Repro 2 Flashcards
Anatomically, what is the cervix divided into?
Exocervix – lined by nonkeratinizing epithelium
Endocervix – lined by a single layer of columnar cells
What is the junction between the exocervix and endocervix called?
The transformation zone
What type of genetic material is found in HPV?
HPV is a DNA virus
Where does HPV typically infect?
The lower genital tract (vulva, vaginal canal, cervix), particularly the cervix in the transformation zone.
HPV is divided into high risk and low risk strains. What is this distinction based upon? What does the risk refer to?
DNA sequencing. High risk types are HPV strains associated with a greater risk of developing cervical carcinoma.
What are the 4 common high risk type of HPV?
16, 18, 31, 33
What are the two common low-risk types of HPV?
6, 11
What is the pathogenesis of the high-risk types of HPV?
High risk HPV produce E6 and E7 proteins, which result in increased destruction of p53 and Rb, respectively. Loss of these tumor suppressor proteins increases the risk for cervical intraepithelial neoplasia (CIN)
How is cervical intraepithelial neoplasia (CIN) characterized histologically?
koilocytic change
disordered cellular maturation
nucelar atypia
hyperchromatic (dark) nuceli
increased mitotic activity
high nuclear to cytoplasmic ratio
within the cervical epithelium
Cervical Intraepithial Neoplasia (CIN) is divided into grades based upon what? What are the grades?
CIN is divided into grades based upon the extent of epithelial involvement by the dysplastic cells.
CIN I – involves <1/3 thickness of the epithelium
CIN II – involves <2/3 thickness of the epithelium
CIN III – involves slightly less than entire thickness
Carcinoma in situ – involves entire thickness of epithelium
What is cervical carcinoma?
cervical intraepithelial neoplasia that has progressed to become invasive carcinoma; CIN that has invaded the unerlying tissue
What is the most common demographic for cervical carcinoma?
middle-aged women (average age is 40-50 years)
How does cervical carcinoma present?
vaginal bleeding, especially post-coital bleeding
or cervical discharge
What is the key risk factor for cervical carcinoma?
Infection with high-risk HPV (16, 18, 31, 33)
What are the secondary risk factors for cervical carcinoma?
smoking
immunodeficiency (cervical carcinoma is an AIDS-defining illness)
What are the two most common subtypes of cervical carcinoma?
squamous cell carcinoma (80%)
adenocarcinoma (15%)
Both types are related to HPV infection.
What is the characteristc way cervical carcinoma spreads? What is a common cause of death in advanced cervical carcinoma?
Cervical carcinoma tends to invade locally through the anterior uterine wall into the bladder, blocking the ureters.
Hydronephrosis with post-renal failure is a common cause of death in advanced cervical carcinoma.
What is the gold standard for cervical cancer screening?
Pap smear
What are some limitations of the Pap smear?
- inadequate sampling of the transformation zone (false negative)
- limited efficacy in screening for adeenocarcinoma
(despite pap smear screening, the incidence of adenocarcinoma has not decreased significantly)
What subtypes of HPV does the vaccine cover?
The vaccine is a quadrivalent vaccine that covers types 6,11, 16, and 18
What do the antibodies generated against HPV subtypes 6 and 11 protect against?
chondylomas
What do the antibodies generated against HPV subtypes 16 and 18 protect against?
Cervical intraepithelial neoplasia (CIN) and carcinoma
How long does the protection last with the HPV vaccine?
5 years
Does a woman vaccinated against HPV need to get pap smears? Why?
Yes!
Pap smears are necessary due to the limited number of HPV types covered by the vaccine.
What is the functional unit of the ovary?
The follicle
What cells make up an ovarian follicle?
An ovum surrounded by granulosa and theca cells.
What hormone acts on the theca cells? What does it do?
LH
stimulates the theca cells to produce androstenedione from cholesterol (via desmolase)
What hormone acts on the granulosa cells of the follicle? what does it do?
FSH
stimulates the granulosa cells to convert androstenedione to estradiol (via aromatase)
This drives the proliferative phase of the endometiral cycle.
Coarctation of the aorta is associated with what chromosomal abnormality?
Turner syndrome, XO
What are the characterists of turner syndrome?
short stature
lack of fully developed ovaries (ovarian dysgenesis) –> decreased estrogen levels –> increased LH and FSH
bicuspid aortic valve
coarctation of the aorta
lymphatic defects (–>lymphedema of the feet, hands)
horseshoe kidney
What cardiac defectsw are pateints with Turner syndrome at risk for?
Coarctation of the aorta
bicuspid aortic valve
In a vasectomy, what structure is transsected to achieve permanent birth control?
The ductus deferens; it is tied in two places, and transsected
What is the most common location of ectopic pregnancy?
The ampulla of the fallopian tube.
A woman of reproductive age comes in with a recent history of amenorrhea, lower-than-expected rise in hCG based on dates, and sudden onset lower quadrant pain. What diagnosis should be suspected? What are the risk factors for this condition?
ectopic pregnancy
Risk factors include:
hx of infertility
salpingitis (PID)
ruptured appendix
prior tubal surgery
“honeycombed” uterus, or “clusters of grapes” or “snowstorm” on ultrasound are indicative of what condition?
Complete hydatidiform mole.
List the serious infections in pregnancy that are associated with morbidity and mortality of the fetus and newborn.
ToRCHeS
Toxoplasmosis
Rubella
Cytomegalovirus
Herpes/HIV
Syphilis
How is the distinction between placenta previa and placental abruption classically made clinically?
The distinction between placenta previa and placental abruption is classically made based upon the presence (abruption) or absence (previa) of pain.
(both can result in bleeding in the third trimester)
What are the risk factors from placental abruption?
HTN
smoking
cocaine use
preeclampsia
short umbilical cord
trauma (e.g., car accident)
prior abruption
What is mittelschmerz?
Transient, mid-cycle ovulatory pain; classically associated with peritoneal irritation 2º to bleeding from the rupture of a mature follicle.
What types of genes are BRCA 1 and BRCA 2?
BRCA 1 and BRCA 2 are tumor suppressor genes whose proteins function in DNA repair.
What type of mutations affect the BRCA 1 and 2 genes?
Nonsense and frameshift mutations, with lead to gene products with less or no function (loss of function mutation)
What clinical diseases are associated with the BCRA 1 and BRCA 2 genes?
breast cancer
ovarian cancer
What is an adnexal mass?
The adnexa of the uterus are the structures that are most closely related structurally and functionally to the uterus (fallopian tubes and ovaries)
An adnexal mass is a mass in the fallopian tube or ovary.
What is Meig’s syndrome?
The triad of ovarian tumor, ascites, and pleural effusion.
Cleavage at what stage would result in monozygotic, dichorionic, diamniotic twins?
Cleavage of the morula days 1-3
Cleavage at what stage would result in monozygotic, monochorionic, diamniotic twins?
Cleavage of the blastocyst days 4-8
Cleavage at what stage would result in monozygotic, monochorionic, monoamniotic twins?
Cleavage of the blastocyst days 8-13
Cleavage at what stage would result in monozygotic, conjoined twins?
Cleavage of the formed embryonic disc, days 13-15
What is PID? What are the most common causes?
Infection of the uterus, fallopian tubes, and possibly the ovaries.
Most common causes/pathogens:
Chlamydia trachomatis
Neisseria gonorrhoeae
What are the classic symptoms of PID?
cervical motion tenderness
purulent cervical discharge
fever
(Classic triad of fever, abdominal pain (bilateral), and discharge)
PID may include salpingitis, endometritis, hydrosalpinx (distally blocked fallopian tube with serous/clear fluid), and tubo-ovarian abcess.
What is Fitz-Hugh-Curtis syndrome? How does it present?
Perihepatitis; a complication of PID that involves infection of the liver capsule and “violin string” adhesions of the peritoneum to the liver.
Presents with right upper quadrant pain associated with symptoms of PID.
What is placenta previa?
Placenta previa occurs when the placents overlies the cervical os (opening). It can be described as complete, partial, or marginal.
It can be associated with painless bleeding in the third trimester of pregnancy.
What is placenta accreta?
This refers to the abnormally strong adherence of the placenta to the uterine wall because the placental villi attache directly to the myometrium due to a defect in the decidua basalis layer.
What hormone is responsbile for the formation of normal male external genitalia in utero?
DHT
(dihydrotestosterone)
How is it possible to use temperature to determine when a woman ovulates?
Progesterone is produced by the corpus luteum shortly after ovulation. One of the roles of progesterone is to increase the basal body temperature; one of its locations of action is the hypothalamic thermoregulatory center. Basal body temperature may increased by up to 1º.
It’s therefore possible to determine when ovulation occurred by checking one’s basal body temperature every day.
What is mifepristone? What is it used for?
Mifepristone is a partial progesterone agonist with antagonist properties.
Progesterone is necessary for the maintenance of pregnancy; administration of mifepristone will result in abortion of the embryo.
What two drugs are often used together to ensure efficacy of a medical abortion?
- Mifepristone (partial progesterone agonist)
- Misoprostol (a prostaglandin E1 agonist with oxytocin-like effects)
What is misoprostol? What is it used for?
A prostaglandin E1 agonist that stimulates contraction of the uterus (therefore mimicking the effect of oxytocin).
It is often used in conjunction with mifepristone to induce medical abortion.
What is a dominant negative mutation?
Dominant negative effects occur when the loss of one allele leads to disease.
(This is either because the body cannot produce enough of the protein product with just one functioning allele, or because the mutated allele produces an altered gene product that is antagonistic to the wild-type allele)
Which of the following is exemplified by Burkitt’s lymphoma?
chromosomal rearrangement
dominant negative effect
gain of function
loss of function
viral insertion
Gain of function
oncogenes can acquire gain-of-function mutations that lead to increased activity of the gene product, which causes uninhibited cellular proliferation.
This typically occurs in a single allele of the oncogene and acts in a dominant fashion.
How does breastfeeding prevent ovulation?
Breastfeeding stimulates prolactin release from the anterior pituitary.
Prolactin prevents ovulation by inhibiting GnRH release from the hypothalamus. The decrease in GnRH –> a decreased in LH and FSH from the anterior pituitary, which then prevents ovulation.
What is the most specific serological test for syphilis?
The FTA-ABS (fluroescent treponemal antibody absorption test).
Compared to the venereal disease research laboratory (VDRL) test, the FTA-ABS test is more specific, turns positive earlier in the disease, and remains positive longer.
Compare the FTA-ABS test to the VDRL test. For what are these tests used to screen/diagnose?
These tests are used to screen and diagnose syphilis.
Compared to the venereal disease research laboratory (VDRL) test, the FTA-ABS test is more specific, turns positive earlier in the disease, and remains positive longer.
What is 5 alpha-reductase deficiency?
Autosomal recessive deficiency of 5 alpha-reductase, which leads to an inability to convert testosterone to DHT. This disorder is sex-limited to genetic males.
How does 5 alpha-reductase deficiency present? Relative to normal, what are the levels of testosterone, estrogen and LH levels in these patients?
Patients have ambiguous genitalia until puberty, when the increase in testosterone causes masculinization and growth of the external genitalia.
Testosterone, estrogen and LH levels in these patients are all normal.
What is aromatse deficiency?
Inability to synthesize estrogens from androgens.
Presents as masculinization of female (46, XX) infants (ambiguous genitalia); can present with maternal virilization during pregnancy (fetal androgens cross the placenta).
serum testosterone and androstenedione are high.
Besides its use in medical abortion, what other conditions is misoprostol used for?
Misoprostol is a prostaglandin E1 agonist.
It can also be used to treat NSAID-induced gastric ulcers. It does this by increasing the secretion of mucus to protect the mucosal lining.
How does NSAID use lead to the formation of a gastric ulcer?
The gastric mucosa protects itself from gastric acid with a layer of mucus. The secretion of this mucus is stimulated by prostaglandins.
NSAIDs inhibit cyclooxygenase, which inhibits the formation of prostaglandins. This in turn decreases mucus production, and makes the gastric mucosa more susceptible to ulcer.
What is the first-line treatment for syphilis?
Penicillin G.
Penicillin G is a ß-lactam bactericidal antibiotic. It causes bacterial cell lysis by interfering with transpeptidase cross-linking of the cell wall.
What are the two most common infections that cause PID?
Chlamydia trichomatis and Neisseria gonorrhoeae.
What is the first-line treatment for chlamydia? What kind of drug is it?
Azithromycin.
This is a macrolide antibiotic
What is the first-line treatment for gonoccal infections? What kind of drug is it?
Ceftriaxone
This is a third-generation cephalosporin.
What is used to treat herpes simplex infections?
acyclovir
What is the first-line treatment for UTIs?
Trimethoprim-sulfamethoxazole, also known as Bactrim
What is the most common sexually transmitted bacteria?
Chlamydia
How can chlamydia lead to ectopic pregnancy?
Chlamydia is the most common sexually transmitted bacteria, and can cause PID and scarring of the fallopian tubes. PID is a risk factor for ectopic pregnancy
Why would late menopause be a risk factor for endometiral cancer?
Endometrial carcinoma is an estrogen-dependent neoplasm that results from exposure to high levels of estrogen in the absence of progesterone. Late menopause results in a longer period of exposure to unopposed estrogen acting on the endometirum.
What is the genotype and genetic content of a complete hydatidiform mole
46, XX consisting completely of paternal DNA
How/why does a complete hydatidiform mole from?
It forms when two sperm fertilize an empty egg.
What is the decidua basalis?
This is the maternal component of the placenta. It is derived from the endometrium.
Male or female, which is the default development?
Female.
The mesonephric (Wolffian) duct degenerates, and the paramesonephric (Mullerian) duct develops.
What do the paramesonephric ducts develop into?
In the absence of Mullerian Inhibiting Factor, the paramesonephric ducts develop into uterine tubes and fuse caudally to form the female internal structures:
fallopian tubes
uterus
cervix
upper 1/3 of the vagina
What is the cause of a bicornuate uterus? What is associated with this condition?
Incomplete fusion of the paramesonephric ducts.
This is associated with infertility and urinary tract abnormalities.
What therapy targets the her2/neu receptor in breast carcinoma? What type of drug is it?
Trastuzumab, which is a monoclonal antibody against HER2
All drugs ending in “mab” are what kind of drug?
A monoclonal antibody.
What does bevacizumab target?
Vascular endothelial growth factor.
What drug would be useful in estrogen receptor-positive breast cancer? How does it work?
Tamoxifen.
Tamoxifen binds the intracellular estrogen receptor and blocks it. This blocks the production of estrogen-responsive genes.
