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Glossary of Generations Final

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define INFERTILITY
1 year of unprotected intercourse without conception
Primary infertility = ?
infertility with NO PRIOR CONCEPTION
Secondary infertility = ?
infertility WITH a prior conception
how long can sperm survive in reproductive tract?
3-5 days
When can an oocyte be successfully fertilized?
12-24 hours after ovulation
When is "timed coitus" most likely to be successful?
5 days before ovulation up to the day of ovulation
What are some of the reasons (6) that birth rates have gone from 55/1000 pop to 14.1/1000 pop, from 1790 to 2001 (and fert rates from 106.2/1000 women 15-44 in 1950 to 65.3/1000 women 15-44 in 2001)?
>advanced education and careers for women; childbearing delayed
>Marriage issues - later marriage & more frequent divorce
>family planning-desire for smaller families and better contraception
What challenges do older women face in becoming pregnant?
pregnancy rate decreases, while spontaneous abortion increases
What are some changes in the menstrual cycle as women age?
1) follicular phase is SHORTER
2) DOMINANT FOLLICLE is selected earlier
3) There are FEWER follicles SO: LESS ESTROGEN is produced, LESS Inhibin A and B produced, HIGHER levels of FSH
Why does oocyte aneuploidy increase with age?
1) premature separation of sister chromatids in meiosis I (d/t changes in cohesins, preventing alignment of sister chromosomes on meiotic spindle, before they separate)
2) Whole chromosome nondisjunction in meiosis II
3)
oocytes present at 1) 16-20 wks gestation _____ 2) at birth ____ 3) at puberty onset ____ 4) ages 37-38 ___ 5) at menopause
1) 6-7 million
2) 1 million
3) 300-500K
4) 25K
5) 1K
What are some (3) GENERAL causes of male infertility (after correcting for woman's age)?
1) sperm volume goes down
2) sperm motility goes down
3) sperm morphology aberrations
What are some (5) of the physiology changes in male reproductive system as men age?
1) seminiferous tubule sclerosis
2) germ cell & Leydig cell # decrease
3) decreased testosterone
4) increased FSH
5) more sperm chromosomal damage
What history components (6) are important for evaluating a woman with fertility probs?
Prior pregnancy outcomes
Cycle length, dysmenorrhea
Prior infertility testing?
PM/SH
Tobacco? Alcohol?
Family hx of early menopause
Coital frequency, lubrication
What history components (8) are important for evaluating a man with fertility probs?
Prior pregnancies?
Coital frequency?
Previous testing?
Childhood illness (mumps)
Previous surgery
Environmental toxins?
Medications?
Smoking? Alcohol?
What important physical exam components (8) should be done when evaluating a woman w/fert probs?
Weight, BMI
Thyroid enlargement?
Breast discharge?
Hirsutism?
Normal pelvic exam? Tenderness in cul de sac? Uterine tenderness?
Cervical discharge?
What important physical exam components (5) should be done when evaluating a man w/fert probs?
Location of urethral meatus
Testicular size
Presence of vas deferens, epididymis
Varicocele?
Body habitus, hair distribution
What are some basic tests to determine why couple is infertile (5)?
1) ovulatory function
2) ovarian reserve
3) semenalysis
4) tubal patency (hysterosalpingogram)
5) laparoscopy
When determining why a couple is infertile, what do you assess with ovarian function testing (4)?
1) regular menses?
2) luteal phase progesterone (marker for ovulation)
3) basal body temp (progesterone effect on hypothalamus)
4) use an ovulation predictor
When determining why a couple is infertile, what is assessed when examining ovarian reserve?
FSH is measured on cycle day 3
When determining why a couple is infertile, why is a hysterosalpingogram done?
To make sure there is adequate Fallopian tube diameter. Should see no spill of dye into abdomen.
How do you induce ovulation in women with PCOS?
1) Clomiphene citrate (antiestrogen)
2) injectable gonadotropins if clomiphene doesn't work
How do you induce ovulation in women with hyperprolactinemia?
Parlodel
What else can you use injectable gonadotropins for (aside from clomiphene resistant PCOS)?
inducing ovulation in hypothalamic amenorrhea
What conditions lead to anovulation that can be treated?
1) PCOS 2) hyperprolactinemia
3) hypothalamic amenorrhea
What is easiest type of infertility to treat? (1 glaring exception)
ovulation disorders (except (premature) ovarian failure)
What are some (3) TX options for infertility caused by a tubal factor?
1) IVF 2) tubal surgery
3) tx Endometriosis
What are some (3) TX options for infertility caused by Ovulatory dysfunction?
1) Clomiphene 2) parlodel, 3) injectable gonadotropins
What are some (3) TX options for infertility caused by a factor in the Male partner?
1) Intrauterine insemination (IUI),2) IVF, 3) donor sperm
What are some (3) TX options for Unexplained infertility?
Clomiphene or gonadotropins with hCG & IUI,
or IVF
Clom combo-25-30% preg in 4 mos
IG combo - 40% preg in 4 mos
What are some (6) of the clinical features of endometriosis?
Reproductive Aged Women
Pelvic Pain, Infertility
Early Menache, Short Cycles
Incidence 6 – 7 X In 1st Degree Relatives
Surg management = Med management for pain management in endometriosis, T or F
True
What is easiest infertility cause to tx?
Ovulation disorders (except if there's ovarian failure)
What fert probs (3) can the clomiphene citrate/hCG/IUI?
1) unexplained
2) male factor
3) minimal endometriosis
Why does endometriosis cause infertility (4)?
Anatomic Distortion
Abnormal Eutopic Endometrium
Disorders of Ovulation
Abnormal Peritoneal Fluid
What are 5 goals in surg tx of endometriosis?
Restore Normal Anat & Mobility
Remove All Visible Disease
Know Atypical Appearance
Excise Deep Disease and Endometriomas
Prep Bowel & UT Disease
What are the 3 qualities about Embryonic stem cells (ES cells)?
1) immortal
2) pluripotent
3) undifferentiated
Where do you get ES cells from?
inner cell mass (of epiblast) from pre-implantation blastocyst (less than 1 wk old)
What are biggest risks of using injectable gonadotropins for tx'ing fert probs?
ovarian hyperstimulation and multiple gestations (less of prob w/IVF)
What is the fate of ES cells?
1) divide w/o differentiating (long term self-renewal)
2) differentiation into germ or somatic cells
Clonogenic means = ?
a single ES cell can give rise to colony of gen identical cells (clones) - same properties as the original cell
factors for self-renewal (4):
1) basic FGF
2) Wnts
3) Noggin
4) Oct 3/4 (extrinsic)
What are some of the major challenges of ES cells (biomedical standpoint)? (3)
1) efficacious?
2) safe?
3) will they be rejected?
somatic cell nuclear transplant = ?
removal of oocyte nucleus which is replaced by pt's somatic cell nucleus
therapeutic cloning steps
1) somatic cell nuclear transplant
2) cell division stimulation up to blastocyst stage
3) harvest inner cell mass for ES cells
therapeutic cloning goals
these cells would be matched to pt's immune system - so no immunosuppressants would be needed
Monthly chance of conception?
10%
Chance for multiples in pregnancy?
1%
there is an epidemic of infertility? T or F
False
What steps does IVF involve?
-->Harvest of multiple mature ovulatory human oocytes
-->Extracorporeal fertilization (outside the body)
-->Subsequent replacement of a limited number of day 3 post fertilization embryos into the recipient’s uterus
fecundability = ?
probability that 1 cycle will result in pregnancy
fecundity = ?
probability that 1 cycle will result in live birth
What is the Wyden bill of 1992 for?
TO make fert clinic success rates known to public (CDC and SART publish auditable info)
IVF is a last resort tx - T or F?
False
Intracytoplasmic Sperm Injection (ICSI) tx's
male factor infertility
Intracytoplasmic Sperm Injection (ICSI) involves what procedure?
injecting single sperm directly into egg
Gestational carrier = ?
intended father's sperm; surrogate egg
Gestational surrogacy = ?
intended father's sperm; intended mother's egg
6 reasons for a poor sperm count
smoking, alcohol, trauma, drugs, toxins, genetic (CF, Y microdeletions)
ICSI makes 4 processes possible:
1) Sperm freezing before or during chemotherapy
2) Sperm freezing at vasectomy reversal
3) Microsurgical epididymal sperm aspiration (MESA)
4) Testicular sperm extraction (TESE, ROSNI)
risk of ICSI seems to be ___?
No increase in miscarriage, slight increase in birth defects
In semenalysis, what are the criteria for normal, healthy male fertility?
Volume : >1 Ml
Count: 20 million/ml
Motility: >50% moving
Morphology:
>30% normal (WHO)
>4% normal forms (Kruger’s strict)
Why do sperm counts seem to be declining?
1) 2% decline/yr of birth
2) Enviromental endocrine disruptors
3) Urban Vs rural
4) Increasing incidence of testicular cancer and undescended testicles
what are the success rates of various tubal reconstructive surgeries and how do they compare to IVF?
Removing pelvic adhesions: 50-70% (better)
Repairing partially blocked tube: 40-60% (better)
Opening damaged tube: 15-25%
Salvage operative laparoscopy: 5-15%
IVF: 30-40%
What are some disadvantages of tubal reconstructive surgery?
1) Long time to pregnancy
2)High incidence of ectopic pregnancy (>5 % Vs 0.3 to 3% at IVF)
3) Major morbidities
4) High cost
5 IVF complications
Cost
Multiple pregnancy
Ovarian hyperstimulat'n synd
Risks of retrieval- Bleeding
& Infection
Birth defects
IVF reduces multiple pregnancies - T or F?
True
Implanting more embryos increases chances of successfully becoming pregnant - T or F?
False - just increases chances of mult pregnancies
What are 5 reasons repro surg is done in the IVF era?
1) remove hydrosalpinges
2) remove ov cysts
3) remove endometriomas
4) ensure vaginal ovarian access
5) normalize the uterine cavity
What's so great about removing hydrosalpinges?
1) improves pregnancy rates
2) decreases aspiration complications
3) improves transvaginal ovarian access
What kinds of birth defects do you see w/ART?
1) small for gestational age
2) sex chrom disorders w/ICSI
3) congen anomalies (2x risk)
4) ?Imprinting disorders (Beckwith-Wiedeman, Angelman)
What are the indications (3) for doing donor oocyte IVF?
Indications:
1) Diminished ovarian reserve
2) Multiple miscarriage
3) Maternal chromosomal anomaly
What factors (5) diminish ovarian reserve?
Smoking
Age
Ovarian surgery
High altitude
Chemotherapy/radiation therapy
What is "assisted hatching" IVF?
Slit zona pellucida of embryos prior to transfer
What phenomenon does "assisted hatching" increase?
Chances for monozygotic twins
"assisted hatching" is used to improve
implantation rate in >38 yo, previous failed IVF w/good embryos, thick zona
drawback of cytoplasmic donation (donor oocyte cytoplasm into old oocyte - improves chances of preg):
mitochondrial DNA transfer from donor
What's good (1) and what's bad (3) about new BLASTOCYST TRANSFER technique?
good- 50-70% preg rate BUT
difficult culture technique
freq failure of blast dev
appreciable multiple rate
What is preimplantation genetic dx (PGD)?
Single cell biopsy and amplification or staining of DNA
What is PGD used for?
1) dx- gen dz (1 gene-CF,HD)
2)ID chrom abnorm embryos (DS)
3) sex selection
4) select favorable chars
5) gen engineering
WHat's the difference between reproductive cloning and therapeutic cloning?
Nuclear transfer blastocyst - tx'ic - harvest ES cells...
repro - implant into female uterus
MENOPAUSE definition
Last menstrual cycle; no menses for 1 yr
age of menopause
median - 51;
range - 40-57
best predictor of menopause?
age of menopause of female relatives (genetic)
earlier (but not premature) menopause is related to... (3)?
1) Gyn surg (uterus, ovaries)
2) smoking
3) chronic malnutrition
premature ovarian failure is caused by...(5)?
1) idiopathic
2) chrom abnorms - Turner, Fragile X
3) radiation tx (>800 rads)
4) chemo (esp alkylating agents, cyclophosphamide - 60%)
5) autoimmune endocrinopathies (parathyroid, thyroid, adrenal)
PERIMENOPAUSE definition
defined by onset of irregular menses - time between regular menses (pre) and final menses
age of perimenopause
av - 46; range 39-51
early, mid, late menopause defined by cycle length...
early <25 d, mid up to 90 d, late >90 d
climacteric sx of menopause are caused by:
loss of ovarian hormones
climacteric sx of menopause include (4)
1) vasomotor sx
2) vaginal/vulvar sx
3) mood changes
4) sexual changes
estrogen loss in perimenopause causes (4 and a possible)
1) vasomotor sx
2) vag/vulvar/bladder changes
3) loss of bone/osteoporosis
4) decreased breast tissue
?cognitive fnx, ?sexuality
progesterone loss in perimenopause causes
irregular menses
testosterone loss in perimenopause may cause...
1)vasomotor sx
2)muscle mass
3)sexuality
at menopause/perimenopause vasomotor sx = ?
hot flashes/night sweats - sudden onset head, neck, chest skin reddening, intense body heat, rapid HR, perspiration and chilling;
(might be caused by loss of estrogen effect on hypothalamus)
Who is affected by vasomotor sx at menopause/perimen?
85% women after menopause; 50% perimenopause; decreases 2 yrs after menopause
what are the vaginal/vulvar changes of menopause/peri?
vag dryness, thinning, dyspareunia, postcoital bleeding, vaginitis
(vag higher pH, loss of collagen, adipose, thin epith and subcut tissue) - 50% of women
bladder/pelvic changes during menopause
weakness of vag (caused by loss of m and collagen) - can prolapse w/uterus, bladder (cystocele), rectum (rectocele) or intestine (enterocele)
Bone loss in menopause (type)
trabecular bone
Bone loss in menopause (rate)
5%/yr early in menopause w/50% loss in 20 yrs
factors affecting bone loss (6)
genetics, dietary, meds, smoking, exercise, weight
dx of osteoporosis
DEXA hip and spine - greater than -2.5 SD on T score (osteopenia - -1 to -2.5); normal (0- (-1))
estrogen effect on cardiovascular system (3)
1) increases HDL
2) lowers LDL
3) endothelium pos effects - vasodilatation and lowers plaque
risks (3) of exogenous estrogen
1) thromboembolic events
2) CRP up
3) triglyceride levels up
breast changes w/menopause
decrease in glandular tissue density (adipose main tissue present allows easier mammo detection)
estrogen loss (menopausal) effects on cognition
unclear but may decrease verbal and ST memory (E may help prevent Alz, but stroke risk)
what were the results of the WHI?
HRT decreases: osteopor risk and colon ca risk
BUT increases: heart dz, breast ca, stroke, blood clots
FDA recommendations re: HRT
lowest dose for shortest time possible
5 ways to managem menopausal sx:
1) avoid stress
2) avoid heat
3) avoid EtOH
4) layered clothing
5) relaxation techniques
4 drug classes for menopausal sx management:
1) antidepressants (Effexor, Zoloft, Paxil)
2) nerve blockage - neurontin
3) sleep agents - Z class - ambien, lunesta
4) tachycardia - catapres patch
The story on soy...
no help w/menopausal sx. but lowers tot cholesterol, LDL, triglycerides (AHA, FDA)
the only herb to help w/menopausal sx...
black cohosh (Remifemin)
in order what reduces CV dz risk most
1) quit smoking
2) lose weight to <20% above IBW
3) exercise
2 things to prevent bone loss
weight bearing exercise, 1500 mg/d Calcium supplement
tx of T score <-2 SD or osteoporosis
1) SERM - Evista
2) bisphosphonate - Fosamax or Actonel- daily/weekly
3) Boniva - monthly
when would estrogen alone HRT be acceptable?
if woman has had hysterectomy (no risk of endometrial ca)
tx of vag sx of menopause
lube, topical vag estrogen tx, corticosteroids for vulvar/vag fissures, vaginitis tx if nec, keep having sex
urinary incontinence tx - post-men (4)
1) Kegel exercises
2) biofeedback/PT
3) pessary (also for uterine prolapse)
4) surg - collagen, bladder elevation
when is HRT indicated?
when sx affect QOL (sleep, daily activities, sex)
at menopause, how often is bone density screening indicated?
initial screen at menopause, and every 2 yrs if osteopenia present
at menopause, how often is Pap test screening indicated?
every 2 yrs if normal for 10 yrs
at menopause, how often is mammo screening indicated?
every yr
what happens to FSH w/menopausal changes?
increases
what happens to follicular phase length w/perimenopausal changes?
they get shorter d/t less FSH
what happens to menstrual cycle length w/perimenopausal changes?
they get shorter d/t shorter folicular phases
What happens to luteal phase length w/perimenopausal changes?
no change
Why is estradiol lower in peri/menopause?
b/c ovary not as responsive to FSH (even though increased!)
in perimenopause, why are there more anovulatory cycles?
b/c lower estradiol levels --> no LH surge
anovulation causes ___ cycles w/___menses:
longer cycles w/ normal/heavy menses - b/c low progesterone pdtn
anovulation with lowered estradiol (perimenopause) leads to ___ cycles
lighter cycles
perimenopause - gonadotropins, ____ increase/decrease
FSH, LH; increase
perimenopause - ovarian hormones, ___ , increase/decrease
estradiol, progesterone; decrease markedly
perimenopause - adrenal hormones ____, increase/decrease
dehydroepiandrosterone, testosterone; decrease
6 barriers to MDs and pts (5) discussing sexual health
1) cultural silence
2) personal discomfort
3) environ shift/role transformation (pt expectations)
4) inadequate/no sexual history training
5) what should I do w/info?
6) conflict between personal values and pt cntrd care
6 ways on how to better facilitate open, trusting environment re: sexual history
1) anti-discrim sign
2) waiting room materials - heteronorm/GLBT
3) unisex restrooms
4) more options to select on intake forms
5) well-trained staff (gender)
6) updated list of resources/referrals
when is sex/repro history assessed? (5)
1) routine health maint (primary care)
2) repro health visits
3) acute visits - sexual issues may be contrib to cause of CC
4) sexual assault/abuse concerns
5) whenever pt wishes
6 ways on how do you create a pos atmosphere for sexual history taking?
privacy, limited interruptions, pt dressed, eye level w/pt, culturally approp language, anat models/drawings
exceptions to confidentiality re: sexual history info gathering
reporting of STIs, sexual abuse of minor
High risk behaviors not sexual orientation put someone at risk, T or F?
True
What are 4 sx of poss prostate health probs?
1) pain w/ BMs
2) diff/pain w/urination
3) pain w/ejaculation
4) lower ab pain
chancroid is caused by _____
Hemophilus ducreyi
Hemophilus ducreyi is a Gram __ ____ (shape)
negative rod
HSV presentation:
multiple vesicles and ulcers
HSV painful/painless
Painful
syphilis presentation
indurated smooth borders w/clean base (chancre)
H. ducreyi presentation
tender papule --> painful ulcer w/sharp or ragged edges w/purulent base (opposite of what's seen in syphilis)
syphilis - painful/painless
painless
H.ducreyi painful/painless
VERY PAINFUL
LGV is caused by ___
C. trachomatis L1-L3
LGV painful/painless
painless
good test for H. ducreyi
PCR - sens and spec (hard to grow in culture, requires enriched media)
Tx for H ducreyi
oral Z-pack or IM ceftriaxone
erythromycin
How to prevent H ducreyi
abstinence/barrier
reservoir for herpes
humans are the only natural reservoir
sx of trichomonas
variable amt of poss malodorous, frothy, yellow-green discharge w/ or w/o itching; dysuria and dyspareunia; cervicitis poss - if cervix red and inflamed - strawberry cervic; asx'ic? 20-50% women; most men
if men show sx of H ducreyi, what will they be?
dysuria and clear discharge
Clinical signs of trichomonas
frothy discharge, vag wall redness, elevated vag pH (5-6 vs. 4.5)
how to dx trichomonas
vag discharge wet mount - darting motility
How to tx trichomonas - specific med and in general
med - metronidazole (Flagyl)
general - tx male partner
Candida vulvovaginitis caused by ______
OVERGROWTH of C. albicans (normal flora in 50% of women)
C. albicans overgrowth in Candida vulvovaginitis caused by (5) _____
1) ABX
2) poorly controlled diabetes
3) pregnancy
4) HIV
5) steroids
Candida can cause ____ in men
balanitis (but not very common)
sx of Candida vulvovaginitis
ITCHY!!!! white thick cottage cheese discharge (not so smelly) adheres to vag wall, vulvar/vag wall redness, scale/fissure of vulvar tissue, dyspareunia, dysuria
tx for Candida vulvovaginitis
azole anti-fungals (oral, topical, suppositories); male partner tx - unnecessary unless balanitis
most common form of vaginitis
bacterial vaginosis
spp causing bacterial vaginosis (3)
1) gardnerella vaginalis
2) mycoplasma spp
3) anaerobes
sx of bact vaginosis
if there are sx (many are asx'ic); thin gray-white SMELLY discharge, NOT ITCHY, less vag redness compared to yeasty/trich
dx of Candida vulvovaginitis
round Gram + yeast, 10% KOH - yeast w/hyphal elements - 70-90% sens; rapid latex agglutination - good sens
clinical signs of Candida vulvovaginitis
itchiness, vaginal/vulvar redness, cottage cheese; normal vag pH
the best dx'ic indicator of bacterial vaginosis
CLUE cells (sq cells w/adherent coccobacilli)
another way to dx bact vaginosis
Whiff test - 10% KOH - smells like fish!
how is bact vaginosis like trichomonas but unlike candida?
BV and Trich pH > the normal 4.5
painful ulcer, neg herpes test
H ducreyi
tx of bacterial vaginosis
7 days of metronidazole/Clindamycin; tx of partner DOES NOT prevent re-infection
Causes of prostatitis
bacterial (E coli, pseudomonas), unknown for non-bacterial and prostadynia
sx of acute bacterial prostatitis
SUDDEN perineal, sacral, suprapubic pain w/common chills/fever and irritative voiding sx (may need hosp)
sx of chronic bacterial prostatitis
like UTI sx, irritative voiding sx, mild perineal/suprapubic discomfort may or may be there...(similar for non-bact and prostadynia)
dx of bacterial prostatis
both acute and chronic - UA - pyuria & bacteriuria; urine cultures --> pathogenic bacteria
dx non-bacterial prostatitis
WBCs - prostatic fluid and urine; no bact growth in culture
dx of prostadynia
no bacteria/no WBCs on UA/prostatic secretions
tx of prostatitis/prostadynia
bact: acute:1-2 wks ABX,
chronic:4-12 wks ABX
non-bact and prostadynia - hot baths
HSV age groups
1- all; 2 - after puberty (unless sexual abuse)
% of adults seropositive for HSV-2
25
most common genital ulcer dz worldwide
80%
spread of HSV
by direct contact w/infected secretions; condoms - 40-50% effective at prevention; daily medication effective at preventing spread
primary HSV infections sx
painful ulcers at point of contact 5-7 d after sexual contact;
1/3 pts -systemic - fever, malaise, myalgia, adenopathy, 8% aseptic viral meningitis
recurrent genital herpes characteristics
shorter duration of outbreak,milder sx, localized to genitals,no systemic; ASX'ic shedding very common
difference in dz course between HSV-1 and HSV-2
HSV-2 much more likely to lead to reactivation (80% w/in 12 mos)
5 ways to dx HSV
1) Tzanck prep - giemsa/wright stain - multinucleation, molding, margination
2) ELISA
3) Pap smear
4) PCR
5) gold std - cell culture
tx of HSV
acyclovir, valacyclovir, famcyclovir - decrease duration and intensity of acute infections, prevents both sx'ic and asx'ic reactivation
HPV prevention - 4 ways
1) abstinence
2) barrier
3) Pap smear
4) vaccine
HPV vaccines
gardisil, cervarix; gardisil - quadrivalent (6/11/16/18)-virus like particle (VLP) vaccine; 3 doses, women between 9-26 yo; not rec for men yet
HPV tx
never 100% effective; exophytic warts resolve on own; cryotx, laser/surg/trichloroacetic acid removal
HPV dx (3)
1) Pap smear
2) HPV nucleic acid probe
3) colposcopy (after abnormal Pap)- acetowhitening
Sx of HPV
Often asx'ic esp in women (flat on cervix); types 6&11 - exophytic warts (condyloma acuminata)
Most common viral STD in USA
Condyloma acuminata (HPV 6/11)
HPV #'s assoc w/benign warts
6 and 11
HPV #'s assoc w/warty, flat lesions which can progress to malignancy
16, 18, 31, 45
__ and __ are the principle transforming genes of HPV
E6, E7
HPV E6 binds to ____ ; degrading it --> so cells are allowed to progress from ___ to ___ in the cell cycle and chromosomal damage doesn't stop cell growth
p53, G0/G1, S
HPV E7 binds to ___ . As a result ____ cannot be inactivated; w/this TF unchecked, DNA synth (S phase) of cell cycle promoted
Rb, E2F
HPV induces hyperplasia of ____ layer of epithelium
basal
HPV viral DNA does what?
Integrates into cell genome -disrupts reg actions of host genes
what anchors the breast to the dermis?
Suspensory ligaments of Cooper (fibrous septa)
division of breast starting from nipple
nipple-->lactiferous sinus-->lacterifous duct which bifurcates successively
until terminal bifurcation-->lobule; each breast has 5-10 radially arranged lobes (each lobe has 1 lact duct and many lobules)
Acini are referred to as _____ when not pregnant, and ___ when one is.
rudimentary, true
functional unit of the breast
terminal ductal lobular unit (TDLU) = ductules, rudimentary acini, surrounding a terminal duct
intralobular CT can be found _____
surrounding each lobule
interlobular CT can be found ____
between each lobule
intralobular vs. interlobular CT
loose, myxomatous (intralobular) vs. dense, fibrous (interlobular)
Name 2 lesions of LOBULAR stroma
1) Fibroadenoma
2) Phyllodes tumor
the deep dorsal limit of the breast
anterior pectoral fascia
estrogen acts on the _____ of the breast to promote ______
duct epithelium; growth
progesterone acts on the _____ of the breast to produce _____/____
TDLU epithelium, secretory change/stromal edema
follicular phase - breast is _____
quiescent (epith undergoes apoptosis, lobules atrophy, edema decreases)
luteal phase - breast cells _____
actively proliferate, lobular hyperplasia, stromal edema
swelling and discomfort in breasts before menses is caused by this
stromal edema
Why is it recommended to do Breast self-exam 1 wk after menses?
b/c no stromal edema, breast nodularity at its lowest
hallmark of perinatal breast development
lactiferous ducts only
at 6 wks gestation, breast development
primary bud (epidermis into dermis)
at 12 wks gestation, breast development
secondary bud
breast development from 12 wks to birth
development of mammary pit in secondary bud (w/areola and depressed nipple), lactiferous ducts develop
breast development in infant and childhood
more branching ducts (male breast arrests at pre-pubertal phase)
pubertal breast development
complex branching ducts, terminal ducts/saccules, stromal proliferation
menarche breast development
saccules --> terminal ductules, rudimentary acini, TDLU
gestational/lactating breast
true secretory gland, fully developed breast
post lactation breast
epith atrophy, some fatty replacement of stroma
postmenopausal breast
stromal and glandular atrophy, fatty replacement
what is commonly seen on the milk line?
accessory breast tissue (also common in axilla) or supernumerary nipple (esp below breast)
atypical ductal hyperplasia (ADH) = ?
some but not all the features of DCIS (can't differentiate ADH from well diff DCIS)
histopath features of atypical ductal hyperplasia (high grade)
monotonous nuclei, fried egg appearance of cells, prominent intracytoplasmic vacuoles, a few signet ring cell forms
Sx: varying sized irregular masses in both breasts, painful mass in one breast (needed excision), told "no cancer"
Name the breast condition:
fibrocystic changes
Sx: intermittent brownish nipple discharge for 5 wks, small palpable mass below nipple
DDx for breast dz:
1) Papilloma
2) Papillary Carcinoma (inv vs. non-inv)
3) Pagets (poss but usually no mass)
T or F? Pagets dz of nipple is often associated w/ a mass
False
Papilloma vs. Papillary carcinoma differences (breast)
malignant dz - lacks myoepithelial layer, has delicate vascular stroma and solid/cribiform areas w/high mitoses); benign - fibrovascular cores; 2 layer epith
most common part of breast to have carcinoma found
UOQ
Sx: freely movable mass in 1 breast (young woman)
Name of Breast condition:
fibroadenoma
Histopath features of fibroadenoma
biphasic (epith/glandular and stromal) neoplasm; ducts - small and round (pericanalicular pattern) or long and C-shaped (intra-canalicular pattern); no atypia; mitoses absent/few
histopath features of phyllodes tumor
gland architecture complex, stroma very cellular - some stellate (atypical) w/mitoses present; higher risk for recurrence and malignant potential;
What alarming feature can be seen in fibrocystic change?
sclerosing adenosis (nests of hyperplastic cells - proliferation of small ducts)
What proportion of women who get breast ca have known RFs?
3/10
BRCA1
17q mutation of tumor suppressor gene; 85% lifetime risk of breast ca, 20-50% ov ca;
Carriers of BRCA1 (similar BRCA2)
50% of breast ca families, 90% breast/ov ca families, 3% Jewish women (25% if Jewish women who get breast ca before 42 have it)

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