Reproduction Flashcards
1
Q
sonic hedgehog gene
A
produced at base of limbs in zone of polarizing activity. Involved in patterning along anterior-posterior axis. Involved in CNS development; mutation can cause holoprosencephaly
2
Q
Wnt-7 gene
A
produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb). Necessary for proper organization along dorsal ventral axis.
3
Q
FGF gene
A
produce at apical ectodermal ridge. Stimulates mitosis of underlying mesoderm, providing lengthening of limbs.
4
Q
Hox genes
A
Involved in segmental organization of embryo in craniocaudal direction. Code for transcription factors. Hox mutations causes appendages in wrong locations
5
Q
Within 1 week of fetal development
A
hCG secretion begins around the time of implantation of blastocyst (it sticks at day 6)
6
Q
Within week 2 of fetal development
A
bilaminar disc (epiblast, hypoblast. 2 weeks=2 layers
7
Q
Within week 3 of fetal development
A
trilaminar disc. 3 weeks=3layers. Gastrulation. Primitive streak, notochord, mesoderm and its organization, and neural plate begin to form.
8
Q
weeks 3-8 (embryonic period) of fetal development
A
Neural tube formed by neuroectoderm and close by week 4. Organogensis. Extremely susceptible to teratogens.
9
Q
week 4 of fetal development
A
heart begins to beat. upper and lower limb buds begin to form. 4 weeks=4 limbs.
10
Q
week 6 of fetal development
A
fetal cardiac visible by transvaginal ultrasound.
11
Q
week 10 of fetal development
A
genitalia have male/ female characteristics.
12
Q
gastrulation
A
process that forms the trilaminar embryonic disc. Establishes the ectroderm, mesoderm, and endoderm germ layers. Starts with the epiblast invaginating to form the primitive streak.
13
Q
female genital embryology
A
Default development. Mesonephric duct degenerates and paramesonephric duct develops.
14
Q
male genital embryology
A
SRY gene on Y chromosome produces testis determining factor leading to testes development. Sertoli cells secrete Mullerian inhibitory factor (MIF) that suppresses developent of paramesonephric ducts. Leydig cells secrete androgens that stimulate development of mesonephric ducts.
15
Q
Paramesonephric duct
A
mullerian duct. develops into female internal structures– fallopian tubes, uterus, upper portion of vagina (lower portion from urogenital sinus).
16
Q
Mullerian agenesis
A
may present as primary amenorrhea (due to a lack of uterine development) in females with fully developed secondary sexual characteristics (functional ovaries).
17
Q
Mesonephric duct
A
develops into male internal structures (except prostate)– seminal vesicles, Epididymis, Ejaculatory duct, Ductus deferens (SEED). In females, remnant of mesonephric duct becomes Gartner duct.
18
Q
Mullerian inhibitory factor deficiency
A
leads to both male and female internal genitalia and male external genitalia. This can also occur due to lack of Sertoli cells.
19
Q
5 alpha reductase deficiency
A
inability to convert testosterone into DHT causing male internal genitalia, ambiguous external genitalia until puberty (when increase testosterone levels cause masculinization.
20
Q
Septate uterus
A
Common anomaly. Incomplete resorption of septum. Decrease fertility. Treat with septoplasty.
21
Q
Bicornuate uterus
A
incomplete fusion of mullerian ducts. Increase risk of complicated pregnancy.
22
Q
Uterus didelphys
A
complete failure of fusion leads to double uterus, vagina, and cervix. Pregnancy possible.
23
Q
Genital tubercle
A
becomes glans penis, corpus cavernosum, and songiosum in males and glans clitoris, vestibular bulbs, and greater vestibular glands (of bartholin) in women.
24
Q
Urogenital sinus
A
becomes bulbourethral glands (of Cowper), prostate gland, and ventral shaft of penis (penile urethra) in males and greater vestibular glands (of Bartholin), urethral and paraurethral glands (of Skene), and labia minora in women.
25
labioscrotal swelling
becomes scrotum in males and labia majora in women.
26
hypospadias
abnormal opening of penile urethra on ventral surface of penis due to failure of urethral folds to fuse. Hypospadias is more common than epispadias. Associated with inguinal hernia and cryptorchidism. Hypo is below.
27
Epispadias
Abnormal opening of penile urethra on dorsal surface of penis due to faulty positioning of genital tubercle. Exstrophy of the bladder is associated with epispadias. When you have epispadias, you hit your eye when you pee.
28
gubernaculum
band of fibrous tissue. anchors testes within scrotum in males. ovarian ligament and round ligament of uterus in women.
29
venous gonadal drainage
left ovary/testis drains into left gonadal vein than into left renal vein than into IVC. Left gonadal vein takes the longest way. Because the left spermatic vein enters the left vein at a 90 degree angle, flow is less laminar on the left than on right causing left venous pressure to be greater than the right venous pressure. This is why varicocele is more common on the left.
30
Lymphatic drainage of ovaries/ testes
drains to para-aortic lymph nodes
31
Lymphatic drainage of distal vagina/vulva/scrotum
drains to superficial inguinal nodes
32
Lymphatic drainage of proximal vagina/uterus
drains to obturator, external iliac and hypogastric nodes
33
infundibulopelvic ligament
also called suspensory ligament of the ovary. Connects ovaries to lateral pelvic wall. Contains ovarian vessels. Ligate vessels during oophorectomy to avoid bleeding. Ureter courses retroperitoneally, close to gonadal vessels. There is a risk of injury during ligation ovarian vessels.
34
cardinal ligament
connects cervix to side wall of pelvis. Contains the uterine vessels. Ureter at risk of injury during ligation of uterine vessels in hysterectomy
35
round ligament of the uterus
connects uterine fundus to labia majora. Derivative of gubernaculum. Travels through round inguinal canal; above the artery of Sampson (the anastomosis of the uterine artery and ovarian artery).
36
broad ligament
connects uterus, fallopain tubes, and ovaries to pelvic side wall. Contains ovaries, fallopian tubes, round ligaments of uterus. Mesosalpinx, mesometrium, and mesovarium comprise the broad ligament.
37
Ovarian ligament
connects medial pole of ovary to lateral uterus. Derivative of gubernaculum. Ovarian ligament latches to lateral uterus.
38
histology of the vagina
stratified squamous epithelium, nonkeratinized
39
histology of the ectocervix
stratified squamous epithelium, nonkeratinized
40
histology of the transformation zone
squamocolumnar junction (most common area for cervical cancer)
41
histology of the endocervix
simple columnar epithelium
42
histology of the uterus
simple columnar epithelium with long tubular glands in follicular phase, coiled glands in luteal phase.
43
histology of the fallopian tube
simple columnar epithelium ciliated
44
histology of the ovary, outer surface
simple cuboidal epithelium (germinal epithelium covering surface of ovary)
45
female sexual response cycle
most commonly described as phase of excitement (uterus elevates, vaginal lubrication), plateau (expansion of inner vagina), orgasm (contraction of uterus), resolution; mediated by autonomic nervous system. Also causes tachycardia and skin flushing.
46
pathway of sperm during ejaculation
SEVENUP: Seminiferous tubules, Epididymis, Vas deferens, Ejaculatory ducts, (nothing), Urethra, Penis
47
Urethral injury
suspect if blood seen at urethral meatus. posterior urethra- membranous urethra prone to injury from pelvic fracture; bulbar urethra susceptible to blunt force. Injury can cause urine to leak into retropubic space. Anterior urethra- penile urethra at risk of damage due to perineal straddle injury. Can cause urine to leak beneath deep fascia of Buck. If fascia is torn, urine escapes into superficial perineal space.
48
autonomic innervation of the male sexual response
Erection is under parasympathetic nervous system (pelvic nerve): NO causes increase of cGMP, causing smooth muscle relaxation leading to vasodilation, which is proerectile. Norepinephrine causes an increase in intracellular Ca, causing vasoconstriction, which is antierectile. Emission is under control of sympathtic nervous (hypogastric nerve). Ejaculation is under the control of visceral and somatic nervous system (the pudendal nerve). Point and Shoot. PDE-5 inhibitors (eg sildenafil) decreases cGMP breakdown.
49
Spermatogonia (germ cells)
maintain germ pool and produce primary spermatocytes. They line seminiferous tubules.
50
Sertoli cells
Secrete inhibin, which inhibits FSH. Secrete androgen binding protein, which maintain local levels of tostoterone. Tight junctions between adjacent sertoli cells form blood testis barrier, which isolates gametes from autoimmune attack. Support and nourish developing spermatozoa. Regulate spermatogenesis. Produce MIF. Temperature sensitive; with an increase of temperature, sperm production decreases and inhibin decreases. An increase of temperature is seen in varicocele cryptochidism. They line the seminiferous tubules, convert testosterone and androstenedione to estrogens via aromatase. Sertoli cells support sperm synthesis. Homolog of female granulosa cells.
51
Leydig cells
Endocrine cells. Secrete testosterone in the presence of LH; testosterone production unaffected by temperature. Located in the interstitum. Homolog of female theca interna cells.
52
Estrogen
There are three types: ovary (17beta-estradiol), placenta (estriol), adipose tissue (estrone via aromatization). Potency: estradiol>estrone>estriol. It causes the development of genitalia and breast, female fat distribution. It also regulates the growth of follicle, endometrial proliferation, and increases myometrial excitability. It also leads to upregulation of estrogen, LH, and progesterone receptors; feedback inhibition of FSH and LH, then LH surge; stimulation of prolactin secretion. It also increases transport proteins, SHBG; increases HDL, and decreases LDL. In pregnancy, there is a 50 fold increase in estradiol and estrone and a 1000 fold increase in estriol (an indicator of fetal well-being). Estrogen receptors are expressed in the cytoplasm; it translocates to nucleus when bound by estrogen.
53
aromatase
converts androgens to estrogens in granulosa cells in response to FSH.
54
Desmolase
converts cholesterol to androgens in theca interna cells in response to LH
55
progesterone
Sources include corpus luteum, placenta, adrenal cortex, testes. It stimulates secretions from the endometrial glandular secretions and spiral artery development. It also maintains of pregnancy, decreases myometrial excitability. It also triggers the production of thick cervical mucus, which inhibits sperm entry into uterus. It also increases body temperature, inhibits gonadotropins (LH, FSH), causes uterine smooth muscle relaxation (preventing contractions), decreases estrogen receptor expression, and prevents endometrial hyperplasia. A fall in progesterone after delivery disinhibits prolactin leading to lactation. An increase in progesterone is indicative of ovulation. Progesterone is pro-gestation. Prolactin is pro-lactation.
56
Tanner stages of sexual development
Tanner stage is assigned independently to genitalia, pubic hair, and breast. I. childhood. II. pubic hair appears (pubarche); breast buds form (thelarche). III. pubic hair darkens and becomes curly; penis size/length increases; breasts enlarge. IV. penis width increases, darker scrotal skin, development of glans; raised areolae. V. adult; areolae are no longer raised.
57
Menstrual cycle
Follicular phase can vary in length. Luteal phase is 14 days. Ovulation day plus 14 days= menstruation. Follicular growth is fastest during 2nd week of proliferative phase. Estrogen stimulates endometrial proliferation. Progesterone maintains endometrium to support implantation. A decrease in progesterone leading to a decrease in fertility. An increase in estrogen causes an LH surge, causing ovulation, which causes progesterone to be released from the corpus luteum. When progesterone levels fall, menstruation begins via apoptosis of endometrial cells.
58
metrorrhagia
frequent or irregular menstruation.
59
menorrhagia
heavy menstrual bleeding; more than 80 ml blood loss or greater than 7 days of menses
60
menometrorrhagia
heavy irregular menstruation.
61
Oogenesis
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. Meiosis II is arrested in metaphase II until fertilization. If fertilization does not occur within 1 day, the secondary oocyte degenerates.
62
ovulation
with an increase in estrogen, there is an increase of GnRH receptors on anterior pituitary. Estrogen surge then stimulates LH release, causing ovulation (rupture of follicle). There is also an increase in temperature, which is progesterone induced.
63
Mittelschmerz
transient mid-cycle ovulatory pain; classically associated with peritoneal irritation (eg follicular swelling/rupture, fallopian tube contraction). Can mimic appendicitis.
64
Pregnancy
Fertilization most commonly occurs in upper end of fallopian tube (the ampulla). Occurs within 1 day of ovulation. Implantation within the wall of the uterus occurs 6 days after fertilization. Syncytiotrophoblasts secrete hCG, which is detectable in blood 1 week after conception and on home test in urine 2 weeks after conception.
65
Lactation
After labor, the decrease in progesterone and estrogen disinhibits lactation. Suckling is required to maintain milk production, since an increase in nerve stimulation leads to an increase in oxytocin and prolactin. Prolactin induces and maintains lactation and decreases reproductive function. Oxytocin assists in milk letdown; also promotes uterine contractions. Breast milk is the ideal nutrition for infants under 6 months of age. contains Ig (passive immunity; IgA), macrophages, lymphocytes. Breast milk reduces infant infections and is associated a decrease risk for child to develop asthma, allergies, diabetes mellitus, and obesity. Exclusively breastfed infants require vitamin D supplementation. Breastfeeding decreases maternal risk of break and ovarian cancer and facilitates mother child bonding.
66
hCG
released from syncytiotrophoblast of placenta. It maintains corpus luteum (and thus progesterone) for first 8-10 weeks of pregnancy by acting like LH (otherwise no luteal cell stimulation, which leads to abortion). After 8-10 weeks, placenta synthesizes its own estriol and progesterone and corpus luteum degenerates. Used to detect pregnancy because it appears early in urine. It has an identical alpha subunit as LH, FSH, TSH. Beta subunit is unique (pregnancy test detect beta subunit). hCG is increased in multiple gestations, hydatidiform moles, choriocarcinomas, and Down syndrome. hCG is decreased in ectopic/failing pregnancy, Edward syndrome, and Patau syndrome.
67
menopause
A decrease in estrogen production due to age linked decline in number of ovarian follicles. Average age at onset is 51 years (earlier in smokers). Usually preceded by 4-5 years of abnormal menstrual cycles. Source of estrogen (estrone) after menopause becomes peripheral conversion of androgens, an increase in androgens leads to hirsutism. A large increase in FSH is specific for menopause (loss of negative feedback on FSH due to a decrease in estrogen). Hormonal changes include: a decrease in estrogen, a large increase in FSH, an increase in LH (no surge), and an increase in GnRH. Menopause causes hot flashes, atrophy of the vagina, osteoporosis, coronary artery disease, and sleep disturbances. Menopause before age 40 can indicate premature ovarian failure.
68
spermatogenesis
Spermatogenesis begins at puberty with spermatogonia. Full development takes 2 months. Occurs in seminiferous tubules. produces spermatids that undergo spemiogenesis (loss of cytoplasmic contents, gain of acrosomal cap) to form mature spermatozoon.
69
gonium
the germ cell during the phase marked by mitosis.
70
androgens
testosterone, dihydrotestosterone (DHT), androstenedione. DHT and testosterone come from the testis, androstenedione comes from the adrenal glands. Potency: DHT>testosterone>androstenedione. In the male, androgens are converted to estrogen by cytochrome P-450 aromatase (primarily in adipose tissue and testis).
71
testosterone
Causes differentiation of epididymis, vas deferens, seminal vesicles (genitalia, except prostate). It also triggers a growth spurt: penis, seminal vesicles, sperm, muscle, RBCs; deepening of voice; closing of epiphyseal plates (via estrogen converted from testosterone); libido. Exogenous testosterone inhibits the hypothalamic- pituitary- gonadal axis, which decreases intratesticular testosterone leading to decrease testicular size and azoospermia.
72
DHT
Early on, it causes differentiation of penis, scrotum, prostate. Later, is causes prostate growth, balding, sebaceous gland activity.
73
finasteride
inhibits 5 alpha reductase, which converts testosterone to DHT.
74
Klinefelter Syndrome
XXY, 1:850. Testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution. May present with developmental delay. Presence of inactivated X chromosome (Barr body). Common cause of hypogonadism seen in infertility work up. Dysgenesis of seminiferous tubules causes a decrease in inhibin, leading to an increase in FSH. Abnormal Leydig cell function leads to a decrease in testosterone, causing an increase in LH, which leads to an increase in estrogen.
75
Turner syndrome
45, XO. Short stature, ovrian dysgenesis (streak ovary), shield chest, bicupsid aortic valve, preductal coarctation (femoral is less than brachial pulse), lymphatic defects (results in webbed neck or cystic hygroma; lymphedema in feet and hands), horseshoe kidney. Most common cause of amenorrhea. No barr body. Decrease estrogen leads to increase in LH, FSH. Can result from mitotic or meiotic error. Can be complete monosomy or mosaicism. Pregnancy is possible in some cases (oocyte donation, exogenous estrdiol 17beta and progesterone).
76
Double Y males
(XYY), phenotypically normal (usually undiagnosed), very tall. Random nondisjunction event (paternal meiosis II); noninherited; normal fertility. May be associated with sever acne, learning disability, autism spectrum disorder.
77
ovotesticular disorder of sex development.
also called true hermaphroditism. both ovarian and testicular tissue is present; ambiguous genitalia. 46, XX or 47 XXY.
78
female pseudohermaphrodite (XX)
ovaries are present, but external genitalia are virilized or ambiguous. Due to excessive inappropriate exposure to androgenic steroids during early gestation (eg congenital adrenal hyperplasia or exogenous administration of androgens during pregnancy).
79
Male pseudohermaphrodite (XY)
testes present, but external genitalia are female or ambiguous. Most common form is androgen insensitivity syndrome, which is due to a defective androgen receptor.
80
aromatase deficiency
inability to synthesize estrogen from androgens. Masculization of female (46, XX) infants (ambiguous genitalia), increase in serum testosterone and androstenedione. can present with maternal virilization during pregnancy (fetal androgens cross the placenta).
81
androgen insensitivity syndrome
46 (XX). Defect in androgen receptor resulting in normal appearing female; female external genitalia with scant sexual hair, rudimentary vagina; uterus and fallopian absent. Patients develop testes (often found in the labia majora; surgically removed to prevent malignancy). Increase in testosterone, estrogen, LH (vs. sex chromosome disorders).
82
5 alpha reductase deficiency
Autosomal recessive; sex limited to genetic males (46, XY). Inability to convert testosterone to DHT. Ambiguous genitalia until puberty, when an increase in testosterone causes masculinization/ increase growth of external genitalia. Testosterone/ estrogen levels are normal; LH is normal or increases. Internal genitalia are normal.
83
Kallmann Syndrome
failure to complete puberty; a form of hypogonadotropic hypogonadism. Defective migration of GnRH cells and formation of olfactory bulb; an increase of synthesis of GnRH in the hypothalamus; anosmia; a decrease of GnRH, FSH, LH, testosterone. Infertility (low sperm count in males; amenorrhea in females).
84
Hydatidiform mole
cystic swelling of chorionic villi and proliferation of chorionic epithelium (only trophoblast). Associated with theca-lutein cysts, hyperemesis gravidarum, hyperthyroidism. Treatment is dilation and curettage and methostrexate. Monitor beta-hCG. can be complete or partial
85
complete mole
karyotype is either 46 (XX); 46 (XY). hCG is extremely elevated. Uterine size is increased. About 2% convert to choriocarcinoma. Commonly composed of enucleated egg and single sperm (subsequently duplicates paternal DNA). 15-20% are complicated by malignant trophoblastic disease. No fetal parts. Symptoms include first trimester bleeding, enlarged uterus, hyperemesis, pre-eclampsia before 20 weeks, hyperthyroidism. Appears as a honeycombed uterus or clusters of grapes; snowstorm on ultrasound.
86
partial mole
Karyotype is either 69 (XXX), 69 (XXY), 69 (XYY). hCG is increased but not as much as with a complete mole. No enlargement of the uterus. Rarely converts to choriocarcinoma. Contains fetal parts, which can be seen on imaging. (PARTial= fetal PARTs) Composed of two sperms and 1 egg. Low risk of malignancy (less than 5%). Symptoms include vaginal bleeding, abdominal pain.
87
Gestational hypertension (pregnancy- induced hypertension)
BP is greater than 140/90 mm Hg after 20th week of gestation. No pre-existing hypertension. No proteinuria or end organ damage. Treatment includes antihypertensives (alpha-methyldopa, labetalol, hydralazine, nifedipine), deliver at 37-39 weeks.
88
Preeclampsia
new onset hypertension with either proteinuria or end organ dysfuntion after 20 week of gestation (less than 20 weeks suggests molar pregnancy). May proceed to eclampsia (seizures) and/or HELLP syndrome. Caused by abnormal placental spiral arteries, which causes endothelial dysfunction, vasoconstriction, and ischemia. Incidence increases in patients with pre-existing hypertension, diabetes, chronic renal disease, autoimmune disorders.
89
Preeclampsia complications
placental abruption, coagulopathy, renal failure, uteroplacental insufficiency, eclampsia.
90
Preeclampsia treatment
antihypertensives, IV magnesium sulfate (to prevent seizure); definitive is delivery of fetus.
91
Eclampsia
preeclampsia plus maternal seizures. Maternal death due to stroke, intracranial hemorrhage or ARDS. Treatment include IV magnesium sulfate, antihypertensives, immediate delivery.
92
HELLP syndrome
Hemolysis, Elevated Liver enzymes, Low Platelets. A manifestation of severe preeclampsia. Blood smear shows schistocytes. Can lead to hepatic subcapsular hematomas, which can rupture, leading to severe hypotension. Treatment is immediate delivery.
93
placental abruption (abruptio placentae)
premature seperation (partial or complete) of placenta from uterine wall before delivery of infant. Risk factors include trauma (eg motor vehicle accident), smoking, hypertension, preeclampsia, cocaine abuse. Presentation is abrupt, painful bleeding (concealed or apparent) in third trimester; possible DIC, maternal shock, fetal distress. Life threatening for mother and fetus.
94
placenta accreta/ increta/ percreta
defective decidual layer leads to abnormal attachment and separation after delivery. Risk factors include prior C-section, inflammation, placenta previa. Three types distinguishable by depth of penetration. They are often dectable on ultrasound prior to delivery. No separation of placenta after delivery leads to postpartum bleeding (can cause Sheehan syndrome)
95
placenta accreta
placenta attaches to myometrium without penetrating it; most common type.
96
placenta increta
placenta penetrates into myometrium
97
placenta percreta
placenta penetrates (perforates) through myometrium and into uterine serosa (invades entire uterine wall); can result in placental attachment to rectum or bladder.
98
Placenta previa
Attachment of placenta to lower uterine segment over (or less than 2 cm from) internal cervical os. Risk factors include multiparity, prior C-section. Associated with painless third-trimester bleeding.
99
Vasa previa
fetal vessels run over, or in close proximity to, cervical ox. May result in vessel rupture, exsanguination, fetal death. Presents with triad of membrane rupture, painless vaginal bleeding, fetal bradycardia (less than 110 beats/min). Emergency C-section usually indicated. Frequently associated with velamentous umbilical cord insertion (cord inserts in chorioamniotic membrane rather than placenta, which causes fetal vessels to travel to placenta unprotected by Wharton jelly)
100
retained placental tissue
may cause postpartum hemorrhage, increase risk of infection
101
Ectopic pregnancy
most often in the ampulla of fallopian tube. Suspect with history of amenorrhea, lower than expected rise in hCG based on dates, and sudden lower abdominal pain; cofirm with ultrasound. Often clincally mistaken for appendicitis. Pain with or without bleeding. Risk factors include history of infertility, salpingitis (PID), ruptured appendix, prior tubal surgery.
102
Polyhydramnios
too much (greater than 1.5-2 L) amniotic fluid; associated with fetal malformations (eg esophageal. duodenal atresia, anencephaly; both result in inability to swallow amniotic fluid), maternal diabetes, fetal anemia, multiple gestations.
103
Oligohydramnios
too little (less than .5L) amniotic fluid; associated with placental insufficiency, bilateral renal agenesis, posterior urethral valves (an obstructing membrane in the posterior male urethra as a result of abnormal in utero development, most common cause of bladder outlet obstruction in males) and resultant inability to excrete urine. Any profound oligohydramnios can cause Potter sequence.
104
Gynecologic tumor incidence (US)
endometrial is most common, than ovarian, than cervical; cervical cancer is more common worldwide due to lack of screening or HPV vaccination.
105
Gynecologic tumor prognosis
worst prognosis is ovarian cancer, than cervical, than endometrial.
106
vaginal squamous cell carcinoma (SCC)
usually secondary to cervical SCC; primary vaginal carcinomas are rare.
107
vaginal clear cell adenocarcinoma
affects women who had exposure to diethylstilbestrol (DES, a synthetic form of the female hormone estrogen in utero, discontinued use in 1971) in utero.
108
vaginal sarcoma botryoides (rhabdomyosarcoma variant)
affects girls less than 4 years old; spindle- shaped cells; desmin (a muscle-specific, type III intermediate filament) positive. Presents with clear, grape-like, polypoid mass emerging from vagina
109
Dysplasia and carcinoma in situ cervical pathology
Disordered epithelia growth; begins at basal layer of squamocolumnar junction (a transitional area between squamous epithelium of the vagina and the columnar epithelium of the endocervix) and extends outwards. Classified as CIN 1, CIN 2, or CIN 3 (severe dysplasia or carcinoma in situ), depending on extent of dysplasia. Associated with HPV 16 and HPV 18, which produce both the E6 gene product (inhibits p53 suppressor gene) and E7 gene (inhibits RB suppressor gene). May progress slowly to invasive carcinoma if left untreated. Typically asymptomatic (detected with Pap smear) or presents as abnormal vaginal bleeding (often postcoital). Risk factors include having multiple sexual partners (#1), smoking, starting sexual intercourse at young age, HIV infection.
110
Invasive carcinoma cervical pathology
often squamous cell carcinoma. Pap smear can catch cervical dysplasia (koilocytes, have wrinkled raisinoid nuclei, some of which have clearing or a perinuclear halo) before it progresses to invasive carcinoma. Diagnose via colposcopy and biopsy. Lateral invasion can block ureters, which can cause renal failure.
111
premature ovarian failure
premature atresia of ovarian follicles in women of reporductive age. Patients present with signs of menopause after puberty but before age 40. there is decreased estrogen, increase LH, and increase FSH.
112
most common causes of anoculation
pregnancy, polycystic ovarian syndrome, obesity, HPO axis abnormalities, premature ovarian failure, hyperprolactinemia, thyroid disorders, easting disorders, competitive athletics, Cushing syndrome, adrenal insufficiency.
113
Polycystic ovarian syndrome (Stein-Leventhal syndrome)
Hyperinsulinemia and/or insulin resistance hypothesized to alter hypothalamic hormonal feedback response causing an increase in the LH:FSH ratio, increase androgens released from theca interna cells, a decrease in the rate of follicular maturation, leading to unruptured follicles (cysts) with anovulation. Common cause of subfertility in women. Enlarged bilateral cystic ovaries; presents with amenorrhea/oligomenorrhe, hirsutism, acne, subfertility. Associated with obsesity. There is an increase risk of endometrial cancer secondary to unopposed estrogen from repeated anovulatory cycles. Treatment is weight reduction, OCPs, clomiphene citrate, ketoconazole, spironolactone.
114
Follicular cyst
distention of unruptured graafian follicle (a fluid-filled structure in the mammalian ovary within which an ovum develops before ovulation). May be associated with hyperestrogenism, endometrial hyperplasia. Most common ovarian mass in young women.
115
theca leutein cyst
often bilateral/ multiple. Due to gonadotropic stimulation. Associated with choriocarcinoma and hydatidiform moles.
116
ovarian neoplasms
most common adnexal (structures closely related structurally and functionally to the uterus such as the ovaries, fallopian tubes, or any of the surrounding connective tissue) mass in women over 55 years old. Can benign or malignant. Arise from surface epithelium, germ cells, or sex cord stromal tissue. Majority of malignant tumors are epithelial (serous cystadenocarcinoma most common). Risk increases with advanced age, infertility, endometriosis, PCOS, genetic predisposition (BRCA-1 or BRCA-2 mutations, hereditary nonpolyposis colorectal cancer (HNPCC), strong family history). Risk decreases with previous pregnancy, history of breastfeeding, OCPs, tubal ligation. Presents with adnexal mass, abdominal distention, bowel obstruction, pleural effusion. Diagnose surgically. Monitor progression by measuring CA 125 levels (not good for screening).
117
serous cystadenoma
benign ovarian neoplasm. Most common ovarian neoplasm. Lined with fallopian tube like epithelium. Often bilateral.
118
mucinous cystadenoma
benign ovarian neoplasm. multiloculated, large. lined by mucus secreting epithelium.
119
endometrioma
benign ovarian neoplasm. endometriosis (ectopic endometrial tissue) within ovary with cyst formation. presents with pelvic pain, dysmenorrhea, dyspareunia; symptoms may vary with menstrual cycle. Chocolate cyst is an endometrioma filled with dark, reddish-brown blood. Complex mass on ultrasound.
120
mature cystic teratoma (dermoid cyst)
benign ovarian neoplasm. germ cell tumor, most common ovarian tumor in women 20-30 years old. cystic mass containing elements from all 3 germ layers (eg teeth, hair, sebum). Can present with pain secondary to ovarian enlargement or torsion. Can also contain functional thyroid tissue and present as hyperthyroidism (struma ovarii).
121
Brenner tumor
benign ovarian neoplasm. looks like Bladder. Solid tumor that is pale yellow tan and appears encapsulated. Coffee Bean nuclei on H and E stain.
122
fibromas
benign ovarian neoplasm. bundles of spindle shaped fibroblasts. releated to Meigs syndrome, a triad of ovarian fibroma, ascites, and hydrothorax.
123
Meigs syndrome
a triad of ovarian fibroma, ascites, and hydrothorax. Pulling sensation in groin.
124
thecoma
benign ovarian neoplasm. like granulosa cell tumors, may produce estrogen. Usually presents as abnormal uterine bleeding in a postmenopausal women.
125
immature teratoma
Malignant ovarian neoplasm. aggressive, contains fetal tissue, neuroectoderm. Immature teratoma is most typically represented by immature/ embryonic like neural tissue. Mature teratoma are more likely to contain thyroid tissue.
126
granulosa cell tumor
Malignant ovarian neoplasm. Most common malignant stromal tumor. predominatly women in their 50s. often produces estrogen and/or progesterone and presents with abnormal uterine bleeding, sexual precocity (appearance of secondary sexual characteristics before the lower limit of the normal age for pubertal onset), breast tenderness. Histology shows Call-Exner bodies (granulosa cells arranged haphazardly around collections of eosinophilic fluid, resembling primordial follicles).
127
serous cystadenocarcinoma
Malignant ovarian neoplasm. most common ovarian neoplasm, frequently bilateral. psammoma bodies.
128
Mucinous cystadenocarcinoma
Malignant ovarian neoplasm. Causes pseudomyxoma peritonei, which is an intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor.
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Dysgerminoma
Malignant ovarian neoplasm. Most common in adolescents. Equivalent to male seminoma but rarer. 1% of all ovarian tumors; 30% of germ cell tumors. Sheets of uniform fried egg cells. hCG, LDH (lactate dehydrogenase) are tumor markers.
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Choriocarcinoma
Malignant ovarian neoplasm. Rare; can develop during or after pregnancy in mother or baby. Malignancy of trophoblastic tissue (cytotrophoblasts, syncytiotrophoblasts); no chorionic villi present. Increase frequency of bilateral/ multiple theca lutein cysts. Presents with abnormal increase of beta-hCG, shortness of breath, hemoptysis. Hematogenous spread to lungs. Very responsive to chemotherapy.
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Yolk sac (endodermal sinus) tumor
Malignant neoplasm. Aggressive, in ovaries or testes and sacrococcygeal area in young children. Most common tumor in male infants. Yellow, friable (hemorrhagic), solid mass. 50% have schiller duval bodies (resemble glomeruli). AFP (Alpha-fetoprotein) is a tumor marker
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krukenberg tumor
Malignant ovarian neoplasm. GI malignancy that metastasizes to ovaries, causing mucin secreting signet cell adenocarcinoma.
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endometrial polyp
well-circumscribed collection of endometrial tissue within uterine wall. May contain smooth muscle cells. Can extend into endometrial cavity in the form of a polyp.
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Endometrial Leiomyoma (fibroid)
most common tumor in females. Often presents with multiple discrete tumors. Increase incidence in blacks. Benign smooth muscle tumor; malignant transformation is rare. Estrogen sensitive, therefore tumor size increases with pregnancy and decreases with menopause. Peak occurrence in 20-40 year olds. May be asymptomatic, cause abnormal uterine bleeding or result in miscarriage. Severe bleeding may lead to iron deficiency anemia. Usually does not progress to leiomyosarcoma. Whorled pattern of smooth muscle bundles with well demarcated borders.
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Adenomyosis
Extension of endometrial tissue (glandular) into uterine myometrium. Caused by hyperplasia of basal layer of endometrium. Presents with dysmenorrhea, menorrhagia, uniformly enlarged soft, globular uterus. Treatment includes GnRH agonists, hysterectomy.
136
Endometriosis
Non-neoplastic endometrial glands/stroma outside endometrial cavity. Can be found anywhere; most common sites are ovary (frequently bilateral), pelvis, peritoneum. In ovary, appears as endometrioma (blood-filled chocolate cyst). May be due to retrograde flow, metaplastic transformation of multipotent cells, transportation of endometrial tissue via lymphatic system. Characterized by cyclic pelvic pain, bleeding, dysmenorrhea, dyspareunia, dyschezia (pain with defecation), infertility; normal sized uterus. Treatment includes NSAIDs, OCPs, progestins, GnRH agonists, danazol, laparoscopic removal.
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Endometritis
inflammation of endometrium associated with retained products of conception following delivery, miscarriage, abortion, or with foreign bodies (eg IUD). Retained material in uterus promotes infection by bacterial flora from vagina or intestinal tract. Treatment includes gentamicin and clindamycin with or without ampicillin.
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Endometrial hyperplasia
Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation. There is an increase risk for endometrial carcinoma. Presents as postmenopausal vaginal bleeding. Risk factors include anovulatory cycles, hormone replacement therapy, polycystic ovarian syndrome, granulosa cell tumor.
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Endometrial carcinoma
Most common gynecologic malignancy. Peak occurrence in 55-65 year old. Presents with vaginal bleeding. Typically preceded by endometrial hyperplasia. Risk factors include prolonged use of estrogen without progestins, obesity, diabetes, hypertension, nulliparity, late menopause, Lynch syndrome.
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Fibroadenoma
Benign breast tumors. small, mobile, firm mass with sharp edges. Most common tumor in those under the age of 35. There is an increase in size and tenderness with an increase in estrogen (eg pregnancy, prior to menstruation). Not a precursor to breast cancer.
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Intraductal papilloma
Benign breast tumors. Small tumor that grows in lactiferous ducts. Typically beneath areola. Serous or bloody nipple discharge. Slight (1.5-2x) increase in risk for carcinoma.
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Phyllodes tumor
Benign breast tumors. Large bulky mass of connective tissue and cysts. Leaf like projections. Most common in 5th decade. Some may become malignant.
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Proliferative breast disease
most common cause of breast lumps from age 25 to menopause. Present with premenstrual breast pain and multiple lesions, often bilateral. Fluctuation in size of mass. Usually does not indicate increased risk of carcinoma. Histologic types: fibrosis, cystic, sclerosing adenosis, epithelial hyperplasia.
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Fibrotic proliferative breast disease
hyperplasia of breast stroma.
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cystic proliferative breast disease
fluid filled, blue dome. Ductal dilation.
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sclerosing adenosis proliferative breast disease
an increase acini and intralobular fibrosis. Associated with calcifications. Often confused with cancer. An increase in (1.5-2x) of developing cancer.
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epithelial hyperplasia proliferative breast disease
increase in number of epithelial cell layers in terminal duct lobule. An increase in risk of carcinoma with atypical cells. Occurs in women over the age of 30.
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Lactational mastitis
During breastfeeding, there is an increase of bacterial infection through cracks in the nipple; S aureus is most common pathogen. Treat with dicloxacillin and continued breastfeeding.
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Fat necrosis of the breast
benign, usually painless lumps, forms as a result of injury to breast tissue. Abnormal calcification on mammography; biopsy shows necrotic fat, giant cells. Up to 50% of patients may not report trauma.
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Gynecomastia
Breast enlargement in males. Results from hyperestrogenism (cirrhosis, testicular tumor, puberty, old age), Klinefelter syndrome, drugs (Spironolactone, Digoxin, Cimetidine, Alcohol, Ketoconazole). Some Drugs Create Awesome Knockers. Physiologic (not pathologic) at birth, puberty, old age.
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Malignant breast tumors
commonly postmenopausal. Usually arise from terminalduct lobular unit. Overexpression of estrogen/progesterone receptors or c-erbB2 (HER-2, an EGF receptor) is common; triple negative (estrogen receptor neg, progesterone receptor neg, Her2/Neu neg) more aggressive; type affects therapy and prognosis. Axillary lymph node involvement indicating metastasis is the single most important prognostic factor. Most often located in upper outer quadrant of breast. Risk factors include increase estrogen exposure, increase in total number of menstrual cycles, older age at 1st live birth, obesity (an increase in estrogen exposure as adipose tissue converts androstenedione to estrone), BRCA1 and BRCA2 gene mutations, African American ethnicity (an increase risk for triple negative breast cancer).
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Ductal carcinoma in situ (DCIS)
Malignant. Fills ductal lumen. Arises from ductal atypia. Often seen early as microcalcifications on mammography. Early malignancy without basement membrane penetration.
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Comedocarcinoma
Malignant. ductal, central necrosis. Subtype of DCIS.
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Paget disease
results from underlying DCIS or invasive breast cancer. Eczematous patches on nipple. Paget cells= large cells in epidermis with clear halo. Extramammary Paget disease seen on vulva does not suggest underlying malignancy.
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Invasive ductal breast cancer
malignant, firm, fibrous, rock hard mass with sharp margins and small, glandular duck like cells. Grossly, there is satellite infiltration. Worst and most invasive. Most common of all breast cancers.
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invasive lobular breast cancer
Malignant. Orderly row of cells (indian file), due to decrease E-cadherin expression. Often bilateral with multiple lesions in the same location.
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Medullary breast cancer
Malignant. Fleshy, cellular, lymphocytic infiltrate. Good prognosis.
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Inflammatory breast cancer
Dermal lymphatic invasion by breast carcinoma. Peau d'orange (breast skin resembles orange peel), neoplastic cells block lymphatic drainage. 50% survival over 5 years. Often mistaken for mastitis or Paget disease.
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Peyronie disease
Abnormal curvature of penis due to fibrous plaque within tunica albuginea. Associated with erectile dysfunction. Can cause pain, anxiety. Consider surgical repair once curvature stabilizes. Distinct from penile fracture (rupture of corpora cavernosa due to forced bending).
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Priapism
Painful sustained erection lasting greater than 4 hours. Associated with trauma, sickle cell disease (sickled RBC's get trapped in vascular channels), medications (eg sildenafil, trazodone). Treat immediately with corporal aspiration, intracavernosal phenylephrine, or surgical decompression to prevent ischemia.
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Penile squamous cell carcinoma
more common is Asia, Africa, South America. Precursor in situ lesions: Bowen disease (in penile shaft, presents as leukoplakia), erthroplasia of Queyrat (cancer of glans, presents as erythroplakia), Bowenoid papulosis (carcinoma in situ of unclear malignant potential, presenting as reddish papules). Associated with HPV, lack of circumcision.
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Cryptochidism
Undescended testis (one or both); impaired spermatogenesis (since sperm develop best at temperatures less than 37 degrees Celsius); can have normal testosterone levels (leydig cells are unaffected by temperature); associated with increase risk of germ cell tumors. Prematurity increases risk of cryptorchidism. There is a decrease in inhibin, an increase FSH, an increase in LH; testosterone decrease in bilateral cryptorchidism, normal in unilateral.
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Varicocele
Dilated veins in pampiniform plexus due to an increase in venous pressure; most common cause of scrotal enlargement in adult males; most often on left side because of increase resistance to flow from left gonadal vein drainage into left renal vein; can cause infertility because of an increase in temperature; bag of warms on palpation; diagnose by ultasound with Doppler; does not transilluminate. Treatment is varicocelectomy, embolization by interventional radiologist.
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Extragonadal germ cell tumors
arise in midline locations. In adults, most commonly in retroperitoneum, mediastinum, pineal, and suprasellar regions. In infants and young children, sacrococcygeal teratomas are the most common.
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Scrotal masses
Benign scrotal lesions present as testicular masses that can be transilluminated (vs solid testicular tumors).
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Congenital hydrocele
common cause of scrotal swelling in infants, due to incomplete obliteration of processus vaginalis. Transilluminating swelling.
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Acquired Hydrocele
Benign scrotal fluid collection usually secondary to infection, trauma, tumor. If bloody, it is a hematocele.
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Spermatocele
Cyst due to dilated epididymal duct or rete testis. Paratesticular fluctuant nodule.
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Testicular germ cell tumors
95% of all testicular tumors. Most occur in young men. Risk factors include cryptorchidism, Kliefelter syndrome. Can present as a mixed germ cell tumor. Differential diagnosis for testicular mass that dos not transilluminate: cancer.
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Seminoma
Testicular germ cell tumor. Malignant; painless, homogenous testicular enlargement; most common testicular tumor, most common in 3rd decade, never in infancy. Large cells in lobules with watery cytoplasm and fried egg appearance. An increase in placental ALP (alkaline phosphate). Radiosensitive. Late metastasis, excellent prognosis.
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Yolk sac (endodermal sinus) tumor
Testicular germ cell tumor. Yellow, muscinous. Aggressive malignancy of testes, analogous to ovarian yolk sac tumor. Schiller-Duval bodies resemble primitive glomeruli. An increase in alpha fetoprotein is highly characteristic. Most common testicular tumor in boys under three years of age.
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Choriocarcinoma
Testicular germ cell tumor. Malignant, an increase in hCG. Disorder syncytiotrophoblastic and cytotrophoblastic elements. Hematogenous metastases to lungs and brain (may present with hemorrhagic stroke due to bleeding into metastasis. May produce gynecomastia, symptoms of hyperthyroidism (hCG is structurally similar to LH, FSH, TSH).
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Teratoma
Testicular germ cell tumor. Unlike in females, mature teratoma in adult males may be malignant. Benign in children. An increase in hCG and/or alpha fetoprotein in 50% of cases.
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Embryonal carcinoma
Testicular germ cell tumor. Malignant, hemorrhagic masses with necrosis; painful; worse prognosis that seminoma. Often glandular/papillary morphology. Pure embryonal carcinoma is rare; most commonly mixed with other tumor types. May be associated with increased hCG and normal alpha fetoprotein levels when pure (an increase of alpha fetoprotein when mixed).
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Testicular non-germ cell tumors
5% of all testicular tumors. Mostly benign.
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Leydig cell tumor
Testicular non-germ cell tumors. Contains Reinke crystals (eosinophilic cytoplasmic inclusions); usually produce androgens leading to gynecomastia in men, precocious puberty in boys. Golden brown color.
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Sertoli cell tumor
Testicular non-germ cell tumors. Androblastoma from sex cord stroma.
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Testicular lymphoma
Testicular non-germ cell tumors. Most common testicular cancer in older men. Not a primary cancer; arises from metastatic lymphoma to testes. Aggressive.
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benign prostatic hyperplasia
common in men over 50 years old. Characterized by smooth, elastic, firm nodular enlargement (hyperplasia not hypertrophy) of periurethral (lateral and middle) lobes, which compress the urethra into a vertical slit. Not premalignant. Often presents with an increase frequency of urination, nocturia, difficulty starting and stopping urine stream, dysuria. May lead to distention and hypertrophy of bladder, hydronephrosis, UTIs. An increase in free prostate specific antigen (PSA). Treatment includes alpha 1- antagonists (terazosin, tamsulosin), which cause relaxation of smooth muscle; 5 alpha reductase inhibitors (eg finasteride); PDE-5 inhibitors.
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Prostatitis
Dysuria, frequency, urgency, low back pain. Acute causes include bacterial (eg E. coli); chronic causes include bacterial or abacterial (most common).
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Prostatic adenocarcinoma
Common in men over 50 years old. Arises most often from posterior lobe (peripheral zone) of prostate gland and is most frequently diagnosed by an increase of PSE and subsequent needle core biopsies. Prostatic acid phosphate (PAP) and PSA are useful tumor (an increase in total PSA, with a decrease fraction of free PSA). Osteoblastic metastases in bone may develop in late stages, as indicated by lower back pain and an increase in serum ALP and PSA. On histology, there are small neoplastic glands with prominent nucleoli amid normal prostate stoma.
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Leuprolide mechanism
GnRH analog with agonist properties when used in a pulsatile fashion; antagonist properties when used in continuous fashion (downregulates GnRH receptor in pituitary leading to a decrease in FSH/LH). Leuprolide can be used in lieu of GnRH.
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Leuprolide clinical use
Infertility (pulsatile), prostate cancer (continuous use following androgen receptor blockade with flutamide), uterine fibroids (continuous), precocious puberty (conintuous).
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Leuprolide toxicity
antiandrogen, nausea, vomiting
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Estrogens (ethinyl estradiol, DES, mestranol) mechanism
Bind estrogen receptors.
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Estrogens (ethinyl estradiol, DES, mestranol) clinical use
Hypogonadism or ovarian failure, menstrual abnormalities, hormone replacement therapy in postmenopausal women; use in men with androgen dependent prostate cancer.
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Estrogens (ethinyl estradiol, DES, mestranol) toxicity
increase risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina in females exposed to DES in utero, an increase risk of thrombi. Contraindications include ER positive breast cancer, history of DVTs.
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Clomiphene
Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and an increase release of LH and FSH from pituitary, which stimulates ovulation. Used to treat infertility due to anovulation (eg PCOS). May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances.
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Tamoxifen
Antagonist at breast, agonist at bone and uterus; an increase risk of thromboembolic events and endometrial cancer. Used to treat and prevent recurrence of ER/PR a positive breast cancer.
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Raloxifene
Antagonist at breast and uterus; agonist at bone; increase risk of thromboembolic events but no increased risk of endometrial cancer (vs. tamoxifen); used primarily to treat osteoporosis.
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Hormone replacement therapy
Used for relief or prevention of menopausal symptoms (eg hot flashes, vaginal atrophy), osteoporosis (increase estrogen decrease osteoclast activity). Unopposed estrogen replacement therapy increases the risk of endometrial cancer, so progesterone is added. Possible increase cardiovascular risk.
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Anastrozole/ exemestane
Aromatase inhibitors used in postmenopausal women with ER positive breast cancer.
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progestins mechanism
Bind progesterone receptors, decrease growth and an increase in vascularization of endometrium
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progestins clinical use
Used in oral contraceptives and to treat endometrial cancer, abnormal uterine bleeding.
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Mifepristone (RU-486) mechanism
Competitive inhibitor of progestins at progesterone receptor
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Mifepristone (RU-486) clinical use
Termination of pregnancy. Administered with misoprostol (PGE1)
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Mifepristone (RU-486) toxicity
heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain.
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Oral contraception (synthetic progestins, estrogen)
estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge means no LH surge and no ovulation. Progestins cause thickening of cervical mucus, thereby limiting access of sperm to uterus. Progestins also inhibit endometrial proliferation, which makes the endometrium is less suitable to the implantation of an embryo. Contraindications include smoker over 35 years of age (increase risk of cardiovascular events), patients with history of thromboembolism and stroke or history of estrogen dependent tumor.
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Tebutaline, ritodrine
beta 2 agonists that relax the uterus; used to decrease contraction frequency in women during labor.
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Danazol mechanism
Synthetic androgen that acts as partial agonist at androgen receptors.
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Danazol clinical use
Endometriosis, hereditary angioedema
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Danazol toxicity
weight gain, edema, acne, hirsutism, masculinization, decrease HDL levels, hepatotoxicity.
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Testosterone, methyltestosterone mechanism
agonists at androgen receptors
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Testosterone, methyltestosterone clinical use
treats hypogonadism and promotes development of secondary sex characteristics; stimulation of anabolism to promote recovery after burn or injury.
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Testosterone, methyltestosterone toxicity
Causes masculinization in females; decrease in intratesticular testosterone in males by inhibiting release of LH (via negative feedback) leading to gonadal atrophy. Premature closure of epiphyseal plates. Increase in LDL, decrease in HDL>
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Finasteride
a 5-alpha reductase inhibitor (decrease conversion of testosterone to DHT). Useful in BPH and male pattern baldness.
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Flutamide
A nonsteroidal competitive inhibitor at androgen receptors. Used for prostate carcinoma.
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Ketoconazole
Inhibits steroid synthesis (inhibits 17, 20- desmolase). Used to treat PCOS to reduce androgenic symptoms. Side effects include gynecomastia and amenorrhea.
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Spironolactone
Inhibits steroid binding, 17 alpha hydroxylase and 17,20 desmolase. Used to treat PCOS to reduce androgenic symptoms. Side effects include gynecomastia and amenorrhea.
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Tamsulosin
alpha 1 antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for alpha 1AD receptors (found on prostate) vs vascular alpha 1B receptors.
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Sildenafil mechanism
inhibits PDE-5 causes an increase in cGMP, smooth muscle relazation in corpus cavernosum, an increase in blood flow, penile erection. Silfenafil, vardenafil, and tadalafil fill the penis.
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Sildenafil clinical use
erectile dysfunction
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Sildenafil toxicity
Headache, flushing, dyspepsia (heartburn), cyanopsia (blue-tinted vision). Risk of life threatening hypotension in patients taking nitrates.
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Minoxidil
direct arteriolar vasodilator. Clinical uses include androgenetic alopecia; severe refractory hypertension.
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Surface ectoderm
Epidermis; adenohypophysis (from Rathke pouch); lens of the eye; epithelial linings of oral cavity, sensory organs of ear, and olfactory epithelium; epidermis; anal canal below the pectinate line; parotid, sweat, and mammary glands. Pathology includes craniopharyngioma, which is a benign Rathke pouch tumor with cholesterol crystals, calcification.
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Neuroectoderm
Brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland), retina and optic nerve, spinal cord. Think CNS.
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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 the skull, odontoblasts, aorticopulmonary septum. Think PNS and non-neural structures nearby.
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Mesoderm
muscle, bone, connective tissue, serous linings of body cavities (eg peritoneum), spleen (derived from foregut mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, vagina, kidneys, adrenal cortex, dermis, testes, ovaries. Notochord induces ectoderm to form neuroectoderm (neural plate). Its only postnatal derivative is the nucleus pulposus of the intervertebral disc. Middle/meat layer Mesodermal defects=VACTERL Vertebral defects, Anal atresia, Cardiac defects, Tracheo- Esophogeal fistula, Renal defects, Limb defects (bone and muscle)
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Endoderm
Gut tube epithelium (including anal canal above the pectinate line), most urethra (derived from urogenital sinus), luminal epithelial derivatives (eg lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells). Enternal layer.
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agenesis
absent organ due to absent primordal tissue
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aplasia
absent organ despite presence of primordial tissue.
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hypoplasia
incomplete organ development; primordial tissue present.
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deformation
extrinsic disruption; occurs after embryonic period.
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disruption
secondary breakdown of previously normal tissue or structure (eg amniotic band syndrome)
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malformation
intrinsic disruption; occurs during embryonic period (weeks 3-8)
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sequence
abnormalities result from a signal primary embryologic event (eg oligohydramnios leading potter sequence).
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Teratogens
most susceptible in 3rd-8th weeks (embryonic period, organogenesis) of pregnancy. Before week 3, all or none effects. After week 8, growth and function affected.
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Teratogenic effect of ACE inhibitors
causes renal damage
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Teratogenic effect of alkylating agents
causes absence of digits, multiple anomalies.
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Teratogenic effect of aminoglycosides
causes VIII toxicity. A mean guy hit the baby in the ear.
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Teratogenic effect of carbamazepine
causes facial dysmorphism, developmental delay, neural tube defects, phalanx/fingernail hypoplasia
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Teratogenic effect of diethystilbestrol (DES)
causes vaginal clear cell adenocarcinoma, congenital Mullerian anomalies.
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Teratogenic effect of folate antagonists
causes neural tube defects
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Teratogenic effect of isotretinoin
causes multiple severe birth defects. Contraception is mandatory with use.
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Teratogenic effect of lithium
causes ebstein anomaly (atrialized right ventricle)
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Teratogenic effect of methimazole
causes aplasia cutis congenita
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Teratogenic effect of phenytoin
causes fetal hydantoin syndrome, which includes cleft palate, cardiac defects, phalanx/ fingernail hypoplasia.
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Teratogenic effect of tetracyclines
causes discolored teeth. Teethacyclines.
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Teratogenic effect of thalidomide
causes limb defects (phocomelia, micromelia- flipper limbs)
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Teratogenic effect of Valproate
causes inhibition of maternal folate absorption, which causes neural tube defects.
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Teratogenic effect of warfarin
causes bone deformities, fetal hemorrhage, absorption, ophthalmologic abnormalities. Do not wage warfare on the baby; keep it heppy with heparin (does not cross placenta).
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Teratogenic effect of alcohol
causes common cause of birth defects and intellectual disability; fetal alcohol syndrome.
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Teratogenic effect of cocaine
causes abnormal fetal growth and fetal addiction; placental abruption
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Teratogenic effect of smoking (nicotine, CO)
causes low birth weight (leading cause in developed countries), preterm labor, placental problems, intrauterine growth restriction (IUGR), ADHD. Nicotine causes vasoconstriction. CO causes impaired O2 delivery.
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Teratogenic effect of iodine (lack or excess)
congenital goiter or hypothyroidism (cretinism)
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Teratogenic effect of maternal diabetes
causes caudal regression syndrome (anal atresia to sirenomelia- mermaid syndrome), congenital heart defects, neural tube defects.
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Teratogenic effect of vitamin A excess
causes extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac)
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Teratogenic effect of x-rays
causes microcephaly, intellectual disability.
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Fetal alcohol syndrome
leading cause of intellectual disability in the US. Newborns of alcohol-consuming mothers have had increased incidence of congenital abnormalities, including pre and postnatal developmental retardation, microcephaly, facial abnormalities (eg smooth philtrum-the vertical groove between the base of the nose and the border of the upper lip, hypertelorism-an increased distance between the orbits), limb dislocation, heart defects. Heart lung fistulas and holoprosencephaly in most severe form. Mechanism is failure of cell migration.
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twinning
dizygotic twins arise from 2 eggs that are separately fertilized by 2 different sperm (always 2 zygotes) and will have 2 separate amniotic sacs and 2 separate placenta (chorions). Monozygotic twins arise from 1 fertilized egg (1 egg plus 1 sperm) that splits into 2 zygotes in early 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 and the number amnions.
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placenta
first site of nutrient and gas exchange between mother and fetus. fetal component includes cytotrophoblast and syncytiotrophoblast. maternal component includes decidua basalis.
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cytotrophoblast
fetal component. the inner layer of chorionic villi. Cytotrophoblast makes cells.
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syncytiotrophoblast
fetal component. outer layer of chorionic villi; secretes hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first trimester. Lacks MHC-1 expression, which leads to a decrease in chance of attack by maternal immune system.
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Decidua basalis
maternal component. Derived from endometrium. Maternal blood in lacunae.
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Umbilical cord
contains umbilical arteries, umbilical vein, allatoic duct, wharton jelly, and amniotic apithelium
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Umbilical arteries
return deoxygenated blood from fetal internal iliac arteries to placenta. Single umbilical artery (2-vessel cord) is associated with congenital and chromosomal anomalies.
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Umbilical vein
suplies oxygenated blood from placenta to fetus; drains into IVC via liver or via ductus venosus. Umbilical arteries and vein are derived from allantois.
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Urachus
In the 3rd week the yolk sac forms the allantois, which extends into urogenital sinus. Allantois becomes the urachus, a duct between fetal bladder and yolk sac.
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Patent urachus
total failure of urachus to obliterate causing urine discharge from umbilicus.
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Urachal cyst
Partial failure of urachus to obliterate; fluid-filled cavity lined with uroepithelium, between umbilicus and bladder. Can lead to infection, adenocarcinoma.
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Vesicourachal diverticulum
slight failure of urachus to obliterate, which causes an outpouching of bladder.
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Vitelline duct
7th week, obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen.
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Vitelline fistula
Vitelline duct fails to close, causing meconium to discharge from umbilicus.
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Meckel diverticulum
partial closure of vitelline duct, with patent portion attached to ilium (true diverticulum). May have heterotopic gastric and/or pancreatic tissue, which causes melena, hematochezia, and abdominal pain
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1st aortic arch derivatives
Part of maxillary artery (branch of external carotid). 1st arch is maximal
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2nd aortic arch derivatives
stapedial artery and hyoid artery. Second=Stapedial
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3rd aortic arch derivatives
Common Carotid artery and proximal part of internal Carotid artery. C is 3rd letter of the alphabet.
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4th aortic arch derivatives
On left, aortic arch; on right, proximal part of right subclavian artery. 4th arch (4 limbs)=systemic.
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6th aortic arch derivatives
Proximal part of pulmonary arteries and (on left only) ductus arteriosus.
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Branchial apparatus
Also called pharyngeal apparatus. Composed of branchial clefts, arches, pouches. CAP covers outside to inside: Clefts=ectoderm, Arches=mesoderm, Pouches=endoderm.
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Branchial clefts
derived from the ectoderm. Also called branchial grooves. 1st cleft develops into external auditory meatus. 2nd through 4th clefts form temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme. Persistent cervical sinus causes branchial cleft cyst within lateral neck.
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Branchial arches
derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage).
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Branchial pouches
derived from endoderm.
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1st Branchial arch derivatives
Cartilage derivatives include Meckel cartilage: Mandible, Malleus, incus, spheno- Mandibular ligament. Muscle derivatives include Muscles of Mastication (temporalis, Masseter, lateral and Medial pterygoids), Mylohyoid, anterior belly of digastric, tensor tympani, tensor veli palatini. Nerve derivatives include CN V2 and V3 (chew).
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Treacher Collins syndrome
1st arch neural crest fails to migrate, which causes mandibular hypoplasia, facial abnormalities.
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2nd branchial arch derivatives
Cartilage derivatives include Reichert cartilage: Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament. Muscle derivatives include muscles of facial expression, Stapedius, Stylohyiod, platySma, posterior belly of digastric. Nerve derivatives include CN VII-facial expression (smile).
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Congenital pharyngocutaneous fistula
a persistence of 2nd branchial cleft and pouch, which leads to fistula between tonsillar area and lateral neck.
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3rd branchial arch derivatives
Cartilage derivatives include the greater horn of the hyoid. Muscle derivative include stylopharyngeus (think of stylopharyngeus innervated by glossopharyngeal nerve). Nerve derivatives include CN IX (stylopharyngeus) swallow stylishly.
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4th-6th branchial arch derivatives
Cartilage derivatives include the thyroid, cricoid, arytenoids, corniculate, cuneiform. Muscle derivatives from the 4th arch includes most of the pharyngeal constrictors; cricothyroid, levator veli palatini. Muscle derivatives from the 6th arch include all intrinsic muscles of larynx except cricothyroid. 4th arch nerve derivative include CN X- superior laryngeal branch (simply swallow). 6th arch derivatives include CN X- recurrent branch (speak). Arch 3 and 4 form posterior 1/3 of tongue; arch 5 makes no major developmental contributions.
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1st Branchial pouch derivatives
Develops into middle ear cavity, eustachian tube, mastoid air cells. 1st pouch contributes to endoderm-lined structures of ear.
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2nd Branchial pouch derivatives
develops into epithelial lining of palatine tonsil.
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3rd Branchial pouch derivatives
Dorsal wings develop into inferior parathyroids. Ventral wings develop into thymus. 3rd pouch contributes to 3 structures (thymus, left and right inferior parathyroids). 3rd pouch structures end up below 4th pouch structures.
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4th Branchial pouch derivatives
Dorsal wings develop into superior parathyroids.
284
Branchial pouch derivative mnemonic
Ear, tonsils, bottom-to-top: 1. ear, 2. tonsils, 3. dorsal (bottom for inferior parathyroids), ventral (to=thymus), 4. top=superior parathyroids.
285
DiGeorge syndrome
Aberrant development of 3rd and 4th puches, causes T cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development). Associated with cardiac defects (conotruncal anomalies).
286
MEN 2A
mutation of germline RET (neural crest cells): adrenal medulla (pheochromocytoma), parathyroid (tumor): 3rd/4th pharyngeal pouch, parafollicular cells (medullary thyroid cancer): derived from neural crest cells; associated with 4th/5th pharyngeal pouches.
287
cleft lip
failure of fusion of the maxillary and medial nasal processes (formation of primary palate).
288
cleft palate
failure of fusion of the two lateral palatine processes or failure of fusion of lateral palatine processes with the nasal septum and/or median palatine process (formation of secondary palate). Cleft lip and cleft palate often go together.
