558 terms

USMLE: Reproduction

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gene for embryogenesis: where is sonic hedgehog Shh gene expressed
produced at limb base in zone of polarizing activity
(hds: neural tube & notochord)
gene for embryogenesis: sonic hedgehog Shh gene is needed for (2); mutation causes
1. forming anterior-posterior axis
2. CNS development
mutation causes holoprosencephaly
gene for embryogenesis: where is Wnt-7 gene expressed?
apical ectodermal ridge (thickened ecotderm at distal end of each developing limb)
(hds: dorsal neural tube)
gene for embryogenesis: Wnt-7 gene is needed for
forming dorsal-ventral axis
gene for embryogenesis: hemeobox (HOX) gene is needed for (2). mutation causes
1. segmental organization of embryo in craniocaudal direction
2. code for transcription factors for limb growth
mutations cause appendages in wrong locations
(hds: hox activates TBX; TBX activates FGF to begin limb development)
gene for embryogenesis: where is FGF gene expressed
apical ectodermal ridge
gene for embryogenesis: FGF gene is needed for
fibroblast growth factor - limb lengthening
- stimulate mitosis of underlying mesoderm
early fetal development:
day 0
fertilization by sperm-->zygote
embyogenesis begins
early fetal development: week 1
when will hCG be detectable
hCG detectable 8 days after bloastocysts implantation
("sticks at day 6")
early fetal development:
within week 2
bilaminar disc (epiblast, hypoblast)
(2 weeks = 2 layers)
early fetal development:
within week 3
timlaminar disc (3 weeks = 3 layers)
gastrulation
primitive streak, notochord, mesoderm and it organization begin to form
early fetal development:
weeks 3-8
(embryonic period)
neural tube formed by neuroectoderm; closes by week 4
organogenesis
extremely susceptible to teratogens
early fetal development:
week 4
heart begins to beat
upper and lower limb buds begin to form
neural tube closes
(4 weeks = 4 limbs)
early fetal development:
week 6
fetal cardiac activity visible by transvaginal ultrasound
early fetal development:
week 10
genitalia have male/female characteristics
gastrulation
process that forms trilaminar disc
ecto-, meso-, endoderm established
starts w/ epiblast invaginating to form primitive streak
**
**
ectoderm derivatives:
surface ectoderm
epidermis
adenohypophysis (from Rathke pouch)
lens of eye
epithelial lining of mouth, sensory organs of ear, olfactory epithelium
anal canal below pectinate line
parotid, sweat, mammary glands
ectoderm derivatives: neuroectoderm
brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland)
retina and optic nerve
spinal cord
ectoderm derivatives:
neural crest
PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS)
melanocytes
chromaffin cells of adrenal medulla
parafollicular (C) cells of thyroid
pia and arachnoid
bones of skull
odontoblasts
aorticopulmonary septum
mesoderm derivatives
muscle
bone
CT
serous linings of body cavities (e.g. peritoneum)
spleen (from foregut mesentery)
cardiovascular structures
lumphatics
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 (bone and muscle)
endoderm derivatives
gut tube epithelium (including anal canal above pectinate line)
most of urethra (from genitourinary sinus)
luminal epithelial derivatives (e.g. lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)
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 embryonic period
disruption
secondary breakdown of previously normal tissue or structure (e.g. amniotic band syndrome)
malformation
intrinsic disruption
occurs during embryonic period (weeks 3-8)
sequence
abnormalities result from a single primary embryologic event (e.g. oligohydramnios--->Potter sequence)
Teratogen effect starting week 3 & week 8
week 3 - 8: "all-or-none" effects
week 8: growth & function issue
20 Teratogens (11 rx, 3 toxin, 5 other)
Rx
1. ACE inhibitors
2. Aminoglycosides
3. Anti-SZ rx
4. (uw) chloramphenicol
5. Diethylstilbestrol
6. folate blocker
7. isotretinoin
8. lithium
9. methimazole
10. Tetracycline
11. Thialidomide
12. Warfarin
Substance Abuse
13. EtOH
14. Cocaine
15. smoking
Other
16. iodine (too much or little)
17. maternal DM
18. methylmercury
19. vitamin A excess
20. X-ray
teratogens:
ACE inhibitors
renal damage
teratogens:
alkylating agents
absence of digits
multiple anomalies
teratogens: what does aminoglycosides cause
ototoxicity (CN8)
(mnemonic: A mean guy hit the baby in the ear)
teratogen: (uw) what is chloramphenicol associated w/?
gray baby syndrome
teratogens:
carbamaxepine
facial dysmorphism
developmental delay
neural tube defects
phalanx/fingernail hypoplasia
teratogens:
diethylstilbestrol (DES)
vaginal clear cell adenocarcinoma
congenital Mullerian anomalies
teratogens: (uw) what are 3 folate blockers? what do they cause (2)? what is an associated illness
1. Trimethoprim
2. sulfamethoxazole
3. anti-SZ rx
neural tube defects & anacephaly; leading to polyhydraminos
teratogens:
phenytoin
fetal hydantoin syndrome (cleft palate, cardiac defects, phalanx/fingernail hypoplasia)
teratogens: what is isotretinoin indication? what does it cause & what is needed during tx?
acne tx but cause multiple severe birth defects
contraception mandatory + ongoing pregnancy test
(mnemonic: isoTREATinoin)
teratogens: lithium is a tx for what? what heart condition does it cause?
treat bipolar
Ebstein anomaly (atrialized right ventricle)
teratogens:
methimazole
aplasia cutis congentia
teratogens: what is tetracylines indication? what does it cause in infant?
1st line antibiotic
discolored teeth
(mnemonic: TEETHracycline)
teratogens:
thalidomide
limb defects (phocomelia, micromelia - "flipper" limbs)
teratogens:
valproate
inhibition of maternal folate absorption--->neural tube defects
teratogens:
warfarin
bone deformities
fetal hemorrhage
abortion
ophthalmologic abnormalities
teratogens:
alcohol
common cause of birth defects and intellectual diability
fetal alcohol syndrome
teratogens:
cocaine
abnormal fetal growth and fetal addiction
placental abruption
teratogens:
smoking (nicotine, CO)
low birth weight (leading cause in developed countries)
preterm labor
placental problems
IUGR
ADHD
(nicotime-->vasoconstriction; CO-->impaired O2 delivery)
teratogens:
iodine (lack or excess)
congenital goiter or hypothyroidism (cretinism)
(uw) teratogens: maternal diabetes (3+3+3 uw)
embryopathy
1. caudal regression syndrome (anal atresia to sirenomelia)
2. heart defects
3. neural tube defect
placental vasculopathy
4. asphyxia
5. growth issue
6. polycythemia
(uw) increased fetal insulin
7. macrosomia: high insulin increases growth
8. hypertrophic heart
9. transient hypoglycemia after delivery (normalize after insulin remits)
teratogens:
vit A (excess)
very high risk for spontaneous abortion and birth defects (cleft palate, cardiac)
teratogens:
x-rays
microcephaly, intellectual disability
minimize by using lead shield
fetal alcohol syndrome
inc incidence of congenital anomalies:
pre- and postnatal developmental retardation
microcephaly
facial abnormalities (e.g. smooth philthrum, hypertelorism)
limb dislocation
heart defects
heart-lung fistulas and holoprosencephaly in most severe
leading cause of intellectual disability in US
fetal alcohol syndrome
mechanism of fetal alcohol syndrome
failure of cell migration
dizygotic twins: 1 or 2 amniotic sacs? placentas (chorions)?
2 amnion, 2 chorion
upon what does the degree of separation between monozygotic twins depend?
when the zygote split into 2
day 0: 2 amnion, 2 chorion (25%)
day 4: 2 amnion, 1 chorion (75%)
day 8 & after (rare): 1 aminon, 1 chorion
what happens to monozygotic twins that split after 13ds?
1 amnion 1 chorion
conjoined twins (embryonic disc formed before cleavage occurred)
**
**
fetal components of placental (2)
cytotrophoblast
syncytioytophoblast
what is cytotrophoblast
inner layer of chorionic villi of fetal component of placenta
what is syncytioytophoblast? what is unique about its surface receptor?
outer layer of chorionic villi of fetal component of placenta
lacks MHC-1 expression; evade maternal immune system
what does the syncytiotrophoblast secret? what is its function?
secret hCG
1. structurally similar to LH
2. stimulates corpus luteum to secrete progesterone during first trimester
what is the maternal component of placenta? what does it derive from?
decidua basalis
derived from endometrium
maternal blood in lacunae
structures within the umbilical cord (4)
2 umbilical arteries
1 umbilical vein
allantoic duct
Wharton jelly
umbilical arteries function
return deoxygenated blood from fetal internal iliac arteries to placenta
umbilical vein function
supplies oxygenated blood from placenta to fetus
drains into IVC via liver or ductus venosus
the presence of only 1 umbilical artery in the umbilical cord is associated with___
congenital and chromosomal anomalies
from what are the umbilical arteries and vein derived?
allantois
urachus
duct between fetal bladder and yolk sac
what the allantois becomes
in the 3rd week the yolk sac forms the ___, which extends into the ____ sinus
allantois
urogenital
patent urachus
total failure of urachus to obliterate--->urine discharge from umbilicus
urachal cyst
partial failure of urachus to obliterate
fluid-filled cavity lined w/ uroepithelium, between umbilicus and bladder
urachal cyst can lead to what?
infection
adenocarcinoma
vesicourachal diverticulum
slight failure of urachus to obliterate--->outpouching of bladder
vitelline duct
connects yolk sac to midgut lumen
7th week - obliterates (omphalo-mesenteric duct)
vitelline fistula
vitelline duct fails to close--->meconium discharge from umbilicus
Meckel diverticulum
partial closure of vitelline duct, w/ patent portion attached to ileum (true diverticulum)
may have heterotopic gastric and/or pancreatic tissue--->melena, hematochezia, abdominal pain
aortic arch derivatives develop into ___
arterial system
aortic arch derivatives:
1st
first part of maxillary artery (branch of external carotid)
aortic arch derivatives
figure
aortic arch derivatives:
2nd
stapedial artery
hyoid artery
aortic arch derivatives:
3rd
common carotid artery
proximal part of internal carotid artery
aortic arch derivatives:
4th
on left: aortic arch
on right: proximal part of right subclavian artery
aortic arch derivatives:
6th
proximal part of pulmonary arteries
on left only: ductus arteriosus
what does the ductus arteriosus become shortly after birth?
ligamentum arteriosum
what nerve gets caught by the ductus arteriosus?
left recurrent laryngeal nerve
branchial apparatus
aka
pharyngeal apparatus
branchial apparatus
composed of...
clefts
arches
pouches
branchial clefts are derived from...
ectoderm
branchial clefts are also known as...
branchial grooves
branchial arches are derived from...
mesoderm (muscles, arteries)
neural crest (bones, cartilage)
branchial pouches are derived from...
ectoderm
branchial cleft derivatives:
1st
external auditory meatus
branchial cleft derivatives:
2nd, 3rd, 4th
temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme
persistent cervical sinus--->branchial cleft cyst within lateral neck
CNs with both sensory and motor functions?
from what are they all derived?
V3, VII, IX, X
branchial arches
branchial arch derivatives: 1st
cartilage
Meckel cartilage:
mandible
malleus
incus
sphenomandibular ligament
branchial arch derivatives: 1st
muscles
temporalis, masseter, lateral/medial pterygoids (mastication)
mylohyoid
anterior belly of digastric
tensor tympani
tensor veli palatini
branchial arch derivatives: 1st
nerves
CN V2 and V3
branchial arch derivatives: 1st
abnormalities
Treacher-Collins syndrome:
1st arch neural crest fails to migrate--->mandibular hypoplasia, facial abnormalities
branchial arch derivatives: 2nd
cartilage
Reichert cartilage:
stapes
styloid process
lesser horn of hyoid
stylohyoid ligament
branchial arch derivatives: 2nd
muscles
muscles of facial expression
stapedius
stylohyoid
platysma
posterior belly of digastric
branchial arch derivatives: 2nd
nerves
CN VII (facial expression)
branchial arch derivatives: 2nd
abnormalities
congenital pharyngocutaneous fistula:
persistence of cleft and pouch-->fistula b/w tonsillar area and lateral neck
branchial arch derivatives: 3rd
cartilage
greater horn of hyoid
branchial arch derivatives: 3rd
muscles
stylopharyngeus
branchial arch derivatives: 3rd
nerves
CN IX
branchial arch derivatives: 4th-6th
cartilage
thyroid
cricoid
arytenoids
corniculate
cuneiform
branchial arch derivatives: 4th-6th
muscles (4th arch)
most pharyngeal constrictors
cricothyroid
levator veli palatini
branchial arch derivatives: 4th-6th
muscles (6th arch)
all intrinsic muscles of larynx except cricothyroid
branchial arch derivatives: 4th-6th
nerves
4th: CN X (superior laryngeal branch)
6th: CN X (inferior laryngeal branch)
branchial arch derivatives: 4th-6th
to what does arch 5 contribute?
nothing major
branchial arch derivatives:
which make up the posterior 1/3 of tongue?
3rd and 4th
branchial pouch derivatives: 1st
contributes to endoderm-lined structures of inner ear:
middle ear cavity
eustachian tube
mastoid air cells
branchial pouch derivatives: 2nd
epithelial lining of palatine tonsil
branchial pouch derivatives: 3rd
dorsal wings--->inferior parathyroids
ventral wings--->thymus
(both end up below 4th pouch structures)
branchial pouch derivatives: 4th
dorsal wings--->superior parathyroids
DiGeorge syndrome
aberrent development of 3rd and 4th branchial pouches--->T-cell deficiency (thymic aplasia), hypocalcemia (failure of parathyroid development)
DiGeorge syndrome is associated with...
cardiac defects (conotruncal anomalies)
MEN 2A
mutation of germline RET (neural crest cells)--->
pheochromocytoma (adrenal medulla)
parathyroud tumor: 3rd/4th pharyngeal pouch
medullary thyroid cancer (parafollicular cells): from neural crest cells; associated w/ 4th/5th pharyngeal pouches
cleft palate and cleft lip often have the same or different etiologies?
different
...but they often occur together
cleft lip
failure of fusion of maxillary and medial nasal processes (formation of primary palate)
cleft palate
failure of fusion of two lateral palatine processes or failure of fusion of lateral palatine processes w/ nasal septum and/or median palatine process
(formation of secondary palate)
genital embryology: sexually undifferentiated embryo has what genital ducts (2); what happens to them in female (XX)
female: default sex
1. mesonephric (Wolffian) duct degenerates
2. paramesonephric (Mullerian) duct develops
genital embryology: gene responsible for male genital development? what 2 cells does it work on?
SRY gene on chromosome Y produces testis-determining factor to influence:
1. Sertoli cells to make Mullerian inhibitory hormone (MIH): suppression of development of paramesonephric ducts
2. Leydig cells to make androgen that stimulate development of mesonephric ducts
(uw) genital embryology: 3 stages of gonad development
1. Gonadal: primordial germ cells from yolk sac move to genital ridge, forms primitive gonads; SRY gene starts influence
2. Ductal stage: male-paramesonephric duct regress (MIF), mesonephric duct develops; female - paramesonehpric duct develops
3. Genital: genital tubercle becomes glans penis or glans clitoris
genital embryology: mesonephric (Wolffian) duct
develops into male internal structures (except prostate): SEED:
seminal vesicles
epididymus
ejaculatory duct
ductus deferens
genital embryology: paramesonephric (Mullerian) duct
develops into female internal structures (fallopian tubes, uterus, upper portion of vagina)
genital embryology: what becomes the lower portion of the vagina?
urogenital sinus
genital embryology: Mullerian agenesis aka (2)? How does Mullerian agenesis present?
vaginal agenesis or MRKH syndrome
1. may present as primary amenorrhea (lack uterus & no upper vagina) in females
2. fully developed secondary female characteristics
3. functional ovaries
genital embryology: in females, the remnant of the mesonephric duct becomes:
Gartner duct
genital embryology: no Sertoli cells or lack of Mullerian inhibitory factor MIF leads to (2)
1. develop both male and female internal genitalia
2. male external genitalia
(uw) genital embryology: 5-alpha-reductase deficiency cause (2)
testosterone cannot convert to DHT
1. genetic defect in male infant, internal genitalia ok
2. external genitalia cannot develop properly, causing pseudo-hermaphroditism
(can be hypospadias to female external genital)
genital embryology: (uw) 3 hormones that influence sexual development
1. testosterone: male genitalia, spermatogenesis, male sexual development (muscle, libido)
2. dihydrotestosterone (DHT): external genitalia, prostate, hair growth
3. estrogen: endometrial proliferation, ovary granulosa cell, breast development
what causes septate uterus? how is it treated?
common anomaly
incomplete resorption of septum - decrease fertility
treat w/ septoplasty
female reproductive tract development involves lateral/vertical fusion & involution of what structure? what structure is it closely linked to & what is the significance?
paramesonephric duct
linked to mesonephric duct so uterine abnormalities is oft. associated w/ renal anomalies
incomplete fusion of the Mullerian duct cause what condition?
bicornuate uterus - inc risk of complicated pregnancy
total failure of fusion of the Mullerian duct cause what condition? uterus didelphys
uterus didelphys - double uterus, vagina, cervix; pregnancy possible
(uw) what imaging can differentiate bicornuate uterus w/ uterine septum? how are they different?
hysterosalpinogogram (HSG) w/ contrast: only show central filling defect
MRI can differentiate: septate uterus has normal outer contour; bicornuate uterus contour is abnormal
(HSG: Y shape - lower uterus segment w/ upper unfused horn; curly - fallopian tubes w/ contrast)
what 2 hormones influence the development of the genital swellings? what are the male & female analogs?
genital tubercle (2)
urogenital sinus (2)
urogenital folds
labioscrotal swelling
DHT or estrogen
genital tubercle
1. glans penis, glans clitoris
2. corps cavernosum + spongiosum, vestibular bulbs
urogenital sinus
1. bulbourethral glands, greater vestibular glands
2. prostate gland, urethral & paraurethral glands
urogenital folds
1. ventral penis shaft, labia minora
labioscrotal swelling
1. scrotum, labial majora
remnant of gubernaculum (band of fibrous tissue)
male: anchors testes within scrotum
female: ovarian & round ligament
male remnant of processus vaginalis (evagination of peritoneum)
male: forms tunica vaginalis
female: obliterated
gonadal venous drainage from left & right ovary/testes
left ovary/testis--->left gonadal vein--->IVC
(left takes longest way)
right ovary/testis--->right gonadal v.--->IVC
gonadal lymph drainage from
1. ovary or testes
2. distal vagina, vulva or scrotum
3. proximal vagina, uterus
1. ovaries/testes: para-aortic lymph nodes
2. distal vagina/vulva/scrotum: superficial inguinal nodes
3. prox vagina/uterus: obturator, external iliac, and hypogastric nodes
why is venous flow from left testis on male less laminar than on right? consequences?
left spermatic vein enters left renal vein at 90 degree angle
left venous pressure is higher - varicocele more common on left
infundibulopelvic ligament
aka
suspensory ligament of ovary
what does the suspensory ligament
connect? what does it contain?
ovaries to lateral pelvic wall
contains ovarian vessels
suspensory ligament should be ligated during what procedure
oophorectomy to avoid bleeding
where is the suspensory ligament? why is it dangerous?
retroperitoneal - close to gonadal vessels
risk of injury during ligation of ovarian vessels
cardinal ligament
connects
cervix to side wall of pelvis
cardinal ligament
structures contained
uterine vessels
cardinal ligament
what is at risk during ligation of uterine vessels during hysterectomy?
ureter
round ligament of the uterus
connects
uterine fundus to labia majora
round ligament of the uterus
derived from
gubernaculum
round ligament of the uterus
travels through what canal, above what artery?
round inguinal canal
artery of Sampson
broad ligament
connects
uterus, fallopian tubes, and ovaries to pelvic side wall
broad ligament
structures contained
ovaries
fallopian tubes
round ligaments of uterus
broad ligament
comprised of...
mesosalpinx
mesometrium
mesovarium
ovarian ligament
connects
medial pole of ovary to lateral uterus
ovarian ligament
derived from
gubernaculum
female reproductive epithelial histology:
vagina
stratified squamous
nonkeratinized
female reproductive epithelial histology:
ectocervix
stratified squamous
nonkeratinized
female reproductive epithelial histology:
transformation zone
squamocolumnar junction
(most common area for cervical cancer)
female reproductive epithelial histology:
endocervix
simple columnar
female reproductive epithelial histology:
uterus
simple columnar w/ long tubular glands in follicular phase, coiled glands in luteal phase
female reproductive epithelial histology:
fallopian tube
simple columnar, ciliated
female reproductive epithelial histology:
ovary, outer surface
simple cuboidal (germinal epithelium covering surface of ovary)
female sexual response cycle
1. excitement (uterus elevates, vaginal lubrication)
2. plateau (expansion of inner vagina)
3. orgasm (uterine contraction)
4. resolution
also: tachycardia, skin flushing
female sexual response cycle
mediated by
ANS
mnemonic for sperm pathway during ejaculation
SEVEN UP:
seminiferous tubules
epididymus
vas deferns
ejaculatory duct
(nothing)
urethra
penis
4 parts of male urethra
posterior
1. prostatic
2. membranous
anterior
3. bulbous
4. penile
typical injury to each part of the urethra:
1. membranous
2. bulbar
3. penile
1. membranous: pelvic fracture
2. bulbar: blunt force
3. penile: perineal straddle; penetrating injury
membranous or bulbar urethral injury cause urine to leak into what space
retropubic space
penile urethral injury cause urine to leak into what space
beneath deep fascia of Buck
if fascia is torn, urine escapes into superficial perineal space
erection is mediated by what nerve & what nervous system?
parasympathetic (pelvic nerve)
emission is mediated by what nerve & what nervous system?
sympathetic (hypogastric nerve)
ejaculation is mediated by what part of the nervous system?
visceral and somatic nerves (pedundal nerve)
how does parasympathetic stimulation via pelvic nerve stimulate an erection? inhibit it?
1. NO: increase cGMP causing smooth muscle relaxation, vasodilation, erection
2. NE: increase Ca2+ influx causing smooth muscle contraction, vasoconstriction, stop erection
spermatogonia (germ cells)
function
maintain germ pool
produce primary spermatocytes
spermatogonia (germ cells)
location
line seminiferous tubules
what is the feedback loop for FSH & LH in boys
FSH
1. stimulate sertoli cells makes inhibin
2. inhibin downregulate FSH
LH
1. stimulate testes to make testosterone
2. testosterone downregulate LH
what is the feedback loop for FSH & LH in girls
FSH
1. stimulate granulosa cell turns androgen to estrogen
2. estrogen stimulate follicle makes progesterone
LH
1. stimulate theca cell makes androgen
(uw) anorexia effect on GnRH loop
decrease fat cells & leptin
decrease GnRH
decrease FSH, LH, estrogen
Sertoli cells functions (5)
1. secrete inhibin > inhibit FSH
2. secrete androgen-binding protein-->maintain local testosterone levels
3. support, nourish developing spermatogonia
4. produce Mullerian inhibiting factor MIF
5. temperature-sensitive: dec sperm production and dec inhibit w/ inc temp
function of tight junctions between Sertoli cells
form blood-testis barrier--->isolate gametes from autoimmune attack
Sertoli cells
location
line seminiferous tubules
how do Sertoli cells maintain local testosterone levels?
convert testosterone and androstenedione to estrogen via aromatase
Sertoli cells are homologous to...
female granulosa cells
varicocele and cryptorchidism are associated with ___ temp (in regards to Sertoli cells)
inc
Leydig cells (endocrine cells)
function
secrete testosterone in presence of LH
testosterone production unaffected by temp
Leydig cells (endocrine cells)
location
interstitium
Leydig cells (endocrine cells) are homologous to...
female theca interna cells
estrogen
relative potency of forms
estradiol>estrone>estriol
estrogen
source
1. ovary (17-beta-estradiol)
2. placenta (estriol)
3. adipose tissue (estrone via aromatization)
estrogen
pulsatile GnRH--->FSH--(+)-->
aromatase: androgens--->estrogens
in granulosa cell
estrogen
pulsatile GnRH--->LH--(+)-->
desmolase: cholesterol---> androgrens (--->granulosa cell)
in theca interna cell
(uw) estrogen function (9)
1. development of genitalia and breast
2. female fat distribution
3. follicle growth, endometrial proliferation, inc myometrial excitability
4. inc transport proteins, SHBH
5. inc HDL, dec LDL
6. upregulate estrogen, LH, FSH, progesterone receptors
7. feedback inhibition of FSH, LH, then LH surge
8. stimulation of prolactin secretion
9. initially long bone growth (epiphyseal plate growth); then stunned growth by inducing plate closure
estrogen
where are receptors expressed?
cytoplasm
translate to nucleus when bound by estrogen
estrogen
levels in pregnancy
estrone and estradiol inc 50-fold
estriol inc 1000-fold (indicator of fetal well-being)
progesterone
source
corpus luteum
placenta
adrenal cortex
testes
progesterone levels post-delivery and why
fall after delivery--->disinhibits prolactin--->lactation
inc progesterone is indicative of __
ovulation
progesterone
function
1. stimulates endometrial glandular secretions and spiral artery development
2. maintenance of pregnancy
3. dec myometrial excitability
4. thick cervical mucus production (sperm block)
5. inc body temp
6. inhibition of gonadotropins (FSH, LH)
7. uterine SM relaxation (prevent contractions)
8. dec estrogen receptor expression
9. prevents endometrial hyperplasia
what are the 3 components and how are they assign
independently assigned
1. genitalia
2. pubic hair
3. breast
(pt can have stage 1 genitalia & 2 breast)
Tanner stages of sexual development 1
childhood (prepubertal)
Tanner stages of sexual development 2 (3)
pubic hair appears (pubarche)
testicle appears
breast buds form (thelarche)
Tanner stages of sexual development 3 (3)
pubic hair darkens and curls
inc penis size/length
inc breast size
Tanner stages of sexual development 4 (4)
inc penis width
darker scrotal skin
development of glans
raised areolae
Tanner stages of sexual development 5 (2)
adult
areolae no longer raised
2 phases of menstrual cycle
1. follicular phase: varies
2. luteal phase: 14 days (start w/ ovulation)
menstrual start 14 days after ovulation
event during follicular phase
1. 1 day after menses, FSH cause follicle to develop
2. estrogen slowly goes up
3. high level of estrogen: positive feed back for LH surge & ovulation
4. FSH also highest at the end of follicular phase
when is follicular growth fastest?
during 2nd week of proliferative phase
main events in luteal phase
1. corpus luteum release progesterone
2. if no fertilization, corpus luteum becomes corpus albicans
3. no more progesterone, menses
what phase in the uterus is associated w/ follicular phase? what hormone stimulates it?
proliferative phase
estrogen
what phase in the uterus is associated w/ luteal phase? what hormone is associated w/ it?
progesterone
maintains endometrium to support implantation; w/out progesterone, no implantation, menses starts
effect of dec progesterone on fertility
decrease
dysmenorrhea
pain w/ menses
often associated w/ endometriosis
oligomenorrhea
>35-day cycle
polymenorrhea
<21-day cycle
metorrhagia
frequent or irregular menstruation
menorrhagia
heavy menstrual bleeding
>80 mL blood loss or >7 days of menses
menometorrhagia
heavy, irregular menstrulation
oogenesis
figure
primary oocytes begin meiosis 1 when? complete it when?
fetal life
just prior to ovulation
oogenesis:
in what phase is meiosis 1 arrested and for how long?
prophase
for years until ovulation (primary oocytes)
oogenesis:
meiosis II is arrested at what stage and until what?
metaphase II
fertilization (secondary oocyte)
oogenesis:
when does the secondary oocyte degenerate?
if fertilization does not occur within 1 day
oogenesis:
primary oocyte divides into...
secondary (haploid) oocyte
polar body (may degenerate or give rise to 2 more polar bodies)
oogenesis:
secondary oocyte divides into...
ovum (haploid)
polar body
ovulation
endocrine
inc estrogen-->LH release--->ovulation (follicle rupture)
inc GnRH receptors on ant pituitary
progesterone induces inc temp
Mittelschmerz
transient mid-cycle ovulatory pain
classically associated with peritoneal irritation (e.g. follicular swelling/rupture, fallopian tube cotnraction)
can mimic appendicitis
timing and location of fertilization
upper end of fallopian tube (ampulla) within 1 day of ovulation
(most commonly)
timing and location of implantation
wall of uterus
6 days after fertilization
hCG becomes detectable when?
1 week after conception (blood)
2 weeks after conception (home test/urine)
(secreted by synctiotrophoblast)
lactation
stimulation
prolactin disinhibited by dec progesterone and estrogen after labor
suckling maintains production-->inc nerve stimulation = inc oxytocin, prolactin
prolactin
function
induces milk production
dec reproductive function
oxytocin
function
assists with milk letdown
promotes uterine contractions
important breast milk components
maternal Igs (esp IgA; passive immunity)
macrophages
lymphocytes
breast milk is ideal up until at least what age?
6 months
breast feeding is associated with a dec risk for...
asthma
allergies
diabetes mellitus
obesity
infections
maternal ovarian and breast cancer
supplementation with what is required for infants who are exclusively breastfed?
vit D
hCG
source
synctiotrophoblast
hCG
function
maintains corpus luteum/progesterone for first 8-10 weeks, acting like LH (otherwise no luteal stimulation-->abortion)
after the first 8-10 weeks, the corpus luteum degrades as the placenta produces its own...
estradiol and progesterone
hCG subunits
alpha: identical to that of LH, FSH, TSH
beta: unqiue (detected by pregnancy test)
hCG is increased with...
multiple gestations
hydatidiform nodes
choriocarcinomas
Down syndrome
hCG is decreased with...
ectopic/failing pregnancy
Edward syndrome
Patau syndrome
average age of menopause onset
51
(usually preceded by 4-5 years of abnormal cycles)
hormonal changes w/ menopause
dec estrogen
big inc FSH
inc LH (no surge)
inc GnRH
menopause before 40 yo may indicate...
premature ovarian failure
menopause causes...
HAVOCS:
hot flashes
atrophy of vagina
osteoporosis
coronary artery disease
sleep disturbances
what hormonal change is specific for menopause?
big inc FSH (loss of negative feedback on FSH due to dec estrogen)
source of estrogen after menopause? consequence?
estrone from peripheral conversion of androegns
inc androgens--->hirstutism
menopause
general definition
dec estrogen due to age-linked decline in number of ovarian follicles
spermatogenesis
figure
when and in what form do sperm precursors cross blood-testis barrier?
interphase I
spermatogonium
when does spermatogenesis begin?
puberty
full sperm development takes how long?
2 months
where does spermatogenesis occur?
seminiferous tubules
what happens, physically, to the sperm as it transformsinto a spermatozoan
loss of cytoplasmic contents
gain of acrosomal cap
effects of ciliary dyskinesia/Kartagener syndrome on sperm
impaired tail motility--->dec fertility
androgens
examples
testosterone
dihydrotestosterone (DHT)
androstenedione
androgens
source
DHT, testosterone = testes
androstenedione = adrenal gland
androgens
relative potency
DHT>testosterone>androstenedione
testosterone functions (5)
1. differentiation of epididymus, vas deferens, seminal v.s
2. growth spurt: penis, seminal v.s, sperm, muscles, RBCs
3. deepening of voice
4. closing of epiphyseal plates (via estrogen converted from testosterone)
5. libido
DHT
functions
early: differentiation of penis, scrotum, prostate
late: prostate growth, balding, sebaceous gland activity
enzyme and inhibitor:
testosterone--->DHT
5-alpha-reductase
inhibited by finasteride
what converts testosterone to estrogens in male?
where?
cytochrome P-450 aromatase
primarily adipose tissue and testes
effect of exogenous testosterone on male
--->inhibition of hypothalamic-pituitary-gonadal axis-->dec intratesticular testosterone--->dec testicular size--->azoospermia
who gets Klinefelter syndrome? how common is it?
male
1 in 850
what is Klinefelter syndrome karyotype? what chromosome does it have?
47 XXY w/ inactivated X chromosome (Barr body)
how does Klinefelter syndrome present? vignette will be associated w/ what?
1. progressive destruction & hyalinization of seminiferous - small, firm testes
2. sertoli cell damage - low inhibin
3. leydig cell damage - low testosterone
common cause for hypogonad; discover in infertility work up
Klinefelter syndrome has what FSH & LH level?
no negative feedback so high FSH, LH
(fa: may increase estrogen)
Klinefelter syndrome appearance
1. eunuchoid body shape
2. tall, long extremities
3. (uw) gynecomastia
4. may be developmental delay
who gets Turner syndrome?
female
what is Turner syndrome karyotype? how does it happen?
45 XO (complete monosomy - loss of paternal chromosome X)
45 XO/46XX (mosaicism)
mitosis or meiosis error
Turner syndrome is associated w/ what defects?
1. bicuspid aortic valve
2. coarctation of aorta w/ aortic root dilation (femoral < brachial pulse)
3. horseshoe kidney
what is the most common cause of primary amenorrhea?
Turner syndrome
pt may have menopause b/f menarche
Turner syndrome appearance
1. short stature (if untreated; inhibited long bone growth)
2. ovarian dysgenesis (streaky ovary)
3. shield chest (broad chest w/ wide nipples)
4. webbed neck (cystic hygroma)
5. lymphedema in hand & feet
Turner syndrome estrogen, FSH, LH level
low estrogen (from premature ovary failure)
high FSH, LH
Is Turner syndrome pregnancy possible?
yes
1. but likely to need oocyte donation
2. also need exogenous estradiol-17beta and progesterone
double Y males
sex
male
double Y males
genetics
XYY
random nondisjunction event (paternal meiosis II)
not inherited
double Y males
incidence
1:1000
double Y males
presentation
phenotypically normal (usually undiagnosed)
very tall
normal fertility
possibly associated with severe acne, learning disability, autism spectrum disorders
what is true hermaphroditism genotypes? how does it present?
46XX; 46XY rare
both ovary & testicle are present (aka ovotestis; previously called true hermaphroditism)
diagnosing disorders of sex chromosomes: LH & testosterone level of defective androgen receptor
LH: high
testosterone: high
diagnosing disorders of sex chromosomes: LH & testosterone level of testosterone-secreting tumor & steroid use
LH: low
testosterone: high
diagnosing disorders of sex chromosomes: LH & testosterone level of primary hypognoadism
LH: high
testosterone: low
diagnosing disorders of sex chromosomes: LH & testosterone level of hypogonadotrophic hypogonadism
LH: low
testosterone: low
e.g. Kallmann syndrome
(hypogonadotrophic hypogonadism = central or secondary hypogonadism; low GnRH)
3 terms that refer to disagreement between phenotypic (external genitalia) and gonadal (testes vs. ovaries) sex
pseudohermaphrodite
intersex
hermaphrodite
female pseudohermaphrodite
genotype
46, XX DSD (disorder of sex development)
female pseudohermaphrodite
presentation
1. normal internal genitalia (ovaries ok)
2. external genitalia virilized or ambiguous e.g. clitoromegaly
female pseudohermaphrodite
cause; (uw) 3 examples
excessive exposure to androgenic steroids during early gestation
1. fetus: aromatase deficiency; mom's virilization
2. fetus/infant: congenital adrenal hyperplasia; mom's normal b/c placental aromatase activity is ok
3. exogenous androgens
male pseudohermaphrodite
genotype
46, XY DSD (disorder of sex development)
male pseudohermaphrodite
presentation
1. testes present
2. external genitalia female or ambiguous
male pseudohermaphrodite
most common form
androgen insensitivity syndrome (testicular feminization)
placenta aromatase deficiency
inability to synthesize estrogens from androgens
masculinization of female (46,XX) infants (ambiguous genitals)
inc serum testosterone and androstenedione
aromatase deficiency
can present with...
maternal virilization during pregnancy (fetal androgens cross placenta)
androgen insensitivity syndrome
genotype
(46,XY)
androgen insensitivity syndrome
description
defect in androgen receptor--->normal-appearing female
female external genitalia
scant pubic hair
rudimentary vagina
fallopian tubes and uterus absent
testes develop, usually within labia majora (surgically removed to prevent malignancy)
androgen insensitivity syndrome
hormone levels
inc testosterone, estrogen, LH (vs. sex chromosome disorders)
5-alpha-reductase deficiency
genetics
AR
sex limited to genetic males (46,XY)
5-alpha-reductase deficiency
description
inability to convert testosterone to DHT
genitalia ambiguous until puberty--->inc testosterone = masculinization/inc growth of external genitalia
internal genitalia normal
5-alpha-reductase deficiency
hormone levels
testosterone, estrogen normal
LH normal or inc
what causes Kallmann syndrome?
GnRH-secreting neuron in olfactory placode fail to migrate to hypothalamus
(so no GnRH, a type of hypogonadotropic hypogonadism)
Kallmann syndrome's presentation
1. delayed puberty & infertility (no sperm, no mensus)
2. cannot smell i.e. asomnia
Kallmann syndrome hormone levels (4)
GnRH, FSH, LH, testosterone are low
hydatidiform mole
cystic swelling of chorionic villi and proliferation of chorionic epithelium (only trophoblast)
hydatidiform mole
associated with
theca-lutein cysts
hyperemesis gravidarum
hyperthyroidism
hydatidiform mole
treatment
dilation and curettage and MTX
hydatidiform mole
monitor..?
beta-hCG
hydatidiform mole: complete mole
karyotype
46,XX or 46,XY
hydatidiform mole: complete mole
hCG
huge inc
hydatidiform mole: complete mole
uterine size
inc
hydatidiform mole: complete mole
components
most commonly enucleated egg+single sperm (subsequently duplicates parental DNA)
hydatidiform mole: complete mole
risk of complications
15-20%
malignant hypertrophoblastic disease
hydatidiform mole: complete mole
symptoms
first-trimester bleeding
enlarged uterus
hyperemesis
pre-eclampsia
hyperthyroidism
hydatidiform mole: complete mole
imaging
"honeycombed" uterus or "clusters of grapes" on ultrasound
hydatidiform mole: partial mole
karyotype
69,XXX or 69,XXY or 69,XYY
hydatidiform mole: partial mole
hCG
inc
hydatidiform mole: partial mole
uterus size
normal
hydatidiform mole: partial mole
convert to choriocarcinoma?
rare
hydatidiform mole: complete mole
convert to choriocarcinoma?
2%
hydatidiform mole: partial mole
fetal parts
yes
hydatidiform mole: complete mole
fetal parts
no
hydatidiform mole: partial mole
components
2 sperm + 1 egg
hydatidiform mole: partial mole
risk of complications
low risk of malignancy (<5%)
hydatidiform mole: partial mole
symptoms
vaginal bleeding
abdominal pain
hydatidiform mole: partial mole
imaging
fetal parts
gestational hypertension (pregnancy-induced hypertension)
characteristics
>150/90 mmHg after 20th week of gestation
no preexisting hypertension
no peoteinemia or end-organ damage
gestational hypertension (pregnancy-induced hypertension)
treatment
antihypertensives (alpha-methyldopa, labetalol, hydralazine, nifedipine)
deliver at 37-39 weeks
preeclampsia
new-onset hypertension with either proteinuria or end-organ dysfunction after 20th week of pregnancy
may proceed to eclampsia or HELLP syndrome
new-onset hypertension with either proteinuria or end-organ dysfunction before 20th week of pregnancy suggests...
molar pregnancy
preeclampsia
cause
abnormal placental spiral arteries--->endothelial dysfunction, vasoconstriction, ischemia
preeclampsia
treatment
antihypertensives
IV magnesium sulfate (to prevent seizure)
definitive is delivery of fetus
preeclampsia
incidence inc in pts w/...
pre-existing hypertension
diabetes
chronic renal disease
AI disorders
preeclampsia
complications
placental abruption
coagulopathy
renal failure
uteroplacental insufficiency
eclampsia
eclampsia
preeclampsia + maternal seizures
eclampsia
cause of maternal death
stroke, intracranial hemorrhage, or ARDS
eclampsia
treatment
IV magnesium sulfate
antihypertensives
immediate delivery
HELLP syndrome
treatment
immediate delivery
HELLP syndrome
stands for...
Hemolysis
Elevated Liver enzymes
Low Platelets
HELLP syndrome
a manifestation of severe preeclampsia
HELLP syndrome
blood smear shows___
schistocytes
HELLP syndrome
can lead to___
hepatic subcapsular hematomas--->rupture--->severe hypotension
placental abruption (abruptio placentae)
premature separation (partial or complete) of placenta from uterine wall before delivery of infant
life threatening for mother and fetus
placental abruption (abruptio placentae)
risk factors
trauma (e.g. car accident)
smoking
hypertension
preeclampsia
cocaine use
placental abruption (abruptio placentae)
presentation
abrupt, painful bleeding (concealed or apparent) in third trimester
possible DIC, maternal shock, fetal distress
placenta accreta/increta/percreta
cause
defective decidual layer--->abnormal attachment and separation after delivery
3 types distinguished by depth of penetration
placenta accreta/increta/percreta
risk factors
prior C-section
inflammation
placenta previa
placenta accreta/increta/percreta
accreta:
placenta attaches to myometrium without penetrating it
most common
placenta accreta/increta/percreta
increta
placenta penetrates into myometrium
placenta accreta/increta/percreta
percreta
placenta penetrates through myometrium, into uterine serosa (invades entire uterine wall)
placenta may attach to rectum or bladder
placenta accreta/increta/percreta
presentation
often detected on ultrasound prior to delivery
no separation of placenta after delivery--->postparum bleeding (can cause Sheehan syndrome)
placenta previa
attachment of placenta to lower uterine segment over or < 2cm from internal cevical os
placenta previa
risk factors
multiparity
prior C-section
placenta previa
associated with
painless 3rd trimester bleeding
vasa previa
fetal vessels run over, or in close proximity to, cervical os
vasa previa
complications
vessel rupture
exsanguination
fetal death
emergency C-section usually indicated
vasa previa
presentation
triad of membrane rupture
painless vaginal bleeding
fetal bradycardia (<110 beats/min)
vasa previa
associated with
velamentous umbilical cord insertion (insertion in chorioamniotic membrane rather than placenta)---fetal vessels travel to placenta unprotected by Wharton jelly
retained placental tissue
may cause postpartum hemorrhage
inc risk of infection
ectopic pregnancy
most common location
ampulla of fallopian tube
ectopic pregnancy
suspect with....
history of amenorrhea
lower than expected hCG based on dates
sudden abdominal pain (with or without bleeding
ectopic pregnancy
confirm with...
utlrasound
ectopic pregnancy
often mistaken for clinically as...
appendicitis
ectopic pregnancy
risk factors
history of infertility
salpingitis (PID)
ruptured appendix
prior tubal surgery
polyhydramnios
too much (>1.5-2L) amniotic fluid
polyhydramnios
associated with...
fetal malformations (e.g. esophageal/duodenal atresia, anencephaly) resulting in inability to swallow amniotic fluid
maternal diabetes
fetal anemia
multiple gestations
oligohydramnios
too little (<0.5 L) amniotic fluid
oligohydramnios
associated with..
placental insufficiency
bilateral renal agenesis
posterior urethral valves (in males) and resultant inability to excrete urine
profound oligohydramnios can cause....
Potter sequence
gynecologic tumor epidemiology
US: endometrial>ovarian>cervical
worldwide: cervical most common due to lack of screening/HPV vaccination
worst prognosis: ovarian>cervical>endometrial
squamous cell carcinoma (SCC) of vagina
primary: rare
secondary: to cervical SCC
clear cell adenocarcinoma of vagina
affects women who had exposure to DES in uterus
sarcoma botyoides of vagina (rhabdomyosarcoma variant)
affects girls < 4 yo
spindle-shaped cells
desmin +
clear, grape-like, polyploid mass emerging from vagina
cervical dysplasia and carcinoma in situ
disordered epithelial growth, beginning at basal layer of squamocolumnar junction and spreading outward
classified as CIN-1,-2,-3 (severe dysplasia or carcinoma in situ) depending on extent of dysplasia
cervical dysplasia and carcinoma in situ
associated with...
HPV 16
HPV 18
(produce E6 gene product - inhibits p53 suppressor gene - and E7 gene product - inhibits RB suppressor gene)
cervical dysplasia and carcinoma in situ
may progress to ___ if untreated
invasive carcinoma
cervical dysplasia and carcinoma in situ
presentation
typically asymptomatic (detected with Pap smear) or as abnormal vaginal bleeding (often postcoital)
cervical dysplasia and carcinoma in situ
risk factors
#1 is multiple sexual partners
smoking
starting sexual intercourse at young age
HIV infection
invasive carcinoma of cervix
often squamous cell carcinoma
Pap smear: cervical dysplasia (koilocytes) before progression to invasive carcinoma
lateral invasion can block ureters--->renal failure
invasive carcinoma of cervix
diagnosis
via colposcopy and biopsy
premature ovarian failure
premature atresia of ovarian follicles in women of reproductive age
signs of menopause after puberty and before 40 yo
dec estrogen, inc LH, FSH
most common causes of anovulation
pregnancy
polycystic ovarian syndrome
obesity
HPO axis abnormalities
premature ovarian failure
hyperprolactemia
thyroid disorders
eating disorders
competitive athletics
Cushing syndrome
adrenal insufficiency
Stein-Leventhal syndrome
aka
polycystic ovarian syndrome
polycystic ovarian syndrome
hyperinsulinemia and/or insulin resistance--->hypothalamic hormonal feedback response altered--->inc FSH/LH, inc androgens from theca interna cells, dec rate follicular maturation--->unruptured follicles (cysts) + anovulation
polycystic ovarian syndrome
common cause of...
subfertility
polycystic ovarian syndrome
presentation
enlarged, bilateral cystic ovaries
amenorrhea/oligomenorrhea
hirstutism
acne
subfertility
polycystic ovarian syndrome
associated with...
obesity
inc risk endometrial cancer secondary to unopposed estrogen from repeated anovulatory cycles
polycystic ovarian syndrome
treatment
weight reduction
OCPs
clomiphene citrate
ketoconazole
spironolactone
ovarian cysts: follicular
distension of unruptured graafian follicle
may be associated with hyperestrogenism, endometrial hyperplasia
most common ovarian mass in young women
ovarian cysts: theca-lutein
often bilateral/multiple
due to gonadotropin stimulation
associated with choriocarcinoma and hydatidiform moles
most common adnexal mass in women >55 yo
ovarian neoplasm
most common malignant ovarian neoplasm
epithelial origin, esp serous cystadenocarcinoma
ovarian neoplasm
risk factors
inc age
infertility
hereditary nonpolyposis colorectal cancer (HNPCC)
strong family history
ovarian neoplasm
dec risk associated with...
previous pregnancy
history of breastfeeding
OCPs
tubal ligation
ovarian neoplasm
general presentation
adnexal mass
abnormal distension
bowel obstruction
pleural effusion
diagnosis of ovarian neoplasm
surgically
ovarian neoplasm
monitor what lab value?
CA 125 levels (not good for screening though)
benign ovarian neoplasms:
serous cystadenoma
most common ovarian neoplasm
lined with fallopian tube-like epithelium
often bilateral
benign ovarian neoplasms:
mucinous cystadenoma
multiloculated
large
lined by mucus-secreting epithelium
benign ovarian neoplasms:
endometrioma
endometriosis within ovary w/ cyst formation
pelvic pain, dysmenorrhea, dysparemia
symptoms vary with menstrual cycle
complex mass on ultrasound
"chocolate cyst" - endometrioma filled with dark, redish-brown blood
benign ovarian neoplasms:
mature cystic teratoma (dermoid cyst)
germ cell tumor
most common 20-30 yo
cystic mass w/ elements from all 3 germ layers (e.g. teeth, hair, sebum)
pain secondary to ovarian enlargement or torsion
may contain thyroid tissue/present as hyperthyroidism (struma ovarii)
benign ovarian neoplasms:
Brenner tumor
looks like bladder
solid tumor; pale yellow-tan; appears encapsulated
"coffee bean" nuclei on H&E stains
benign ovarian neoplasms:
fibromas
bundles of spindle-shaped fibroblasts
pulling sensation in groin
Meigs syndrome
triad of ovarian fibroma, atrasia, hydrothorax
benign ovarian neoplasms:
thecoma
like granulosa cell tumors
may produce estrogen
usually presents as abnormal uterine bleeding in postmenopausal women
malignant ovarian neoplasms:
immature teratoma
aggressive
contains fetal tissue, neuroectoderm
typically represented by immature/embryonic-like renal tissue
mature teratoma more likely to contain thyroid tissue
malignant ovarian neoplasms:
granulosa cell tumor
presentation and who
most common malignant stromal tumor
women > 50yo
produces estrogen and/or progesterone
abnormal uterine bleeding, sexual precocity (pre-adolescents), breast tenderness
malignant ovarian neoplasms:
granulosa cell tumor
histology
Call-Esner bodies (granulosa cells haphazardly arranged around collections of eosinophilic fluid, resembling primordial follicles)
malignant ovarian neoplasms:
serous cystedenocarcinoma
most common ovarian neoplasm
usually bilateral
psammoma bodies
malignant ovarian neoplasms:
mucinous cystadenocarcinoma
pseudomyxoma peritonei - intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor
malignant ovarian neoplasms:
dysgerminoma
adolescents
rarer, but female equivalent of male seminoma
1% of ovarian tumors, 30% of germ cell tumors
sheets of uniform "fried egg" cells
tumor markers = hVG, LDH
malignant ovarian neoplasms:
choriocarcinoma
rare
develops during or after pregnancy in mother or baby
malignancy of chorionic tissue (cytotrophoblasts, syncytiotrophoblasts)
no chorionic villi present
inc frequency of bilateral/multiple theca-lutein cysts
very responsive to chemo
malignant ovarian neoplasms:
choriocarcinoma presentation
abnormal inc beta-hCG
shortness of breath
hemoptysis
malignant ovarian neoplasms:
choriocarcinoma
spread
hemotgenously
malignant ovarian neoplasms:
yolk-sac (endodermal sinus) tumor
aggressive
in ovaries (or testes) and sacrococcygeal area in young children
most common tumor in male infants
yellow, friable (hemorrhagic), solid mass
50% have Chiller-Duval bodies (resemble glomeruli)
AFP = tumor marker
malignant ovarian neoplasms:
Krukenberg tumor
GI malignancy that metastasizes to ovaries--->mucin-secreting signet cell adenocarcinoma
endometrial polyp
well-circumscribed collection of endometrial tissue in uterine wall
may contain SM cells
can extend into endometrial cavity in form of polyp
endometrial conditions:
leiomyoma (fibroid)
most common tumor in females
multiple discrete tumors
inc incidence in blacks
benign SM tumor; malignant transformation rare
estrogen sensitive: tumor size inc w/ pregnancy, dec w/ menopause
peak occurence 20-40 yo
endometrial conditions:
leiomyoma presentation
asymptomatic or
abnormal uterine bleeding
miscarriage
endometrial conditions:
leiomyoma complications
severe bleeding--->Fe-def anemia
rare progression to leiomyosarcoma
endometrial conditions:
leiomyoma histology
whorled pattern of SM bundles w/ well-demarcated borders
endometrial conditions:
adenomyosis
extension of glandular endometrial tissue into uterine myometrium
due to hyperplasia of basal layer of endometrium
endometrial conditions:
adenomyosis presentation
dysmenorrhea
menorrhagia
uniformly enlarged, soft, globular uterus
endometrial conditions:
adenomyosis treatment
GnRH agonists
hysterectomy
endometrial conditions:
endometriosis
non-neoplastic, endometrial glands/stroma outside endometrial cavity
can be anywhere (ovary (bilateral), pelvis, peritoneum most common)
in ovary, appears as blood-filled "chocolate cyst"\
endometrial conditions:
endometriosis
possible causes
retrograde flow
metaplastic transformation of multipotent cells
transportation of endometrial tissue via lymphatic system
endometrial conditions:
endometriosis
characterized by...
cyclic pelvic pain
bleeding
dysmenorrhea
dyspareunia
dyschezia (pain w/ defecation)
infertility
normal-sized uterus
endometrial conditions:
endometriosis
treatment
NSAIDs
OCPs
progestins
GnRH agonists
danazol
laparoscopic removal
endometrial conditions:
endometritis
associated with...
retained products of conception following delivery, miscarriage, or abortion
foreign body (e.g. IUD)
retained material promotes infection by bacterial flora from vagina or intestinal tract
endometrial conditions:
endometritis
treatment
gentamicin + clindamycin w/ or w/o ampicillin
endometrial conditions:
endometrial hyperplasia
abnormal endometrial gland proliferation
usually caused by excess estrogen stimulation
endometrial conditions:
endometrial hyperplasia
inc risk for...
endometrial carcinoma
endometrial conditions:
endometrial hyperplasia
presentation
postmenopausal vaginal bleeding
endometrial conditions:
endometrial hyperplasia
risk factors
anovulatory cycles
hormone replacement therapy
polycystic ovarian syndrome
granulosa cell tumor
endometrial conditions:
endometrial carcinoma
most common gynecologic malignancy
peak occurrence: 55-65 yo
presents w/ vaginal bleeding
endometrial conditions:
endometrial carcinoma
usually preceded by...
endometrial hyperplasia
endometrial conditions:
endometrial carcinoma
risk factors
prolonged use of estrogen w/o progestins
obesity
diabetes
hypertension
multiparity
late menopause
Lynch syndrome
breast pathology affecting
1. nipple
nipple
1. Paget
2. breast abscess
duct
1. intraductal papilloma
2. abscess, mastitis
major ducts
1. fibrocystic change
2. ductus carcinoma in situ
3. invasive ductal carcinoma
terminal duct
1. tubular carcinoma
lobules
1. lobular carcinoma
benign breast tumors:
intraductal papilloma
characteristics
small tumor that grows in lactiferous ducts
typically beneath areola
serous or bloody nipple discharge
slight (1.5-2X) inc risk for carcinoma
proliferative breast disease
most common cause of "breast bumps" from 25-menopause
fluctuation in mass size
usually does not indicate inc risk carcinoma
proliferative breast disease
presentation
premenstrual breast pain
multiple, often bilateral lesions
proliferative breast disease - histologic types
fibrous
hyperplasia of breast stroma
proliferative breast disease - histologic types
cystic
fluid filled
blue dome
ductal dilation
proliferative breast disease - histologic types
sclerosing adenosis
inc acini, intralobular fibrosis
associated w/ calcifications
often confused w/ cancer
inc (1.5-2x) risk of developing cancer
proliferative breast disease - histologic types
epithelial hyperplasia
inc # epithelial cell layers in terminal duct lobule
inc risk carcinoma w/ atypical cells
women > 30yo
lactational mastitis
during breastfeeding
inc risk bacterial infection through cracks in nipple
S. aureus most common
treat: dicloxacillin and continued breastfeeding
(breast) fat necrosis
benign, usually painless lump forms as result of injury to breast tissue
mammogram: abnormal calcification
biopsy: necrotic fat, giant cells
up to 50% pts may not resport trauma
gynecomastia
breast enlargement in males
physiologic (not pathologic) at birth, puberty, old age
gynecomastia
causes
hyperestrogenism (cirrhosis, testicular tumor, puberty, old age)
Klinefelter syndrome
drugs (spinonolactone, digoxin, cimetidine, alcohol, ketoconazole)
malignant breast tumors:
commonly appear when?
after menopause
malignant breast tumors:
most common location
upper-outer quadrant of breast
penile pathology:
Peyronia disease
abnormal curvature of penis due to fibrous plaque in tunica albunginea
associated w/ erectile dysfunction
can cause pain, anxiety
consider surgical repair once curvature stabilizes
=/ penile fracture (rupture of corpus cavernosa due to forced bending)
penile pathology:
priapism
painful sustained erection lasting > 4 hrs
penile pathology:
priapism
associated with
trauma
sickle cell disease (sickled RBCs get trapped in vascular channels)
medications (eg. sildenafil, trazodone)
penile pathology:
priapism
treatment
immediately treat:
corporal aspiration
intracavernosal phenylephrine
surgical decompression to prevent ischemia
penile pathology:
squamous cell carcinoma
where most common?
Asia, Africa, South America
penile pathology:
squamous cell carcinoma
precursor
in situ lesions:
Bowen disease (in penile shaft; presents as leukoplakia)
erythroplasia of Queyrat (cancer of glans; presents as erythroplakia)
Bowenoid papulosis (carcinoma in situ of unclear malignant potential, presenting as reddish papules)
penile pathology:
squamous cell carcinoma
associated with
HPV
lack of circumcision
extragonadal germ cell tumors (male)
where?
various locations, including (in adults): retroperitoneum, mediastinum, pineal, and supracellar regions
(infants/children): sacrococcygeal teratomas most common
scrotal masses
presentation
benign scrotal lesions present as testicular masses that can be transilluminated (vs. solid testicular tumors)
scrotal masses
spermatocele
cyst due to dilated epididymal duct or rete testis
paratesticular fluctuant nodule
testicular germ cell tumors
incidence
95% of all testicular tumors
usually in young men
may present as mixed germ cell tumor
testicular germ cell tumors
seminoma
malignant, painless, homogenous testicular enlargement
most common testicular tumor
most common in 3rd decade, never in infancy
late mestastasis; excellent prognosis
radiosensitive
testicular germ cell tumors
seminoma
labs and histology
inc placental ALP
large cells in lobules w/ watery cytoplasm and "fried egg" appearance
testicular germ cell tumors
yolk sac (endodermal sinus) tumor
yellow, mucinous
aggressive, malignant
Schiller-Duval bodies resemble primitive glomeruli
inc ALP highly characteristic
most common testicular tumor in boys < 3 you
yolk sac (endodermal sinus) tumor
testicular germ cell tumors
choriocarcinoma
malignant
inc hCG
disordered synctiotrophoblastic and cytotrophoblastic elements
testicular germ cell tumors
choriocarcinoma
spread
hematogenous ---> lungs and brain
(may present w/ "hemorrhagic stroke" due to bleeding into metastasis
testicular germ cell tumors
choriocarcinoma
may cause...
gynecomastia
symptoms of hyperthyroidism (hCG is structurally similar to LH, FSH, TSH)
testicular germ cell tumors
teratoma
mature teratoma may be malignant (unlike in females)
benign in children
50% cases have inc hCG and/or AFP
testicular germ cell tumors
embryonal carcinoma
malignant, hemorrhagic mass w/ necrosis
painful
worse prognosis than seminoma
glandular/papillary morphology usually
"pure" form rare; commonly w/ other tumor types
pure: inc hCG, normal AFP (inc in mixed form)
5% of all testicular tumors are ___
testicular non-germ cell tumors, which are mostly benign
testicular non-germ cell tumors
Leydig cell
contain Reinke crystals (eosinophilic cytoplasmic inclusions)
usually produce androgens
gynecomastia (men), prococious puberty (boys)
golden brown color
testicular non-germ cell tumors
Sertoli cell
androblastoma from sex cord stroma
testicular non-germ cell tumors
testicular lymphoma
most common testicular cancer in older men
not primary; arises from mestastatic lymphoma to testes
aggressive
benign prostatic hyperplasia
who?
common in men > 50 yo
benign prostatic hyperplasia
characterized by
smooth, elastic, firm nodular enlargement (hyperplasia, not hypertrophy) of periurethral (lateral and middle) lobes, which compresses urethra into a vertical slit
not premalignant
benign prostatic hyperplasia
presentation
inc frequency of urination
nocturia
difficulty starting/stopping urine flow
dysuria
benign prostatic hyperplasia
complications
distension
bladder hypertrophy
hydronephrosis
UTIs
inc free prostate-specific antigen (PSA)
benign prostatic hyperplasia
treatment
alpha-1 antagonists (terazosin, tamsulosin)--->SM relaxation
5-alpha reductase inhibitors (e.g. finasteride)
PDE-5 inhibitors
prostatitis
dysuria, frequency, urgency; low back pain
acute: bacterial (e.g. E. coli)
chronic: bacterial or abacterial (most common)
prostastic adenocarcinoma
who?
common in men > 50 yo
prostastic adenocarcinoma
tumor markers
prostatic acid phosphatase (PAP)
PSA (total inc; dec fraction of free PSA)
what is a triple test and when is it done
done at week 16 - 18 gestation for
1. Alpha-fetoprotein
2. hCG
3. estriol level
what is the next step to cofirm abnormal triple test
fetal ultrasound (USG)
(if USG is normal & no abnormal anatomy; then amniocentesis)
what is alpha-fetoprotein? what is the most common cause for high AFP?
protein made by fetus liver, GI, yolk sac
most common cause for wrong reading: data error
what syndromes are associated w/ high AFP (3) & low AFP (1)?
high:
neural tube defects
abd wall defects
multiple gestation
low:
Down's syndrome
low estriol in a triple test suggests
placental insufficiency
increase hCG in triple test suggests
1. multiple gestation
2. hydatidiform mole
3. choriocarcinoma
(made by trophoblast tissue)
(uw) motor nerves innervating pelvis
L3-L4 obturator: adduction
L5-S2 inferior gluteal: gluteus maximus
S2-4 pudendal: urethral & anal sphincters
(uw) sensory nerves innervating pelvis
T12-L1 Iliohypogastric: suprapubic:
L1-2 genitofemoral: scrotum, labia majora, thigh
L2-3 anterior & lateral thigh
L3-L4 medial thigh
S2-4 pudendal: perineum
(uw) landmarks for pudendal nerve block
1. ischial spine: bony protrusion posterolateral to vaginal sidewall
2. sacrospinous ligament
inject intravaginal anesthetic medially close to ischial spine through sacrospinous ligament
(uw) what vessels can be perforate by pundendal block (2)
internal pudendal a.
inferior gluteal a.
medial to pudendal nerve
pharm: 5 steps in female hormone synthesis
1. hypothalamus - GnRH
2. ant. pituitary - LH, FSH
3. (LH, P450) theca cells - androgen
4. (FSH, aromatase) granulosa cell - turns androgen to estrogen
5. (estrogen matures oocyte) follicle - progesterone
pharm: rx controlling reproductive hormones
1. selective estrogen receptor antagonist in hypothalamus: Clomiphene
2. GnRH analog: Leuprolide
3. P450 inhibitor reducing androgen production: ketoconazole
4. Androgen analog: oral contraceptive, danazol
5. aromatase inhibitor reducing androgen conversion to estrogen:
anastrozole, letrozole, exemstane
6. selective estrogen receptor modulators: tamoxifen, raloxifene
7. estrogen analog + hormone replacement therapy
8. progestin
9. anti-progestin: mifepristone, ulipristal
10. labor: terbutaline, ritodrine
pharm: 4 steps in male hormone synthesis
1. hypothalamus - GnRH
2. ant. pituitary - LH, FSH
3. (LH, P450) Leydig cells - testosterone
4. (5-alpha aromatase) stromal cells - testosterone to dihydrotestosterone DHT
pharm: rx controlling reproductive hormone
1. CYP450 inhibitor inhibiting testosterone: ketoconazole, spironolactone
2. testosterone, methyltestosterone
3. 5-alpha reductase inhibitor blocking conversion of testosterone to DHT: finasteride
4. androgen receptor inhibitor: flutamide, cyproterone, spironolactone
pharm: selective estrogen receptor modulator in hypothalamus example
clomiphene
pharm: selective estrogen receptor modulator - clomiphene mechanism
1. antagonist at estrogen receptors in hypothalamus
2. prevents normal feedback inhibition
3. increase release LH, FSH from pituitary - stimulate ovulation
pharm: selective estrogen receptor modulators - clomiphene indication
infertility due to anovulation (e.g. PCOS)
pharm: selective estrogen receptor modulators - clomiphene side-effects (4)
1. hot flashes
2. ovarian enlargement
3. multiple simultaneous pregnancy
4. visual disturbance
pharm: GnRH analogue example (mnemonic)
leuprolide (used in "lieu" of GnRH)
pharm: GnRH analog mechanism (2)
pulsatile: agonist (up FSH, LH)
continuous: antagonist (lower FSH, LH)
pharm: GnRH analog indication (3)
pulsatile: infertility
tonic:
1. prostate cancer (w/ flutamide)
2. uterine fibroids
3. precocious puberty
(long acting GnRH analog can cause transient rise in LH & testosterone; using flutamide limit the tumor stimulating effect)
pharm: GnRH analog side effect (2)
1. antiandrogen
2. n/v
pharm: androgen analog example & mechanism
danazol: partial agonist at androgen receptors
pharm: androgen analog indication (2)
1. endometriosis
2. hereditary angioedema
pharm: androgen analog side effects
(hint: think androgen-3, think steroid-1, what organ & outcome-2, low level-1)
1. masculinity
2. hirstutism
3. acne
4. weight gain
5. liver toxicity
6. edema
7. decrease HDL
pharm: aromatase inhibitors examples (2)
anastrozole
exemestane
pharm: aromatase inhibitor mechanism
inhibit peripheral conversion of androgen to estrogen
pharm: aromatase indication
postmenopausal women w/ estrogen receptor positive breast cancer
pharm: selective estrogen receptor modulators - tamoxifen mechanism
antagonist: breast
agonist: bone, uterus
pharm: selective estrogen receptor modulators - tamoxifen indication (2)
1. treat + prevent estrogen-progesterone receptor ER/PR positive breast cancer
2. (uw) prevent breast enlargement in androgen deprived therapy ADT
pharm: selective estrogen receptor modulators - tamoxifen side effect (2)
1. blood clot
2. higher risk endometrial cancer
pharm: selective estrogen receptor modulators - raloxifene mechanism
antagonist: breast, uterus: estrogen
agonist: bone
pharm: selective estrogen receptor modulators - raloxifene indication
osteoporosis
pharm: selective estrogen receptor modulators - ralixifene
side-effect
blood clot but not endometrial cancer (vs. tamoxifen)
pharm: synthetic estrogens examples (3)
1. estradiol
2. DES
3. mestranol
pharm: synthetic estrogens indication (3-female, 1-male)
1. hypogonadism or ovarian failure
2. menstrual abnormality
3. postmenopausal hormone replacement
4. men: androgen dependent prostate cancer
pharm: synthetic estrogens side effect (higher risk-1, higher cancer risk-2, syptom-1)
1. higher risk endometrial cancer
2. bleeding in postmenopausal women
3. clear cell adeonocarinoma of vagina in women w/ DES exposure in utero
4. higher risk blood clot
pharm: synthetic estrogens contraindication (2)
1. estrogen receptor positive breast cancer
2. DVTs
pharm: hormone replacement therapy indication
prevent menopausal symptoms
osteoporosis (increase estrogen, inhibits osteoclast)
pharm: why is progesterone added to estrogen hormone replacement therapy? possible complication?
1. unopposed estrogen therapy causes higher risk of endometrial cancer
2. complication: higher cardiovascular risk
pharm: progestin binds progesterone receptor to cause what effect (3)
endometrium
1. decrease growth
2. increase vascularization
3. thickens cervical mucus
pharm: progestins indication (3)
1. oral contraceptive
2. endometrial cancer
3. abnormal uterine bleeding
pharm: what is progestin challenge (3)
pt w/ amenorrhea is given progestin
1. bleeding: amenorrhea d/t no ovulation
2. no bleeding; amenorrhea d/t low estrogen or outflow check issues e.g. Asherman syndrome
pharm: anti-progestin example (2)
mifepristone
ulipristal
pharm: anti-progestin
mechanism
blocks progestins at progesterone receptors
pharm: anti-progestin indication
mifespristone:
termination of pregnancy
administered w/ misoprostol (PGE1)
ulipristal:
emergency contraception
pharm: combined oral contraception mechanism (3)
estrogen + progestin
1. inhibit LH/FSH surge (LH, FSH = gonadotropin)
2. no estrogen surge > no LH surge > no ovulation
3. decrease ovary androgen production
progestins: thicken cervical mucus (block sperm), inhibit endometrial proliferation (embryo can't implantation)
pharm: combined oral contraception additional indications: (2)
1. polycystic ovary syndrome PCOS
2. hirtuism
pharm: combined oral contraception
contraindications (3)
1. smokers >35 yo
2. history of CVA & thromboembolism
3. history of estrogen-dependent tumor
pharm: beta 2 agonist example & action (indication)
1. terbutaline
2. ritodrine
relax uterus to slow contraction
pharm: polycystic ovarian syndrome PCOS rx example (2)
ketoconazole: inhibits CYPc17
spironolactone:
1. antagonist-androgen receptor
2. agonist-progesterone receptor
3. inhibits CYPc17 & 17 alpha-hydroxylase
pharm: polycystic ovarian syndrome PCOS rx side effect
1. gynecomatia
2. amenorrhea
pharm: testosterone, methyltestosterone
mechanism
agonists at androgen receptors
pharm: testosterone, methyltestosterone indication (3)
1. treat hypogonadism
2. development of secondary male sex characteristics
3. stimulation of anabolism to promote recovery after burn or injury
pharm: testosterone, methyltestosterone side effects (masculinization + 2, level up - 1, level down - 1)
1. gonadal atrophy: negative feedback inhibits LH release
2. premature closure of epiphyseal plates
3. inc LDL
4. dec HDL
pharm: enzyme that converts testosterone to dihydrotestosterone. what is the difference b/w 2 hormone?
5-alpha-reductase
DHT is more potent
pharm: 5 alpha reductase inhibitor example & action
finasteride
inhibit 5 alpha reductase so testosterone cannot convert into DHT
(uw: takes 6-12 mo)
pharm: 5 alpha reductase inhibitor indication
1. BPH
2. male pattern baldness
(pt w/ adreogenetic alopecia has high level of 5 alpha reductase & more androgen receptors, reducing enzyme level helps w/ alopecia)
(uw) abuse of androgen, androgen precursor & agent increasing androgen production will do what to hematocrit
low hematocrit
pharm: non-steroid androgen receptor competitive inhibitor example.
flutamide
pharm: non-steroid androgen receptor competitor inhibitor indication
prostate carcinoma
pharm: alpha-1 antagonist example. What specific receptor does it act on?
tamsulosin
specific for alpha (1A,D) receptors on prostate
pharm: alpha-1 antagonist indication
treat BPH by inhibiting SM contraction
pharm: phosphodiesterase type 5 PDE-5 inhibitor (3); what pathway does it work on
mechanism
1. sildenafil
2. verdenafil
3. tadalafil
inhibit phosphodiesterase PDE-5 to inc cGMP, SM releaxation in corpus cavernosum, inc blood flow, penile erection
pharm: phosphodiesterase type 5 PDE-5 mechanism
1. inhibit PDE-5 & increase cGMP
2. prolong smooth muscle relaxation in response to NO
3. increase blood flow to penis corpus cavernosum
4. decrease pulmonary vascular resistance
pharm: phosphodiesterase type 5 PDE-5 indication (3)
1. erectile dysfunction
2. pulmonary HTN
3. (tadalafil) BPH
pharm: phosphodiesterase type 5 side effect (highest risk, think vasodilation-2, GI-1, eyesight-1)
1. life-threatening hypotension
2. headache
3. vasodilation
4. dyspepsia
5. cyanopsia (blue-tinted vision)
pharm: direct arteriole vasodilator example (1) & indication (2)
minoxidil
1. androgenic alopecia
2. severe refractory HTN
(uw) pharm: 2 components of ovulation induction therapy
1. short course of menotropins (mimic FSH to trigger follicle)
2. hCG injection (mimics LH surge)
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