Brachial clefts from ectoderm
Brachial arches from mesoderm and neural crest
Brachial pouches from endoderm
Functions of the derivatives of the 6 brachial arches
“when at the golden arches: first chew, then smile, then swallow, the speak”
- 1st arch: CN V2 and V3, muscles of mastication for chewing
- 2nd arch: CN VII, muscles of facial expression
- 3rd arch: CN IX innervating stylopharyngess to swallow
- 4th arch: CN X (superior laryngeal branch) innervates pharyngeal constrictors for swallowing
- 6th: CN X (recurrent laryngeal branch) for intrinsic muscles of the larynx for speaking
What is unique about the nerves that innervate derivates of the brachial arches
CN V3 (arch 1), CN VII (2nd), CN IX (3rd), CN X (4 and 6) are the only cranial nerves that carry both motor and sensory components
One exception = CN V2 (only sensory, no motor) that innervates part of 1st arch
Differentiate brachial/pharyngeal touch d/o
(a) Treacher Collins
(b) DiGeorge Syndrome
CAP: brachial clefts from ectoderm, brachial arches from mesoderm, brachial pouches from endoderm
(a) Treacher collins = syndrome of the first brachial arch from failure of 1st arch neural crest cells to migrate (so mesodermal issue)
(b) DiGeorge syndrome = defect of brachial pouch (endoderm)
Treacher Collins syndrome
D/o of first brachial arch = Treacher Collins- 1st arch neural crests fail to migrate => mandibular hypoplasia and facial abnormalities
Using the embryologic derivatives of the 3rd and 4th brachial pouches, name the main features of DiGeorge syndrome
DiGeorge syndrome = aberrant development of the 3rd and 4th pouches
- 3rd pouch => inferior parathyroid and thymus
- 4th pouch => superior parathyroid glands
Thymic aplasia => T cell deficiency
No parathyroid glands = no PTH => hypocalcemia
Also associated cardiac defects = conotruncal anomalies
Paramesonephric duct
(a) Males
(b) Females
Paramesonpehric duct = Mullerian duct
(a) Degenerates in males due to MIF (mullerian inhibitory factor) produced by Sertoli cells
(b) Females (default, aka w/o MIF that won’t be present w/o testes which require SRY gene for development)- Paramesonephric duct => fallopian tubes, uterus, upper vagina
Clinical presentation of Mullerian agenesis
Mullerian agenesis = lack of devleopmnt of the paramesonephric duct
-still have ovaries, but no fallopian tube or uterus
So presents as primary amenorrhea (b/c no uterus) in female w/ fully developed secondary sex characteristics (ovaries are functional)
Mesonephric duct
(a) Males
(b) Females
Mesonephric (Wollfian) duct
(a) Males- develops ‘SEED’ = seminiferous tubules, epididmyis, ejaculatory duct, ducutus deferens
(b) Remnant in females becomes Gartner duct
Clinically what would result from lack of Mullerian inhibitor factor from Sertoli cells?
W/o MIF: paramesonpehric duct doesn’t degenerate => get female internal genitalia (fallopian tubes, uterus, upper vagina)
But still testoersone from Leydig cels => also get male internal and external genitalia
So have both male and female internal and male external genitalia
-same presentation if lack of Serotoli cells
What happens to the gubernaculum in males vs. females
Gubernaculum = band of fibrous tissue
In males the gubernaculum anchors the testes w/in the scrotum
In females the gubernaculum forms the ovarian ligament and round ligament of the uterus
LN that drain
(a) Ovaries/testes
(b) Distal vagina/scrotum
(d) Proximal vagina and uterus
(a) Ovaries and testes come from the abdominal cavity so bring their lymphatics and blood supply w/ them- drain into para-aortic LN
(b) Distal vagina and scrotum to the superficial inguinal nodes
(c) Proximal vagina and uterus to obturator, external iliac, and hypogastric nodes
Explain mechanism by which Sildenafil tx ED
Sildenafil = PDE5 inhibitor that decreases breakdown of cGMP
More cGMP (normally mediated by NO release) relaxes smooth muscle causing vasodilation and increased blood to penis
Which part of the testes makes them temperature sensitive
Sertoli cells are temperature sensitive- reduction in sperm production (b/c Sertoli cells support sperm production) and increased inhibin (inhibits FSH release) at higher temperatures
Male homolog of female granulosa cells
Granulosa cells in F are stimulated by FSH to take androgens (from theca cells) and convert into estradiol
Male homolog = Sertoli cells which are inside seminiferous tubules and support developing spermatogonia
Male homolog of female theca cells
Theca cells line peripherally to granulosa cells and are stimulated by LH to produce androgens later converted to estradiol
Male homolog = Leydig cells which lie in interstitium (instead of inside seminiferous tubules like Leydig cells) and are stimulated by LH to produce testosterone
Differentiate affect of temperature on Leydig vs. Sertoli cells
Only Sertoli cells are temperature sensitive: in response to higher temp => increased inhibin and decreased sperm production
While Leydig cells and their testosterone production are unaffected by temp
Rank by potency: type of estrogen from fat, ovary, and placenta
Estriadiol > estrione > estriol
- estradiol is produced by the ovary (in granulosa cells stimulated by FSH)
- estrione aromatized in peripheral adipose tissue
- estriol produced by placenta
4 places progesterone is produced
Progesterone production
- Corpus lutuem- what supports the pregnancy before placenta is large enough
- Placenta- takes over from corpus luteum to support the pregnancy
- Adrenal cortex- zona reticulatum
- Testes
Explain the role of progesterone in causing lactation
Progesterone produced by placenta, after delivery (bye bye placenta) there is a loss of the progesterone inhibition on prolactin
So prolactin rises and stimulates lactation
Which phase of the menstrual cycle varies in length?
Follicular phase (proliferative) can vary in length, while the luteal phase (secretory) is always just 14 days
So if you have 40 day cycle, follicular phase is super long while luteal phase is still the same 2 weeks
-this is b/c after ovulation the corpus luteum only a certain amount of time before regressing and therefore removing progesterone
What causes menstruation?
Corpus luteum regresses => no more progesterone => endometrial cells no longer stabilized
Apoptosis of endometrial cells => shedding = menstruation
MC location of egg fertilization
(a) How many days after ovulation
Egg MC fertilized (a) 1 day after ovulation) in the ampulla (upper end) of the fallopian tube
What part of the placenta secretes beta-hCG?
(a) When does this become detectable in blood vs. urine
Syncytiotrophoblasts (outer lining) of placenta forms beta-hCG
(a) Detectable in blood 1 week after conception, detectable on home test in urine 2 weeks after conception
Contrast role of prolactin and oxytocin in lactation
Prolactin stimulates milk production
Oxytocin assists in milk letdown (also promotes uterine contraction for labor)
Breast milk
(a) Baby requires what supplementation?
(b) Benefit to mother
Breast milk
(a) Exclusively breast fed babies require vitamin D supplementation
(b) Reduced risk of breast and ovarian carcinoma
Explain the function of beta-hCG from the syncytiotrophoblasts
beta-hCG looks like LH (same alpha subunit, diff beta subunit which is why we test for beta), LH needed to maintain the corpus luteum to produce progesterone for first 8-10 weeks of pregnancy
B/c only until 8-10 weeks is placenta mature enough to synthesize its own estriol and progesterone, then corpus luteum degenerates
Conditions of
(a) High hCG
(b) Low HCG
(a) High hCG seen in multiple gestations (twins), hydatidiform mole (just placenta tissue), choriocarcinoma, Down syndrome
(b) Low hCG: ectopic/failing pregnancies (not functional placenta), Edward and Patau syndrome
Clinical presentation of premature ovarian failure
Premature ovarian failure presents as menopause before the age of 40
B/c menopause is physiologically due to reduced estrogen from age-related decline in number of ovarian follicles, if premature failure of these follicles => menopause before that age-related decline
What forms the blood-testis barrier
(a) Fxn
Blood-testes barrier formed by tight junctions btwn adjacent Sertoli cells (sertoli cells are within the seminiferous tubules)
(a) Fxn = isolate from autoimmune attack or infection
Differentiate location of production and potency of the three male androgens
Testosterone and DHT made in the testis, while androstenedione is produced in the adrenal cortex
DHT most potent, then T, then androstenedione
How can exogenous testosterone cause infertility
Exogenous testosterone inhibits HPA axis => reduced intratesticular production of testosterone => reduced testicular size and activity => azoospermia
How may aromatase deficiency present during pregnancy?
Aromatase deficiency = can’t convert androgens into estrogen => get masculinization (ambiguous genitalia) of female infants
Elevated fetal androgens can cross placenta and cause maternal virilization during pregnancy
Clinical presentation of androgen insensitivity syndrome in (46,XY)
(a) Lab values
Normal-appearing females, female external genitalia but uterus and fallopian tubes absent (b/c MIF present)
-develop testes
(a) Elevated testosterone, estrogen, and LH
18 pre-pubertal boy p/w anosmia- dx?
Kallmann syndrome = form of hypogonadotropic hypogonadism due to defective migration of GnRH cells and defective formation of olfactory bulb => reduced GnRH secretion (causing failure to complete puberty in both M and F) and anosmia
Reduced GnRH, FSH, and LH
Infertility 2/2 low sperm count in males and amenorrhea in F
Tx of gestational HTN
Antihypertensives safe during pregnancy: alpha-methyldopa, labetolol, hydralazine, nifedipine
Deliver at 37-39 weeks
Tx of preeclampsia
Preeclampsia: tx w/ antihypertensives and IV Mg to prevent seizures
Only definitive therapy is delivery of fetus
Tx of eclampsia
Eclampsia = preeclampsia and seizures
IV magnesium sulfate
- antihypertensives
- ***immediate delivery (can’t wait at this point)
Why is delivery necessary to treat eclampsia
Once mother has preeclampsia plus seizures the fetus needs to be delivered 2/2 risk of maternal death due to stroke, intracranial hemorrhage, or ARDS
HELLP
(a) What does it stand for?
(b) Cause
(c) Blood smear finding
(d) Tx
HELLP
(a) hemolysis, elevated liver enzymes, and low platelets
(b) Manifestation of severe preeclampsia
(b) Schistocytes on smear- b/c microvascular clots sheer RBC
(d) Tx = immediate delivery
Preeclampsia definition
(a) Cause
Preeclampsia = new onset HTN w/ either proteinuria or end-organ dysfunction after 20th week of gestation
(a) Caused by a problem w/ the placenta, it’s the placenta causing the HTN
Abnormal placental spiral arteries => endothelial dysfunction, vasoconstriction, ischemia
Complications of preeclampsia
Complications: placental abruption coagulopathy renal failure uteroplacental insufficiency eclampsia
Why is preeclampsia defined as new-onset HTN after 20th week, what about before?
Before 20th week if new-onset HTN w/ either proteinuria or end-organ dysfunction arises, it suggests molar pregnancy
Define gestational HTN
BP over 140/90 for the first time after 20th week of gestation
- no preexisting HTN
- no proteinuria or end organ damage (or else it’s preeclampsia instead)
Mothers w/ increased risk of preelampsia
Pre-existing HTN, diabetes, chronic renal disease, autoimmune d/o
RF for ectopic pregnancy
RF for ectopic pregnancy = fallopian tube scarring
-h/o PID or prior tubal surgery
Endometrial, cervical, ovarian cancers
(a) Rank by incidence in the US
(b) Rank by prognosis
(a) Incidence: endometrial MC, then ovarian, then cervical (more common worldwide w/o screening and HPV vaccine)
(b) Ovarian has worst prognosis, then cervical, endometrial has best
Two medication options for pts w/ PCOS who desire pregnancy
Induce ovulation w/ clomiphene citrate
Usually put on OCPs to reduce symptoms but not if desire pregnancy…
Which ovarian neoplasm associated w/
(a) Psammoma bodies
(b) Pseudomyxoma peritonei
Ovarian neoplasm
(a) Psammoma bodies seen in serous cystadenocarcinoma (serous surface epithelial tumor)- MC ovarian neoplasm
(b) Pseudomyxoma peritonei (intraperitoneal mucus accumulation ‘jelly belly’) associated w/ mucinous cystadenocarcinoma
Germ cell choriocarcinoma- composition
(a) Why may present w/ hemoptysis/SOB
Germ cell choriocarcinoma = malignancy of trophoblastic tissue (cytotrophoblasts and synctiotrophoblasts) but NO chorionic villi!!! (so just the trophoblast tissue, no villi)
(a) Placenta tissue is made to invade BVs, so quickly hematogenously spreads and often to lungs => SOB and hemoptysis
Tx options for adenomysosis
Adenomyosis = extension of glandular endometrial tissue into the uterine myometrium
Tx include GnRH agonists (disrupt pulsatile GnRH) or hysterectomy
Intraductal papilloma
(a) Association w/ cancer
(b) Typical location
(c) Clinical presentation
Intraductal papilloma
(a) Benign itself but slight (1.5-2x) increased in risk for carcinoma
(b) Small tumor of the lactiferous ducts, typically beneath the areola
(c) Serous or bloody nipple discharge
Name some drugs that can cause gynecomastia
Spironolactone, ketoconazole
B/c gynecomastia (breast enlargement in males) is due to high estrogen, both these drugs inhibit steroid (androgen) synthesis
Which sympathetic-acting drug can be used to tx priapism
Intracavernosal phenylephrine (selective alpha1 agonist) for vasoconstriction
Testosterone levels in b/l vs. unilateral cryptorchidism
T reduced in b/l, but normal in unilateral since Leydig cells are unaffected by temperature
Varicocele
(a) Etiology
(b) Why left sided
(c) Physical exam finding
Varicocele = MC cause of scrotal enlargement in adult males
(a) Dilated veins in pampiniform plexus due to increased venous pressure
(b) 2/2 increased resistance of flow from L gonadal vein into the L renal vein (it’s at a right angle)
(c) ‘Bag of worms’ on palpation
MC location of extragonadal germ cell tumor
Can arise midline, MC sacrococcygeal teratomas in children/infants
2 RF for testicular germ cell tumors
- Cryptorchidism (testes in abdomen 2/2 failure to descend)
2. Klinefelter syndrome
MC testicular tumor
(a) Histologic appearance
(b) Serum marker
(c) Prognosis
95% testicular tumors are germ cell tumors, and MC germ cell tumor = seminoma
(a) Fried egg appearance appearance: large cells in lobules w/ watery cytoplasm
(b) Elevated alk phos
(c) Excellent prognosis, late mets
Teratomas in M vs. F
Mature teratomas in females aren’t malignant, while they can be malignant in adult males
-still benign in male children
Drugs to treat androgenic symptoms of PCOS
- Ketoconazole inhibits 17,20 desmolase to inhibit steroid synthesis
- Spironolactone inhibits steroid binding and synthesis
How do OCPs prevent pregnancy?
OCPs provide exogenous hromones => inhibit release of LH/FSH
No estrogen surge = no LH peak = no ovulation, no ovluation of eggs = can’t get preggers!
Contraindications to OCPs
Smokers over 35 (2/2 risk of caridovascular events)
H/o stroke or thromboembolic events
H/o estrogen-dependent tumor
How does tamsulosin exert selective effects
Tamsulosin specifically inhibits alpha1 receptors on the prostate to inhibit smooth muscle contraction, while not inhibiting alpha1 receptors on vasculature (therefore not causing vasodilation peripherally)
Mechanism of minoxidil
Minoxidil = direct arteriolar vasodilator
Applied topically for androgenetic alopecia, systemically for severe refractory HTN
Rogaine vs. propecia
Rogaine = minoxidil for androgenetic alopecia, works by direct arteriolar vasodilation
Propecia = Finesteride = 5alpha reductase inhibitor to reduce T to DHT
