Reproductive - First Aid Flashcards
Sonic hedgehog gene is produced at the…
base of the limbs in the zone of polarizing activity.
Sonic hedgehog gene is involved in..
patterning along the anterior posterior axis and CNS development.
Mutation of the sonic hedgehog gene can cause….
holoprosencephaly.
The Wnt-7 gene is produced at…
the apical ectodermal ridge (a thickened ectoderm at the distal end of each developing limb.
Wnt-7 gene is necessary for…
proper organization along the dorsal-ventral axis.
FGF gene is produced at the….
apical ectodermal ridge.
FGF gene stimulates….
mitotis of the underlying mesoderm providing for lengthening of limbs.
Homeobox (Hox) gene is involved in…
segmental organization of the embryo in a craniocaudlal direction.
Hox mutations lead to…
appendages in the wrong locations.
Day 0 of fetal development
fertilization by sperm, forming zygote, initiating embryogenesis
Fetal development within one week
hCG secretion begins around the time of implantation of the blastocyst
Fetal development within 2 weeks
bilaminar disc (epiblast, hypoblast) (2 weeks = 2 layers)
Fetal development within 3 weeks
trilaminar disc (3 wks = 3 layers) gastrulation primitive streak, notochord, mesoderm, neural plate begin to form
Fetal development during wks 3-8 (embryonic period)
neural tube formed by neuroectoderm and closes by wk 4; organogenesis **extremely susceptible to teratogens
Fetal development within within wk 4
heart begins to beat upper and lower limb buds (week 4 = 4 chambers, 4 limbs)
Fetal development within week 6
fetal cardiac activity is visible by transvaginal ultrasound
Fetal development within week 10
genitalia have male/female characteristics
Gastrulation is the process that…
forms the trilaminar embryonic disc. It establishes the ectoderm, mesoderm and endoderm germ layers.
Gastrulation starts with the….
epiblast invaginating to form the primitve streak.
Surface ectoderm derivatives (8)
-adenohypophysis -lens of eye -epithelial linings of oral -sensory organs of the ear -olfactory epithelium -epidermis -anal canal below pectinate line -parotid, sweat and mammary glands
A craniopharyngioma is…
a benign Rathke pouch tumor with cholesterol crystals and calcifications. (surface ectoderm derivative)
Neuroectoderm derivatives (3)
-brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland) -retina and optic nerve -spinal cord
Neural Crest derivatives (8)
-PNS (DRG, cranial nerves, celiac ganglion, Schwann cells, ANS) -melanocytes, -chromaffin cells of adrenal medulla -parafollicular cells of thyroid -pia and arachonid -bones of the skull -odontoblasts -aorticopulmonary septum
Mesoderm derivatives (15)
-muscle -bone -CT -serous linings -spleen -CV structures -lymphatics -blood -wall of gut tube -vagina -kidneys -adrenal cortex -dermis -testes -ovaries
Mesodermal defects =
VACTERL -Vertebral defects -Anal atresia -Cardiac defects -Tracheo-Esophageal fistula -Renal defects -Limb defects
Endoderm derivatives
-gut tube epithelium -most of urethra -luminal epithelial derivatives (lung, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid)
Agenesis
absent organ due to absent primordial tissue
Aplasia
absent organ despite presence of primordial tissue
Hypoplasia
incomplete organ development; primordial tissue present
Deformation
extrinsic disruption; occurs after the embryonic period
Disruption
secondary breakdown of a previously normal tissue (ex. amniotic band syndrome)
Malformation
intrinsic disruption; occurs during the embryonic period
Sequence
abnormalities result from a single primary embryological event
Before week 3, teratogens cause…
all-or-none effects.
After week 8, teratogens affect…
growth and function.
ACE Inhibitors cause…
renal damage.
Alkylating agents cause…
absence of digits
Aminoglycosides cause…
CN VIII toxicity
Carbamazepine causes…
neural tube defects*** craniofacial defects fingernail hypoplasia developmental delay IUGR
Diethylstilbestrol (DES) causes…
vaginal clear cell adenocarcinoma congenital Mullerian anomalies
Folate antagonists cause…
neural tube defects
Lithium causes…
ebstein anomaly (atrialized right ventricle)
Methimazole causes…
aplasia cutis congenita
Phenytoin causes…
Fetal hydantoin syndrome (microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR and intellectual disability)
Tetracyclines cause…
discolored teeth
Thalidomide causes…
limb defects (phocomelia, micromelia)
Valproate causes…
inhibition of maternal folate absorption leading to neural tube defects
Warfarin causes…
bone deformities, fetal hemorrhage, abortion, and ophthalmologic abnormalities
Cocaine causes…
abnormal fetal growth and fetal addiction; placental abruption.
Smoking (nicotine, CO) causes…
low birth weight, preterm labor, placental problems, IUGR, and ADHD.
Iodine (lack or excess) causes…
congenital goiter or hypothyroidism (cretinism)
Maternal diabetes causes…
caudal regression syndrome (anal atreisa to sirenomelia), congenital heart defects and neural tube defects.
Excess vitamin A causes…
extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac abnormalities).
X-rays cause…
microcephaly and intellectual disability.
Congenital malformations (7) of Fetal Alcohol Syndrome include…
intellectual disability developmental retardation microcephaly holoprosencephaly facial abnormalities limb dislocation heart defects
Facial abnormalities of FAS include…
smooth philtrum, thin upper lip, small palpebral fissures and hypertelorism.
Dizygotic twins arise from…
2 eggs that are separately fertilized by 2 different sperm and will have 2 separate amniotic sacs and 2 separate placentas.
Monozygotic twins arise from…
1 fertilized egg that splits into 2 zygotes early in pregnancy.
The degree of separation between monozygotic twins depends on…
when the fertilized egg splits into 2 zygotes. the timing of this separation determines the number of chorions (placentas) and amnions.
Fetal components of the Placenta
-cytotrophoblast -syncytiotrophoblast
Maternal component of the placenta
decidua basalis
The cytotrophoblas is the…
inner layer of chorionic villi that makes cells.
The syncytiotrophoblast is the…
outer layer of chorionic villi that secretes hCG.
The decidua basalis is derived from the…
endometrium and has maternal blood in lacunae.
The umbilical arteries (2) return…
deoxygenated blood from the fetal internal iliac arteries to the placenta.
The umbilical vein (1) supplies…
oxygenated blood from the placenta to the fetus and drains into the IVC via the liver or via the ductus venosus.
The most oxygenated blood in the fetus is located in the…
umbilical vein.
A single umbilical artery is associated with..
congenital and chromosomal anomalies.
The umbilical arteries and veins are derived from…
allantois.
In the 3rd week, the yolk sac forms the…
allantois which extends into the urogenital sinus.
The allantois becomes the…
urachus, a duct between fetal bladder and yolk sac.
Failure of the urachus to obliterate results in (3):
- patent urachus 2. urachal cyst (partial failure) 3. vesicourachal diverticulum
A patent urachus allows…
urine discharge from the umbilicus.
A urachal cyst is a…
fluid-filled cavity lined with uroepithelium, between the umbilicus and bladder.
A urachal cyst can lead to…
infection and adenocarcinoma.
A veicourachal diverticulum is…
outpouching of the bladder.
The vitelline duct is…
a connection from the yolk sac to the midgut lumen. It is obliterated in the 7th week.
Failure of the vitelline duct to close results in (2):
- vitelline fistula 2. meckel diverticulum
Vitelline fistula causes…
meconium discharge from the umbilicus.
Meckel diverticulum has partial closure of the vitelline duct with the patent portion…
attached to the ileum (a true diverticulum).
A meckel diverticulum may contain…
ectopic gastric mucosa and/or pancreatic tissue leading to melena, periumbilical pain and ulcers.
The 1st aortic arch becomes…
part of the maxillary artery.
The 2nd aortic arch becomes…
the stapedial artery and hyoid artery.
The 3rd aortic arch becomes…
the common carotid artery and the proximal part of the internal carotid artery.
The 4th aortic arch becomes..
the aortic arch on the left and the right subclavian.
The 6th aortic arch becomes…
the proximal part of the pulmnoary arteries and the ductus arteriosus (on the left).
The branchial apparatus is composed of…
branchial clefts, arches and pouches.
The branchial clefts (grooves) are derived from…
ectoderm.
The branchial arches are derived from…
mesoderm (muslces, arteries) and neural crest (bone, cartilage).
The branchial pouches are derived from…
endoderm.
The 1st branchial cleft develops into the…
external auditory meatus.
the 2nd through 4th branchial clefts form…
temporay cervical sinuses which are obliterated by proliferation of 2nd arch mesenchyme.
A persistent cervical sinus leads to…
a branchial cleft syst within the lateral neck.
1st branchial arch cartilage derivatives
-meckel cartilage: mandible, malleus, incus, spheno-mandibular ligament
1st branchial arch muscle derivatives
-muscles of mastication (temporalis, masseter, lateral and medial pterygoids) -mylohyoid -anterior belly of digastric -tensor tympani -tensor veli palatini
1st branchial arch nerves
CN V2 and V3
Abnormality of the 1st branchial arch leads to…
Treacher Collins Syndrome (which is when the first arch neural crest fails to migrate leading to mandibular hypoplasia and facial abnormalities)
2nd branchial arch cartilage derivatives
Reichert cartilage (stapes, styloid process, lesser horn of the styoid and stylohyoid ligament)
2nd branchial arch muscle derivatives
Muscles of facial expression (stapedius, stylohyoid, platysma, belly of digastric)
2nd branchial arch nerve derivatives
CN VII (facial expression)
Abnormalities of the 2nd branchial arch leads to…
congenital pharyngocutaneous fistula (persistence of the cleft and pouch leads to a fistula between the tonsillar area and lateral neck)
3rd branchial arch cartilage derivatives
greater horn of hyoid
3rd branchial arch muscle derivatives
stylopharyngeus
3rd branchial arch nerve derivative
CN IX
4th-6th branchial arch cartilage derivatives
-thyroid -cricoid -arytenoids -corniculate -cuneiform
4th branchial arch nerve derivative
CN X (superior laryngeal branch)
6th branchial arch nerve derivative
CN X (recurrent laryngeal branch)
The 1st branchial pouch develops into…
the middle ear cavity, eustachian tube and mastoid air cells. (endoderm-lined ear structures)
The 2nd branchial pouch develops into…
epithelial lining of the palatine tonsil.
The 3rd branchial pouch develops into…
dorsal wings –> inferior parathyroids ventral wings –> thymus
The 4th branchial pouch develops into…
dorsal wings –> superior parathyroids
DiGeorge Syndrome is due to…
aberrant development of the 3rd and 4th branchial pouches which leads to T-cell deficiency (thymic hypoplasia) and hypocalcemia (failure of parathyroid devo).
MEN2A is due to a…
mutation of germline RET (neural crest cells).
Features of MEN2A (3)
-pheochromocytoma (adrenal medulla) -parathyroid tumor (3rd/4th pouches) -medullary thryoid cancer (4th/5th pouches)
Cleft lip is due to…
failure of fusion of the maxillary and medial nasal processes.
Cleft palate is due to..
failure of fusion fo the two lateral palatine processes or failure of fusion of lateral palatine processes with the nasal septum and/or median palatine process.
Default emryological development is…
female. The mesonephric duct degenerates and the paramesonephric duct develops.
The SRY gene is located on the…
Y chromosome and produces testis-determining factor which causes the testes to develop.
Sertoli cells secrete…
mullerian inhibitory factor (MIF) that suppresses the development of the paramesonephric ducts.
Leydig cells secrete…
androgens taht stimulate the development of the mesonephric ducts.
The parapmesonephric (mullerian) ducts develop into…
female internal structures (fallopian tubes, uterus, uppe portion of the vagina).
The lower portion of the vagina is from the…
UG sinus.
Mullerian duct abnormalities result in…
anatomical defects that may present as primary amenorrhea with fully developed secondary sex characteristics.
The mesonephric (wolffian) ducts develop into…
male internal structures (except prostate) - seminal vesicles, epididymis, ejaculatory duct and ductus deferens.
A bicornate uterus results from…
incomplete fusion of the paramesonephric ducts. Can lead to recurrent miscarriages.
Complete failure of fusion of the paramesonephric ducts leads to…
double uterus and vagina.
No sertoli cells or a lack of MIF will lead to…
development of both male and female internal genitalia and male external genitalia.
5-alpha reductase deficiency leads to…
inability to convert testosterone into DHT; pts will have male internal genitalia and ambiguous external genitalia until puberty (when increased testosterone levels cause masculinization).
In the female, the genital tubercle becomes…
the glans clitoris and vestibular bulbs.
In the male, the genital tubercle becomes…
the glans penis and corpus cavernosum/spongiosum.
In the female, the urogenital sinus becomes…
the greater vestibular glands (Bartholin) and the urethral/paraurethral glands (Skene).
In the male, the urogenital sinus becomes…
the bulbourethral glands of Cowper and the prostate gland.
In the female, the urogenital folds become…
the labia minora.
In the male, the urogenital folds become…
the ventral shaft of the penis.
In the female, the labioscrotal swelling becomes the…
labia majora.
In the male, the labioscrotal swelling becomes the..
scrotum.
Hypospadias is an…
abnormal opening of the penile urethra on the inferior (ventral) side of the penis due to failure of the urethral folds to close.
Fix hypospadias to prevent..
UTIs.
Epispadias is…
an abnormal opening of the penile urethra on the superior (dorsal) side of the penis due to faulty positioning of the genital tubercle.
Epispadias is associated with…
exstrophy of the bladder.
The male remnant of the gubernaculum is…
anchoring the testes within the scrotum.
The female remnant of the gubernaculum is…
the ovarian ligament and the round ligament.
The male remnant of the processus vaginalis forms…
the tunica vaginalis.
The female remnant of the processus vaginalis is…
obliterated.
The left ovary/testis is drained via the…
left gonadal vein to the left renal vein to the IVC.
The right ovary/testis is drained via the..
right gonadal vein to the IVC.
Ovaries and testes lymph drain to the…
para-aortic LNs.
The distal vagina/vulva/uterus drain lymph to the…
superficial inguinal nodes.
The proximal vagina/uterus drains lymph to the…
obturator, external iliac and hypogastric nodes.
The left spermatic vein enters the left renal vein at a 90 degree angle leading to…
increased pressure compared to the right and more common varicoceles on the left.
The infundibulopelvic (suspensory) ligament connects…
the ovaries to the lateral pelvic wall.
The infundibulopelvic (suspensory) ligament contains…
the ovarian vessels. Need to be ligated during oophorectomy to avoid bleeding.
The ureter courses retroperitoneally close to…
the gonadal vessels and thus is at risk of injury during ligation of the ovarian vessels.
The cardinal ligament connects…
the cervix to the side wall of the pelvis.
The cardinal ligament contains…
the uterine vessels. The ureter is at risk during ligation of the uterine vessels in a hysterectomy.
The round ligament connects…
the uterine fundus to the labia majora.
The round ligament travels through…
the round inguinal canal above the artery of Sampson.
The broad ligament connects…
the uterus, fallopian tubes and ovaries to the pelvic side wall.
The broad ligament contains…
the ovaries, fallopian tubes and round ligaments.
The components of the broad ligament are the…
mesosalpinx, mesometrium and mesovarium.
The ovarian ligament connects the…
medial pole of the ovary to the lateral uterus.
Histology of the vagina
stratified squamous epithelium, nonkeratinized
Histology of the ectocervix
stratified squamous epithelium, nonkeratinized
Histology of the endocervix
simple columnar epithelium
Histology of the transformation zone
squamocolumnar juction (most common area for cervical cancer)
Histology of the uterus
simple columnar epithelium with long tubular glands
Histology of the fallopian tube
simple columnar epithelium, many ciliated cells, a few secretory (peg) cells
Histology of the ovary (outer surface)
simple cuboidal epithelium (germinal)
Female Sexual Response Cycle
- phase of excitement (uterus elevates, vaginal lubrication) 2. plateau (expansion of inner vagina) 3. orgasm (contraction of uterus) 4. resolution
Female sexual response cycle is mediated by the..
autonomic nervous system.
Pathway of sperm during ejaculation
Semniferous tubules - epididymis - vas deferens - ejaclatory ducts - urethra - penis
Erection is innervated by the…
PNS (pelvic nerve). NO leads to increased cGMP causes smooth muscle relaxation, vasodilation and it becomes erect.
When the pelvic nerve secretes NE, this leads to..
an increase in calcium leading to smooth muscle contraction, vasoconstriction and this is antierectile.
Emission is innervated by…
the SNS (hypogastric nerve).
Ejaculation is innervated by…
visceral and somatic nerves (pudendal).
Spermatogonia (germ cells) maintain the…
germ pool and produce primary spermatocytes. They line the semniferous tubules.
Sertoli cells secrete…
inhibin (inhibits FSH) and androgen-binding protein (maintains local testosterone) and MIF.
Tight junctions between adjacent sertoli cells form..
the blood-testis barrier which isolates gametes from autoimmune attack.
Sertoli cells also support…
developing spermatozoa and regulate spermatogenesis.
Sertoli cells are sensitive to…
temperature. Increased temp leads to decreased sperm and increased inhibin.
The sertoli cells line…
seminiferous tubules.
The sertoli cells convert…
androstenedione to estrogen via aromatase.
Increased temperature of the testes is seen in both…
varicocele and cryptorchidism.
The Leydig cells secrete..
testosterone in the presence of LH. (unaffected by temp)
Estrogen sources
Ovary (17beta-estradiol) Placenta (estriol) Adipose tissue (estrone via aromatization)
Potency of the estrogens
estradiol > estrone > estriol
Estrogen is necessary for development of…
genitalia and breast and female fat distribution.
Estrogen is needed for growth of…
the follicle, endometrial proliferation and increased myometrial excitability.
Estrogen upregulates…
estrogen, LH and progesterone receptors.
Estrogen has feedback inhibition of…
FSH and LH, then an LH surge. It also stimulates prolactin secretion.
Estrogen increases…
transport proteins and SHBG; it increases HDL and decreases LDL
Estrogen during pregnancy:
50-fold increase in estradiol and estrone 1000-fold increase in estriol (indicator of fetal well-being)
Estrogen receptors are expressed in the…
cytoplasm and then translocate to the nucleus when bound.
In the theca cells, LH stimulates…
desmolase to convert cholesterol into androstenedione (which travels to the granulosa cells.
In the granulosa cells, FSH stimulates…
aromatase to convert androstenedione into estrogens.
Sources of progesterone
-corpus luteum -placenta -adrenal cortex -testes
Progesterone stimulates…
endometrial glandular secretions and spiral artery development.
Progesterone maintains…
pregnancy.
Progesterone decreases….
myometrial excitability (causes uterine smooth muscle relaxation) and estrogen receptor expressivity.
Progesterone produces…
thick cervical mucus, which inhibits early sperm entry into the uterus.
Progesterone increases…
temperature.
Progesterone inhibits…
LH and FSH.
Progesterone prevents…
endometrial hyperplasia.
The fall in progesterone after delivery acts to…
disinhibit prolactin which leads to prolactin.
Tanner Stages
I = childhood II = pubic hair appears (pubarche); breast buds (thelarche) III = pubic hair darkens, becomes curly; penis size/length increases; breasts enlarge IV = penis width increases; darker scrotal skin; development of glans; raised areolae V = adult; areolae no longer raised
The phase of the menstrual cycle that can vary in length is the…
follicular phase; luteal phase is usually a constant 14 days. Ovulation day + 14 days = menstruation
Decreased progesterone leads to…
decreased fertility.
Oligomenorrhea
> 35 day cycle
Polymenorrhea
Metrorrhagia
frequent but irregular bleeding (intermenstrual)
Menorrhagia
> 80 mL blood loss or > 7 days of menses (heavy menstrual bleeding)
Menometrorrhagia
heavy, irregular menstruation at irregular levels
Increased estrogen midcycle leads to…
the LH surge leads to ovulation leads to progesterone release from the corpus luteum. Then, progesterone levels fall (if no implantation) leading to menstruation via apoptosis of endometrial cells.
Primary oocytes begin…
meiosis I during fetal life and complete meiosis I just prior to ovulation.
Meiosis I is arrested in…
prophase I for years until ovulation (primary oocytes).
Meiosis II is arrested in…
metaphase II until fertilization (secondary oocytes).
If fertilizaiton does not occur within 1 day, then the…
secondary oocyte degenerates.
Ovulation is caused when…
increased estrogen and increased GnRH receptors on the anterior pituitary cause LH release leading to ovulation (rupture of the follicle).
Temperature during ovulation is…
increased from progesterone.
Mittelschmerz refers to…
transient mid-cycle ovulatory pain; classically associated with peritoneal irritation (follicular swelling, fallopian tube contraction). This can mimic appendicitis.
Fertilization most commonly occurs in the…
upper end of the fallopian tube (the ampulla). It occurs within one day of ovulation.
Implantation within the wall of the uterus occurs…
6 days after fertilization.
Syncytiotrophoblasts secrete…
hCG, which is detectable in the blood 1 week after conception and on the home urine test 2 wks after conception.
Suckling is required to maintain…
milk production since increased nerve stimulation increases oxytocin and prolactin.
Prolactin induces and maintains…
lactation and decreases reproductive fxn (decreases LH/FSH).
Oxytocin assists in…
milk letdown and promotes uterine contractions.
Breastmilk contains…
maternal Igs, macrophages and lymphocyts.
Breastmilk decreases risk for the child to develop….
asthma, allergies, DM and obesity (and infxns).
Exclusively breastfed infants require….
vitamin D supplementation.
Breastfeeding decreases maternal risk of…
breast and ovarian cancer.
hCG maintains…
the corpus luteum (and thus progesterone) for the 1st trimester by acting like LH to stimulate luteal cells.
In the 2nd and 3rd trimesters, the placenta synthesizes…
its own estriol and progesterone and the corpus luteum degenerates.
The alpha subunit of hCG is structurally….
identical to alpha subunits of LH, FSH, and TSH. The beta subunit is unique.
hCG is greatly increased in…
multiple gestations, hydatiform moles, and choriocarcinoma.
During menopause, there is decreased…
estrogen production due to age-linked decline in the number of ovarian follicles.
The source of estrogen after menopause becomes…
peripheral conversion of androgens. The increase in androgens leads to hirsutism.
Test for menopause with…
greatly increased FSH (due to loss of negative feedback on FSH due to decreased estrogen).
Hormonal changes during menopause (4)
- decreased estrogen 2. increased FSH 3. increased LH 4. increased GnRH
Menopause causes:
HAVOCS -Hot flashes -Atrophy of the vagina -Osteoporosis -Coronary artery disease -Sleep disturbances
Spermatogenesis begins at…
puberty with spermatogonia. Full development takes 2 months. It occurs in the seminiferous tubules.
Spermatogenesis produces…
spermatids that undergo spermiogenesis (loss of cytoplasmic contnets, gain of acrosomal cap) to form mature spermatozoon.
Sources of Androgens
DHT and testosterone (testis) Androstenedione (adrenal)
Potency of the androgens
DHT > testosterone > androstenedione
Functions of Testosterone (5)
- differentiation of epididymis, vas deferns, seminal vesicles 2. growth spurt 3. deepening voice 4. closing of epiphyseal plates (via estrogen conversion) 5. libido
Functions of DHT (2)
- differentiation of penis, scrotum, prostate (early) 2. prostate growth, balding, sebaceous gland activity (late)
Testosterone is converted to DHT by…
5alpha-reductase.
In the male, androgens are converted to estrogen by…
cytochrome P450 aromatase (mainly in adipose tissue and testis).
Exogenous testosterone leads to inhibition of…
the hypothalamic-pituitary-gonadal axis leading to decreased intratesticular testosterone leading to decreased testicular size and azoospermia.
Klinefelter Syndrome Features (7)
-XXY (male) -testicular atrophy -eunuchoid body shape -tall -gynecomastia -female hair distribution -presence of inactivated X chromoxome (barr body)
In Klinefelter, the dysgenesis of the seminiferous tubules leads to…
decreased inhibin and increased FSH.
Turner Syndrome Features (8)
-XO (female) -short stature -ovarian dysgenesis (streak ovary) -shield chest -bicuspid aortic valve -preductal coarctation -lymphatic defects (webbed neck, cystic hygroma) -horseshoe kidney
Signs of preductal coarctation
femoral
Double Y males features (XYY) (5)
-phenotypically normal -very tall -severe acne -antisocial behavior -normal fertility
True hermaphroditism features
-46 XX or 47 XXY -both ovary and testicular tissue present -ambigous genitalia
Increased T, Increased LH
defective andgrogen receptor
Increased T, Decreased LH
testosterone secreting tumor or exogenous steroids
Decreased T, Increased LH
primary hypogonadism
Decreased T, Decreased LH
hypogonadotropic hypogonadism
Female Pseudohermaphrodite (XX)
-ovaries are present but external genitalia are virilized or ambiguous -due to excessive exposure to androgenic steroids during early gestation (CAH or exogenous)
Male Pseduohermaphrodite (XY)
-testes present but external genitalia are female or ambiguous
Aromatase Deficiency Features (3)
-inability to synthetize estrogens from androgens -masculinization of female infants and increased androgens -can present with maternal virilization during pregnancy
Androgen Insensitivity Features (5)
-defect in androgen receptor resulting in normal looking female -uterus and fallopian tubes absent -scant sexual hair -testes often in labia majora (remove to prevent malignancy) -increased T, E, and LH
5alpha-reductase deficiency features (6)
-autosomal recessive -inability to convert testosterone to DHT -ambiguous genitalia until puberty -testosterone/estrogen levels normal -LH is normal/increased -internal genitalia normal
Kallmann syndrome features
-failure to complete pubery -defective migration of GnRH cells and formation of olfactory bulb -decreased synthesis of GnRH -anosmia -decreased GnRH, FSH, LH, testosterone -infertility
A hydatidiform mole is a…
cystic swelling of chorionic villi and proliferation of chorionic epithelium (only trophoblast).
Treatment for hydatidiform moles
dilation and curettage and methotrexate (have to monitor beta-hCG after)
Karyotype of hydatidiform moles
Complete: 46 XX; 46 XY Partial: 69 XXX; 69 XXY; 69 XYY
Uterine size in hydatidiform moles
Complete: increased
Conversion to choriocarcinoma in hydatidiform moles
Complete: 2% Partial: rare
Fetal parts in hydatidiform moles
Complete: none Partial: Yes
Components of the hydatidiform moles
Complete: nucleated egg + single sperm (duplicates paternal DNA) Partial: 2 sperm + 1 egg
Symptoms of hydatidiform moles
Complete: vaginal bleeding, enlarged uterus, hyperemesis, pre-eclampsia, hyperthyroidism Partial: vaginal bleeding, abdominal pain
Imaging of hydatidiform moles
Compete: honeycombed uterus or “clusters of grapes” or “snowstorm” on U/S Partial: fetal parts
Gestational hypertension is defined as…
BP > 140/90 after the 20th week.
Treat gestational HTN with…
antihypertensives (alpha-methyldopa, labetalol, hydralazine, nifedipine) and deliver at 39 weeks.
Preeclampsia is defined as…
HTN, proteinuria (>300 mg/24 hr) after the 20th wk of gestation.
End-organ damage from severe preeclampsia results in…
HA, scotoma, oliguria, increased AST/ALT, and thrombocytopenia.
Preeclampsia is caused by…
abnormal placental spiral arteries and results in maternal endothelial dysfunction, vasoconstriction or hyperreflexia.
The incidence of preeclampsia is increased in pts with…
preexisting HTN, diabetes, chronic renal dz or autoimmune disorders.
Complications of preeclampsia (5)
- placental abruption 2. coagulopathy 3. renal failure 4. uteroplacental insufficiency 5. eclampsia
Treatment of preeclampsia
-antihypertensives -deliver at 34 wks if severe -IV magnesium sulfate (to prevent seizure)
Eclampsia is…
preeclampsia + maternal seizures.
Maternal death in eclampsia is due to…
stroke leading to intracranial hemorrhage or ARDS.
Treatment of eclampsia is…
antihypertensives IV magnesium sulfate immediate delivery
HELLP Syndrome is…
Hemolysis, Elevated Liver enzymes, and Low Platelets (a manifestation of severe preeclampsia; deliver immediately)
Placental abruption is…
premature separation of the placenta from the uterine wall before delivery of the infant. Life threatening for both mother and fetus.
Risk factors for placental abruption include (5)…
trauma smoking HTN preeclampsia cocain abuse
Presentation of placental abruption
-abrupt, painful bleeding in 3rd trimester -possible DIC -maternal shock -fetal distress
Placental accreta, increta and percreta are due to…
defective decidual layers leading to abnormal attachment and separation after delivery.
Risk factors for placental accreta/increta/percreta include (3)…
prior C-section inflammation placenta previa
Placenta accreta
placenta attaches to the myometrium without penetrating it
Placenta increta
placenta penetrates into myometrium
Placenta percreta
placenta penetrates through the myometrium adn into the uterine serosa; can result in placental attachment to rectum or bladder
Presentation of Placenta accreta/increta/percreta
-no separation of placenta after delivery leading to massive bleeding
Placenta previa is…
attachment of the placenta to the lower uterine segment. It lies near, partially covers or completely covers the internal cervical os. (painless)
Risk factors for placenta previa (2)
multiparity prior C-section
Retained placental tissue may cause…
postpartum hemorrhage and increases risk of infection.
Ectopic pregnancy most often occurs in the…
ampulla of the fallopian tube.
Ectopic pregnancy should be suspected with a hx of…
amenorrhea, lower-than-expected rise in hCG and sudden lower abdominal pain. (+/- bleeding)
Ectopic pregnancy is confirmed with…
ultrasound.
Risk factors for ectopic pregnancy (4)
-hx of infertility -salpingitis -ruptured appendix -prior tubal surgery
Polyhdramnios (> 1.5-2 L) is associated with…
fetal malformations (inability to swallow amniotic fluid), maternal diabetes, and multiple gestations.
Oligohydramnios (
placental insufficiency, bilateral renal agenesis or posterior urethral valves (inability to excrete urine).
Profound Oligohydramnios can cause…
POTTER sequence.
Dysplasia/Carcinoma in situ is…
disordered epithelial growth that begins at the basal layer of squamocolumnar junction and extends outward.
Dysplasia/Carcinoma in situ is associated with….
HPV 16 and HPV 18 which both produce the E6 gene (inhibits p53) and E7 (inhibits Rb)
Dysplasia/Carcinoma in situ is typically…
asymptomatic or presents as abnormal vaginal bleeding. Can progress to invasive carcinoma (catch early with pap smear).
Risk factors for dysplasia/carcinoma in situ
-multiple sexual partners -smoking -early intercourse -HIV
Invasive carcinoma is often…
squamous cell carcinoma. Lateral invasion can block the ureters, causing renal failure.
Endometritis is…
inflammation of the endometrium (with plasma cells and lymphocytes).
Endometritis is associated with…
retained products of conception following delivery/miscarriage/abortion or foreign bodies such as an IUD.
Retained material in the uterus promotes…
infxn by bacterial flora from the vagina or intestinal tract.
Treatment for endometritis
gentamicin + clindamycin (+/- ampicillin)
Endometriosis is…
non-neoplastic endometrial glands/stroma outside of the endometrial cavity; most commonly in the ovaries, pelvis adn peritoneum; normal sized uterus.
In the ovary, endometriosis appears as…
an endometrioma (blood-filled “chocolate cyst”).
Endometriosis can be due to…
retrograde flow, metaplastic transformation of multipotent cells or transportation of endometrial tissue via the lymphatic system.
Endometriosis is characterized by…
cyclic pelvic pain, bleeding, dysmenorrhea, dyspareunia, dyschezia and infertily.
Treatment for Endometriosis
NSAIDs OCPs progestins GnRH agonists surgery
Adenomyosis is…
extension of the endometrial tissue (glandular) into the uterine myometrium caused by hyperplasia of the basalis layer of the endometrium.
Adenomyosis is characterized by….
dysmenorrha, menorrhagia and an enlarged, soft, globular uterus.
Treatment for Adenomyosis
hysterectomy
Adenomyoma (polyp) is a…
well-circumscribed collection of endometrial tissue within the uterine wall. May contain smooth muscle cells.
Endometrial hyperplasia is…
abnormal endometrial gland proliferation caused by excess estrogen stimulation. Give an increased risk for endometrial carcinoma.
Endometrial hyperplasia manifests as…
postmenopausal vaginal bleeding.
Risk factors for endometrial hyperplasia include…
anovulatory cycles, hormone replacement therapy, polycystic ovarian syndrome, and granulosa cell tumor.
Endometrial carcinoma clinically presents with…
vaginal bleeding at ages 55-65.
Risk factors for endometrial carcinoma include…
prolonged use of estrogen w/o progestins obesity diabetes HTN nulliparity late menopause (often preceded by endometrial hyperplasia)
Leiomyoma (aka fibroid) often presents with…
multiple discrete tumors. Increased incidence in black females from 20-40 yrs old. It is a benign smooth muscle tumor.
Leiomyomas are sensitive to…
estrogen so the tumor size increases with pregnancy and decreases with menopause.
Leiomyoma manifestations include…
asymptomatic, abnormal uterine bleeding, miscarriage. Severe bleeding may cause iron deficiency anemia.
Leiomyomas do not progress to…
leiomyosarcoma.
Histology of Leiomyoma
whorled pattern of smooth muscle bundles with well-demarcated borders
Polycystic Ovarian Syncrome (PCOS) is…
hyperandrogenism due to deranged steroid synthesis by theca cells and hyperinsulinemia.
PCOS results in…
enlarged, bilateral cystic ovaries. It presents with amenorrhea, hirsutism, acne and infertility. Associated with obesity.
PCOS has an increased risk for…
endometrial cancer secondary to increased estrogens from aromatization of testosterone and absence of progesterone.
Treatment for PCOS
-weight reduction -OCPs -antiandrogens -clomiphene citrate -metformin -cyclic progesterones
Lab features of PCOS
-increased LH and FSH (ratio is LH:FSH, 3:1) -increased testosterone -increased estrogen -increased insulin
PCOS is the most common cause of….
infertility in women.
Follicular cyst is a…
distention of unruptured graafian follicle. May be associated with hyperestrogenism and endometrial hyperplasia.
Corpus luteum cyst is…
a hemorrhage into persitent corpus luteum.
Theca-lutein cyst
-often bilateral/multiple -due to gonadotropin stimulation -associated with choriocarcinoma and moles
Hemorrhagic cyst
-blood vessel rupture in cyst wall -cyst grows with increased blood retention
Dermoid cyst
-mature teratoma -cystic growths filled with various types of tissue such as fat, hair, teeth, etc.
Endometrioid cyst
-endometriosis within ovary with cyst formation -varies with menstural cycle -when filled with dark, reddish-brown blood, called a “chocolate cyst”
Risk of ovarian neoplasm is increased with…
age, infertility, endometriosis, PCOS, genetics (BRCA-1/2, HNPCC, fam hx).
Risk of ovarian neoplasm decreases with…
previous pregnancy, hx of breastfeeding, OCPs, tubal ligation.
Ovarian neoplasms presetn with…
adnexal mass, abdominal distention, bowel obstruction and pleural effusion.
Ovarian neoplasms can be monitored by measureing…
CA-125 levels (not for screening).
Serous cystadenoma features (3)
-thin-walled, uni or multi locular -lined with fallopian-like epithelium -often bilateral
Mucinous cystadenoma (2)
-multiloculated, large -lined by mucus-secreting epithelium
Endometrioma (3)
-mass arising from gorwth of ectopic endometrial tissue -complex mass on U/S -presents with pelvic pain, dysmenorrhea and dyspareunia
Mature cystic teratoma (dermoid cyst) (4)
-germ cell tumor (common in women 20-30) -contains elements form all 3 germ layers -presents with pain seoncdary to ovarian enlargement or torsion -can contain functional thyroid tissue and present as hyperthyroidism (struma ovarii)
Brenner tumor (2)
-solid tumor that is pale yellow-tan and appears encapsulated (looks like bladder) -coffee bean nuclei
Fibromas (3)
-bundles of spindle-shaped fibroblasts -Meigs syndrome -pulling sensation in groin
Meigs syndrome is a…
triad of fibroma, ascites and hydrothorax.
Thecoma (2)
-like granulosa cell tumors, may produce estrogen -usually present as abnormal uterine bleeding in a postmenopausal woman
Immature teratomas (3)
-aggressive -contains fetal (embryonic-like) tissue -neuroectoderm
Granulosa cell tumor (4)
-often produce estrogen and/or progesterone -present with abnormal uterine bleeding, xexual precocity, breast tenderness -usually in women in 50s -Call-Exner bodies (resemble primordial follicles)
Serous cystadenocarcinoma (2)
-frequently bilateral -psammoma bodies
Mucinous cystadenoma (2)
-pseudomyxoma pertonei (intraperitoneal accumulatio nof mucinous material from ovarian or appendiceal tumor)
Dysgerminoma (3)
-common in adolescents -sheets of uniform “fried egg” cells -tumor markers are hCG and LDH
Choriocarcinoma (7)
-develops during/after pregnancy in mother or baby -malignancy of trophoblastic tissue -no chorionic villi -increased frequency of theca-lutein cysts -presents with abnormal beta-hCG, SOB and hemoptysis -hematogenous spread to lungs -responds to chemo
Yolk sac (endodermal sinus) tumor (5)
-aggressive -in ovaries or testes and sacrococcygeal area in young children -yello, friable, solid mass -Schiller-Duval bodies (resemble glomeruli) -AFP tumor marker
Krukenberg tumor (2)
-GI malignancy that metastasizes to the ovaries -causes a mucin-secreting, signet cell adenocarcinoma
Vaginal Squamous Cell Carcinoma is usually…
secondary to cervical SCC.
Vaginal clear cell adenocarcionma affects…
women who had exposure to DES in utero.
Sarcoma botryoides affects…
girls
Fibroadenoma is a…
small, mobile firm mass with sharp edges most common in those younger than 35.
Fibroadenoma increases in size and tenderness with…
estrogen. It is not a precursor to cancer.
Intraductal papilloma is a…
small tumor that grows in the lactiferous ducts. Typically beneath the areola.
Intraductal papilloma presents with…
serous or bloody nipple discharge. Slight increased risk for carcinoma.
Phyllodes tumor is a…
large bulky mass of CT and cysts. “leaf-like” projections. (common in 6th decade)
Malignant breast tumors are commonly…
postmenopausal and arise from terminal duct lobular unit.
In malignant breast tumors, overexpression of…
estrogen/progesterone receptors or c-erbB2 is common.
Breast tumors are more aggressive if they are…
triple negative (ER -, PR -, Her2/Neu -).
The single most important prognostic factor for malignant breast cancer is…
axillary LN involvement indicating metastasis.
Most common location of malignant breast cancer
upper outer quadrant
Risk factors for malignant breast cancer (6)
- increased estrogen 2. increased total number of menstrual cycles 3. older age at 1st live birth 4. obesity 5. BRCA1 and BRCA2 mutations 6. African Amerian ethnicity
Ductal carcinoma in situ fills…
the ductal lumena and arises from ductal atypia. Seen as microcalcifications.
Ductal carcinoma in situ is an early malignancy…
without basement membrane penetration.
Comedocarcinoma is a subtype of…
DCIS. It is ductal and has caseous necrosis.
Paget Disease results from…
underly DCIS.
Paget Disease presents with…
eczematous patches on the nipple. It has Paget cells (large cells in dermis with clear halo.
Invasive ductal carcinoma is a…
firm, fibrous, rock-hard mass with sharp margins and small, glandular, duct-like cells. Gross stellate infiltration.
Invasive lobular carcinoma is often…
bilateral with multiple lesions in the same location; orderly row of cells (indian file).
Medullary breast carcinoma is a…
fleshy, cellular lymphocytic infiltrate.
Inflammatory breast carcinoma is a…
dermal lymphatic invasion. Presents with peau d’orange.
Proliferative breast disease presents with…
premsentrual breast pain, bilateral, multiple lesions, and fluctuation in mass size.
Histologic types of Proliferative breast disease
- Fibrosis 2. Cystic 3. Sclerosing adenosis 4. Epithelial hyperplasia
Fibrosis (proliferative brease disease)
hyperplasia of breast stroma
Cystic (proliferative breast disease)
fluid, billed, blue dome, ductal dilation
Sclerosing adenosis
increased acini and intralobular fibrosis; associated with calcifications; increased risk of cancer
Epithelial hyperplasia
increase in number of epithelial cell layers in terminal duct lobule; increased risk of carcinoma; occurs in women > 30
Acute mastitis is a…
breast abcess caused by cracks in the nipple from breast-feeding that leads to infxn from S. aureus
Acute mastitis should be treated with…
dicloxacillin and continued breast feeding.
Fat necrosis is a…
benign, usually painless lump that forms as a result of injury to breast tissue.
Fat necrosis findings
-calcifications on mammography -biopsy shows necrotic fat, giant cells
Gynecomastia results from…
hyperestrogenism (cirrhosis, testicular tumor, puberty, old age), Klinefelter syndrome and drugs.
Drugs that cause gynecomastia
-Spironolactone -marijuana -Digitalis -Estrogen -Cimetidine -Alcohol -Heroin -Dopaine D2 antagonists -Ketoconazole
Prostatitis usually presents with…
dysuria, frequency, urgency and low back pain.
Acute prostatitis is usually due to…
E. coli.
Benign prostatic hyperplasia (BPH) is characterized by…
smooth, elastic, firm nodular enlargement of the peiurethral lobes which compress the urethra into a vertical slit.
BPH often presesnts with…
increased frequency of urination, nocturia, difficulty stopping and starting stream, dysuria. Increased PSA
BPH may lead to…
distention/hypertrophy of the bladder, hydronephrosis, and UTIs.
Treatments for BPH
-alpha1 antagonists (terazosin, tamulosin which cause relaxation of smooth muscle) -finasteride
Prostatic adenocarcinoma arises most often from the…
posterior lobe (peripheral zone) of the prostate and is diagnosed by increased PSA and needle core biopsies.
Tumor markers of prostatic adenocarcinoma include…
PSA and PAP.
Prostatic adenocarcinoma may develop into…
osteoblastic metastases in the bone indicated by lower back pain and increased serum ALP.
Cryptorchidism is…
undescended testis, with impaired spermatiogenesis. Can have normal testosterone levels (Leydig cells unaffected by heat).
Cryptorchidism is associated with…
increased risk of germ cell tumors. Prematurity increases the risk.
Lab features of cryptorchidism
-decreased inhibin -increased FSH -increased LH -testosterone decreased in bilateral
Varicocele is…
dialted veins in the pampiniform plexus as a result of increased venous pressure. Most common cause of scrotal enlargment in adults.
Varicocele is most often on the…
left side because of increased resistance to flow from left gonadal vein drainage into the renal vein.
Varicocele appears as…
a “bag of worms” and is diagnosed by U/S w/ doppler.
Treatment for varicocele
varicocelectomy embolization
Risk factors for testicular germ cell tumors
-cryptorchidism -Klinefelter -young age
Seminoma features (5)
-painless, testicular enlargmeent -3rd decade -large cells in lobules with watery cytoplasm and a “fried egg” appearance -increased placental AFP -radiosensitive
Yolk sac tumor (testicular) (3)
-yellow, mucinous -schiller-duval bodies -common in boys
Choriocarcinoma (4)
-increased hCG -disordered syncytiotrophoblastic and cytotrophoblastic elements -hematogenous metastases to lungs and brain -may produce gynecomastia or hyperthyroid symptoms (hCG is an LH and TSH analog)
Teratoma (2)
-malignant in males (NOT in females) -increased hCG and/or AFP
Embryonal carcionma
-hemorrhagic mass with necrosis -painful -often glandular/papillary -increased hCG and normal AFP when pure
Leydig cell tumor (4)
-contains Reinke crystals -usually androgen producing -gynecomastia or precocious puberty -golden brown color
Sertoli cell tumor
-androblastoma from sex cord stroma
Testicular lymphoma
-arises from lymphoma metastases to testes
Tunica vaginals lesions are…
in the serous covering of the testis present as testicular masses that can be transilluminated.
Hydrocele
increaed fluid secondary to incomplete obliteration of processus vaginalis
Spermatocele
dialted epididymal duct
Penile SCC is most common in…
Asia, Africa and South America.
Precursor lesions to penile SCC
-Bowen disease -erythroplasia of Queyrat -bowenoid papulosis
Bowen Disease is in the…
penile shaft and presents as leukoplakia.
Erythroplasia of Queyrat is…
cancer of the glans that presents as erythroplakia.
Bowenoid papulosis presents as…
reddish papules.
Penile SCC is associated with…
HPV and a lack of circumcision.
Priapism is a…
painful, sustained erection.
Priapism is associated with…
trauma sickle cell disease (RBCs get trapped in vaculature) medications (anticoagulants, PDE-5 inhibitors, antidepressants, alpha-blockers and cocaine)
Leuprolide mechanism
-GnRH analog with agonist properties when used in a pulsatile fashion; antagonist properties when used continuously (downregulates GnRH receptor in the pituitary leading to decreased FSH/LH)
Clinical use of Leuprolide
infertility prostate cancer uterine fibroids precocious puberty
Clinical use of estrogens (ethinyl estradiol, DES, mestranol)
-hypogonadism or ovarian failure -mesntrual abnormalities -HRT in postmenopausal women -used in men with androgen dependent prostate cancer
Toxicity of estrogens
-increased risk of endometrial cancer -bleeding -clear cell adenocarcionma of vagina (DES) -increased risk of thrombi
Estrogens are contraindicated in…
ER + breast cancer and those with a hx of DVTs
Selective Estrogen Receptor Modulators (SERMs)
-Clomiphene -Tamoxifen -Raloxifene
Clomiphene is an…
antagonist at estrogen receptors in the hypothalamus that prevents normal feedback inhibition leading to increaed release of LH and FSH from the pituitary which stimulates ovulation.
CLompihene is used to treat…
infertility due to anovulation (PCOS).
Clomiphene may cause…
hot flashes, ovarian enlargement, multiple simultaneous pregnancies and visual disturbances.
Tamoxifen is an…
antagonist on breat tissue and agonist in bone and the uterus.
Tamoxifen is associated with…
endometrial cancer and thromboembolic events.
Tamoxifen is primarily used to treat and prevent recurrence of…
ER + breast cancer.
Raloxifene is an…
agonist on bone and antagonist at the uterus.
Raloxifene increases risk of…
thromboemblic events.
Raloxifene is used to treat…
osteoporosis bc it decreases resorption of bone.
HRT is used for…
relief of menopausal symptoms and osteoporosis.
Unopposed estrogen replacement therapy increases risk of…
endometrial cancer so progesterone is added.
Anastrozole/Exemestane are…
aromatase inhibitors used in postmenopausal women with breast cancer
Progestins MOA
bind progesterone receptors to decrease growth and increase vascularization of the endometrium
Progestins Use
used in oral contraceptives and in treatment of endometrial cancer and abnormal uterine bleeding
Mifepristone MOA
competitive inhibitor of progestins
Clinical use of mifepristone
termination of pregnancy (administered with misoprostol (PGE1))
In OCPs, estrogen and progestins inhibit…
LH/FSH and thus prevent the estrogen surge. No estrogen surge means no LH sruge means no ovulation.
In OCPs, progestins cause…
thickening of the cervical mucus (limiting access to sperm) and they inhibit endometrial proliferation making it less suitable for implantation.
Contraindications for OCPs
smokers > 35 hx of thromboembolism, stroke or estrogen-dependent tumors
Terbutaline is a…
beta2-agonist that relaxes the uterus; usted to decrease contraction frequency in women during labor.
Danazol MOA
synthetic androgen that acts as a partial agonist
Use of Danazol
endometriosis and angioedema
Toxicity of Danazol
-weight gain -edema -acne -hirsutism -masculinization -decreased HDL -hepatotoxicity
MOA of Testosterone and Methyltestosterone
agonist at androgen receptors
Use of Testosterone and Mehtyltestosterone
-hypogonadism -promotes development of secondary sex characteristics -stimulation of anabolism to promote recovery after burn or injury
Toxicity of testosterone
-masculinization -decrease intratesticular testosterone (gonadal atrophy due to decreased LH) -premature closure of epiphyseal plates -increased LDL, decreased HDL
Finasteride is a…
5alpha-reductase inhibitor that decreases the conversion of testosterone to DHT
Finasteride uses
-BPH -male pattern baldness
Flutamide is a…
nonsteroidal competitive inhibitor of androgens at teh testoterone receptor.
Flutamide is used in…
prostate carcinoma.
Ketoconazole inhibits…
steroid synthesis (inhibits 17,20-desmolase).
Spironolactone inhibits…
steroid binding, 17alpha-hydroxylase and 17,20-desmolase.
Ketoconazole and spironolactone are used in the treatment of…
PCOS to prevent hirsutism. Both have side effects of gynecomastia and amenorrhea.
Tamsulosin is an…
alpha1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for alpha1A,D receptor found on prostate.
Sildenafil and Vardenafil MOA
inhibit phosphodiesterase-5 causing increased cGMP, smooth muscle relaxation, increased blood flow and penile erection
Toxicity of Sildenafil and Vardenafil
-dyspepsia -impaired blue-green color vision -risk of life-threatening hypotension in pts taking nitrates (since they block teh breakdown of NO)
