Female Pathophys Flashcards
Follicle development in female menstrual cycle?
- Birth: 2 million primordial follicles
-
Puberty: 500,000 primordial follicles
- (rest were defective and got rid of)
-
Every month: 2 dozen primordial follicles start to develop→ healthiest one continues to develop and suppresses the rest of developing follicles
- Primordial follicle: Granulosa precursors = Squamous cells
- Very large cell
- Primary Follicle:
- Oocyte (salmon color)
- Nucleus (green)
-
Granulosa cells
- Cuboidal
- Columnar
- Secondary Follicle:
- Multiple layers (3)
- Granulosa cells (closest to Oocyte)
- Theca Interna
- Theca Externa (Theca cells)
- Multiple layers (3)
- Graafian Follicle (Mature Follicle)
- “Follicle of the month” → rupture → releasing egg (sometimes multiple eggs)
- Cytoplasm of Oocyte (small salmon circle)
- Nucleus (green)
- Antrum
- Filled with fluid
- Primordial follicle: Granulosa precursors = Squamous cells
-
Mid-cycle: Follicle ruptures → releasing egg (oocyte/ovum) into pelvis
- Converts to Corpus Luteum (Lut= Yellow body)
- Produces: Progesterone (primarily)
- ~2 weeks
- No implantation → Corpus albicans (scar tissue) → cycle starts over again
- Converts to Corpus Luteum (Lut= Yellow body)
Layers of the antral follicle? ROLES?
- Before mid-cylce: Egg would be against granulosa cell/layer
- Mid-cycle/slightly before: Antrum starts forming
- Egg sitting in “pedestal” - (zona pellucida??)
- More internal than before
- Egg surrounded by granulosa cells (Cumulus oophorus)
- Most granulosa cells are bordering antrum
Theca Interna- “white speckles”
- Makes cholesterol → convert into Androgens!!
- Androgens made: Testosterone and Androstenedione
- *lipid soluble (diffuse through membranes into plasma membrane) → into granulosa cells/layer → converts androgens → estrogens
- Estrogen concentration at Antrum/ “what would have been the egg → HIGH
- ESTROGEN CONCENTRATION IN FOLLICLE HIGHEST compared to body
Theca Externa
- Epithelial “coating” (like CT)
- Doesn’t do anything important
Photomicrograph of a small part of the wall of an antral follicle, showing the antrum, the layer of granulosa cells, and the thecas. The theca interna surrounds the follicle, and its cells appear lightly stained because their cytoplasm contains lipid droplets, a characteristic of steroid-producing cells. The theca interna is surrounded by the theca externa, which merges with the stroma of the ovary. A basement membrane separates the granulosa layer from the theca interna. PT stain. High magnification.
Female HPA axis to thecal cells and granulosa cells?
Hypothalamus → GnRH (Gonadotropin-releasing Hormone) → Anterior Pituitary → LH and FSH
- LH: Androgen Synthesis
- Stimulates Theca interna cells → Androgen synthesis
- Produce: (Androgens)
- Testosterone
- Androstenedione
- Steriods → diffuse across BM/plasma membranes into granulosa cells
- FSH: Androgen conversation into Estrogen
- Stimulates granulosa cells → Aromatase enzyme
- Aromatase + Androgens → Estrogens
- Estrogen [] high in granulosa cell/follicle→ stimulates egg
- Mid-cycle → stimulates follicle to rupture
First step in amenorrhea flowchart?
No period
Positive Pregnancy Test
- Pregnant or lactation -or-
- Trophoblastic tumor- cells produce HCG
- Chorionic cells of placenta that normally produce HCG during pregnancy
- Cancerous or Precancerous
- Chorionic cells of placenta that normally produce HCG during pregnancy
Negative Pregnancy Test
- Primary Amenorrhea- no MC ever
- Secondary Amenorrhea- previously had MC and now don’t
-
Then check Serum Prolactin
- stimulates milk production
- Suppresses ovulation/MC (not completely inhibit) → can still get pregnant if BF if prolactin levels high (vice versa)
-
Then check Serum Prolactin
What are causes for prolactin levels to be high causing amenorrhea?
Prolactin (Hyperprolactinemia)
-
*Hypothalamic tumor: Prolactin secreting tumor in anterior pituitary (most common of hormone secreting hormones) (can also be idopathic and drugs but less common)
- Dx: CT/MRI of sella turcica
- Pituitary lesion
-
CNS influences (if no pituitary lesion): secretes prolactin to inhibit menses
- Stressed: body secretes prolactin to protect itself against getting pregnant.
- Starvation
-
Excessive exercise:
- Body fat < 10% → menstruation becomes erratic
- Body fat < 9% → menstruation shut off
What if prolactin is normal when checked d/t amenorrhea?
-
Check TSH. IF HIGH… (Normal = 0.3-5mU/l or SI)
- TSH high → T3/T4 decrease→ Hypothyroidism → Amenorrhea
- Normal TSH → Progesterone Challenge
-
If TSH normal–> Progesterone Challenge
- Progesterone: Stimulates endometrium to grow
- Give progesterone ~2 weeks then stop → endometrium will slough off (menses)
- Stimulates normal cycle
- ex: Corpus luteum → corpus albicans (FSH and LH decrease end-cycle) → no progesterone → endometrium slough off → menses)
- Withdrawal bleeding = Anovulation
- Everything working but ovarian cycle
- No bleeding → Estrogen challenge
What is the estrogen challenge in amenorrhea flowchart?
Estrogen with Progestin challenge (birth control pills)
- Birth control pills = Estrogen & Progesterone
- Placebo pill week → no estrogen and progesterone
- Withdrawing estrogen:
-
Withdrawal bleeding → check FSH/LH
-
Primary Ovarian Failure:increased FSH/LH
- Anterior Pituitary trying to recruit follicle but can’t find good one → Menopause
- Ex: ~65 yo → Regular menopause
- Ex: Young women w/o ever having MC → check karyotype (ex: Turner’s Syndrome)
-
Secondary Ovarian Failure: N/ decrease FSH/LH
- Pituitary tumor/lesion secreting Prolactin → ¯ levels of FSH/LH
-
Primary Ovarian Failure:increased FSH/LH
-
No bleeding → End organ problem
- End organ problem
- Ex: Problem in uterus or outflow tract clogged (cervix clogged or hymen intact)
- End organ problem
What is HCG similar to?
- LH
- TSH
- FSH
- all have the same alpha strand, but different beta strand
Relative structures of glycoprotein hormones. The three pituitary glycoprotein hormones (TSH, FSH, LH) and the placental glycoprotein (HCG) share a common α-subunit. Hormone specificity is conveyed by the β-subunit and the resulting three-dimensional protein structure. CHO indicates the approximate location of carbohydrate side chains. HCG differs from LH solely by having an additional 32 amino acids in its β-subunit. aa, amino acids.
Where is HCG made? What is the cycle of HCG production during pregnancy?
made from Chorion (cells like placenta)
Cycle of HCG production:
- Zygote implants (Blastocyst) → growing → produces Chorion (1st structure appears)
- Chorion- boundary between fetal and maternal development
- Chorion→ starts producing HCG (immediately-w/in ~2 days)
- HCG (looks like LH→ straight tail vs. curvy tail)
- ~1-2 days after implantation → HCG binds to LH receptor on corpus luteum
- End of cycle when LH falls (d/t AP) → HCG allows corpus luteum to fx → produces progesterone
- Progesterone: prevents endometrium from sloughing off → preventing menses
- ~1-2 days after implantation → HCG binds to LH receptor on corpus luteum
What does pregnancy test look for?
-
Looks for β-strand on HCG → different than other hormones
- Not looking at α-strand→ on all 3 hormones (would always be positive results)
How does HCG stimulate TSH?
- Binds to TSH receptors lower affinity d/t high [] of HCG during pregnancy
- During pregnancy: TSH levels DECREASE
-
Thyroid Function Assessment in Pregnancy: Essential!
-
T3/T4 LEVELS need to be assessed!!
- TSH levels not helpful in assessing function (cant factor in HCG binding)
-
T3/T4 → Crucial for brain development in fetus
- Dx: look at T3/T4 levels for pregnant pts
- Tx: administer synthetic thyroid hormone (Synthroid)
-
T3/T4 LEVELS need to be assessed!!
How does production of gonadotropes change in utero and few months after birth?
In Utero
- LH/FSH: increase levels
- M and F → develops sex organs
- Ex: decrease levels → no sex organs
- M: Testosterone and Androstenedione
- F: Estradiol
Few Months after Birth
- LH/FSH: increase levels → finish primary/secondary effects
How do gonadotropes change 6 months–> puberty and durign puberty?
6 months to Puberty
- LH/FSH: decrease levels (0)
- 6 yo boy vs. girl have no difference in secondary sex characteristics
Puberty
- Gonads → LH/FSH increase levels
- Males: deeper voice, facial hair
- LH/FSH levels increase until death
- Female: Breast development
- LH/FSH levels cycle up and down (Puberty → menopause)
- Progesterone & estrogen cycle (Puberty → menopause)
- Males: deeper voice, facial hair
What happens to gonadtrope production during menopause?
Running out of good eggs → increase LH/FSH each cycle to recruit last good eggs
- Menopause → LH/FSH increase significantly (last stitch effort that wont work)
- *Estrogen produced by follicle
Menopause: No follicles left→ estradiol levels decrease
- Progesterone & Estrogen: decrease levels (no good follicles to produce)
-
FSH/LH: increase levels
- Why: Still have GnRH from hypothalamus stimulating AP to make LH/FSH but NO follicles to convert to Estrogen and Progesterone
- Corpus Luteum (mid-cycle) = Progesterone
- Theca interna cells and granulosa cells (with LH/FSH) = conversion of androgens to Estrogen
- Why: Still have GnRH from hypothalamus stimulating AP to make LH/FSH but NO follicles to convert to Estrogen and Progesterone
Link between HPV and cerivcal cancer?
HPV: produce proteins that block RB and P53 protein
- Not a mutation
- Block actual proteins
Types:
- HPV 1 → plantar warts
- HPV 2 → hand/elbow/knee warts
- Sexually transmitted ones
- Low-risk HPV (6, 11) → Condyloma (genital warts)
-
High-risk HPV (16,18, others) → cervical cancer
- 2/3rd of all cervical cancers
HPV Virus → affects cells of cervix
- Antibodies → destroys cells that are infected with virus
- Attach to virus particle when going into another cell → destroy
- HPV exposure: Millions/yr (130 million)
-
CIN (Cervical Intraepithelial Neoplasia → (Persistent infection): 1 million
- Most women fight off without problem
-
High Grade CIN
- Block RB and P53 (tumor suppressor genes) → risk of mutations → risk of cancer mutations
- Invasive Cancer: 10,000/yr
- Metastasis: 5,000/yr
Annual number of cases worldwide of HPV induced cancers?
HPV is responsible for almost 100% of cervical cancer.
- Prevent HPV → prevent cervical Cancer
- HPV vaccines (not an “anticancer vaccine”) – Gardasil
- Works same as flu vaccine but prevents cancer
- Vaccinate women before exposure → builds immunity → exposure allows clearance of virus before infected → prevent cervical cancer
- Administered to boys as well
- R vs. B → better to administer since vaccine had low adverse effects
- HPV vaccines (not an “anticancer vaccine”) – Gardasil
- HPV is also responsible for cancers at other sites.
Various environments of uterus, vagina and cervix? Cell type? Things we want to prevent from entering, allow entering cervix?
-
Uterus: needs to be clean → Waiting for a zygote to implant
- Don’t want macrophages inside keeping it clean (like alveoli/liver)
- Not an immune privilege site and don’t want surveillance
- Ex: mistake zygote as bacteria → destroy before implantation
- Columnar epithelium cells
- Don’t want macrophages inside keeping it clean (like alveoli/liver)
-
Vagina: Exposed to external environment
- Pathogen latent (bacteria, fungus, protozoans)
- Do NOT want transmission of stuff from vagina to uterus
- Stratified Squamous Epithelium
-
Cervix: in between Vagina and Uterus to protect uterus
- Normally blocked
- 3 Things allowed for passage: (really 4)
- Menses
- Sperm
- Baby
- IUD → inserted through cervical canal and put inside uterus
* Removable with string that is hanging in vagina (to become pregnant)
* Dalkon shield (1970’s): w/ COTTON string- Cotton: wicks (absorbes) water
- Draws water out of vagina and into uterus → carried pathogens through!
- uterine infections → salapingitis → infertility
- IUD → inserted through cervical canal and put inside uterus
How do cell types change in uterus, vagina thorughout life cycle?
- Uterus= Columnar epithelium
Vagina= Stratified squamous epithelium
- Need something in between! → Squamocolumnar Junction
- At birth:
- Columnar epithelial: in canal
- Squamous columnar junction (higher up at exocervix)
- Squamous cell: runs into canal
- Young Adult: (puberty → 20’s)
- squamous columnar junction: extends out of canal and into vagina
- Transition/transformation zone
- squamous columnar junction: extends out of canal and into vagina
- Adult:
- Transformation zone: (Cervical Cancer form risk area)
- Over course of cycle → tissues change
- Columnar epithelium–> squamous cell–> columnar epithelium etc
- Transformation zone: (Cervical Cancer form risk area)
- At birth:
What is the transformation zone and its significance?
- Squamous (right)
- Columnar (left)
-
Transformation Zone (middle): combo of squaous cell & columnar epithelium. Where cervical cancer is most likely to develop
- Different times of cycle will have difference cell types
- Why? Body wants to get pregnant
- During midcycle (most fertile time), plug (normally plugs cervical canal and prevents bacteria/virus into uterus) becomes unplugged → allows sperm to come in and fertilize
- Occurs for < 1 week/mo
- Cervical Cancer can be seen in pictures → see in TZ. If not visualized and possibly in canal → wait farther into cycle until out of canal
What are we looking for on pap smear?
Gardasil: protects from 2/3rd of HPV producing cervical cancers (still can get it with vaccine)
- Need pap smear → scrape cervical tissue and place under microscope
-
Cervical cancer under microscope = Large nuclei → rapidly replicating (hallmark of cancer)
- A: Normal
- B/C: Varying degrees of cancer
- CIN: Cancer in situ
- Cancer in place (no invasion)
What are leiomyomas?
Leiomyomas: Tumors of smooth muscle
- Leiomyomas (uterine fibroids) occur in 30-50% of women.
- They are not cancerous, and very rarely become cancerous.
- R pic: uterus with large benign tumors
- Asymptomatic to debilitating painful
- Risk factor: Postmenopausal
- Tx:
- Postmenopausal→ remove uterus
- Premenopausal → remove leiomyomas (well demarcated but little ones can eventually grow back)
A: Uterine section showing whorl-like appearance and locations of leiomyomas (uterine fibroids)
B: Multiple leiomyomas in sagittal section.
- Typical, well-circumscribed, solid, light gray nodules distort uterus.
What is uterine prolapse? Treatment?
Uterus outside of normal position–> Degrees of uterine prolapse.
A: Normal uterus.
B: First-degree prolapse
- Uterus descent within the vagina
- Vagina now 1/3rd normal length bc uterus occupying 2/3 of it
C: Second-degree prolapse
- Cervix protrudes through the introitus.
D: Third-degree prolapse
- Vagina completely everted (outside of body, inside-out)
- PAIN
Uterus→ held in place by ligaments and muscle
- Tx: Pelvic sling (hold uterus back)
What is a cystocele? Rectocele? What is POP?
Cystocele- Bladder prolapse through vagina
Rectocele- Rectum prolapse through vagina
PAINFUL
A: Cystocele
B: Large cystocele
C: Rectocele
D: Rectocele associated with ulceration of vaginal wall.
Pelvic organ prolapse (POP): (collective term)
- Uterine prolapse
- Cystocele
- Rectocele
- Tx and prevention: Kegel exercises and pelvic sling
What is salpingitis?
Salpingitis: Inflammation of fallopian tube and ovaries. Component of pelvic inflammatory disease
- Causes:
- Infection (common)
- (chlamydia, gonorrhea, tuberculous)
- Transvaginal/intravaginal US → increases risk of pushing infectious material up to fallopian tubes
- (chlamydia, gonorrhea, tuberculous)
- Endometriosis
- Endometrial tissue in fallopian tube
- Infection (common)
- Damage from Salpingitis → Results in scarring (infertilities and tubal pregnancy)
- Fallopian tubes: most common site for ectopic pregnancies (tubal pregnancy)
- Results in damage or destruction of tubes → can cause DEATH
- Fallopian tubes: most common site for ectopic pregnancies (tubal pregnancy)
A: Note the swollen fallopian tubes.
B: Ovary involvement common: Bilateral, retort-shaped, swollen, sealed tubes and adhesions of ovaries are typical of salpingitis.
What is pelvic inflammatory disease?
A: Involvement of both ovaries and fallopian tubes.
*Hard to palpate individually
B: Total abdominal hysterectomy and bilateral salpingo-oophorectomy specimen showing unilateral pyosalpinx
Ovarian Tumors? What type is most common? MOrtality rate?
Surface Epithelial Cells- most common cause
- Malignant ovarian tumors: 90%
- Age affected: 20+ yo
- Mortality rate: very high
- Ovaries small (peanut) and deep → cant palpate if grows in size
- Point of palpation → probably metastasized (late)
- Common detection at Stage 4 L
- Detect with US for early stages (false positives if screenings done)
Pic has other types of ovarian tumors… unsure if we need to know…
Prognosis and risk factors for ovarian cancer?
-
Prognosis: Poor
- ~23,000 cases/year
- ~14,000 deaths
- 5th leading cause of cancer death among women in the US.
- ~90% of ovarian cancers are from surface epithelial cells.
-
Risk factors:
- BRCA1 mutation- lifetime risk of ~30%
- Breast and ovarian cancer screenings → worth it!
- No mutation (“normal women”) → ~2% risk
- BRCA1 mutation- lifetime risk of ~30%
Large malignant ovarian tumor and metastasis of ovarian cancer.
A: Tumor has caused massive abdominal distention.
B: Pattern of spread for epithelial cancer of the ovary.
What is a teratoma?
“Tera”- monster
“oma”- swelling/tumor
- Opened mature cystic teratoma (dermoid cyst) of the ovary
- A ball of hair (bottom) and a mixture of tissues are evident
- Mature teratomas arise from germ cells and are seldom malignant
- Oogonia precursor cell (going to become gametes) → can give rise to any cell type in the body
- Differentiate to bone, skin, hair, eye, thyroid, muscle cell types, etc
- Typically develop in midline of body
- Form in utero
- NOT cancerous → do not become cancerous
- CAN have endocrine or ovarian function etc → remove
- Oogonia precursor cell (going to become gametes) → can give rise to any cell type in the body
What is placenta previa?
Placenta is too close to the (internal) cervical os (opening on uterine side)
- Complete (Total)
- Partial
- Marginal
- Low lying
Symptom: Painless vaginal bleeding
- Can causes significant bleeding at parturition
- Generally not a big problem
- ~1% of pregnancies
What is placenta acreta? increat? percreta? Consequences?
“How tightly placenta bound to uterus”
Normal: placenta only bound to Endometrium
With these…Placenta is embedded too deeply in uterus
-
Placenta accreta – attaches to myometrium (barely)
- ~stop bleeding with pressure
-
Placenta increta – invades myometrium
- When placenta out → pulls large piece of myometrium
-
Placenta percreta – reaches serosa
- Pulls chunk of uterus with it! → HEMORRHAGE
- ~hysterectomy
- Pulls chunk of uterus with it! → HEMORRHAGE
Consequences:
- Serious medical problem during delivery – removing the placenta will cause hemorrhage
- Often requires hysterectomy
What is abruptio placenta?
-
Premature detachment of the placenta
- Placenta nowhere near cervical os
- Placenta bound very tight to uterine wall → rupture PAIN
- Types:
- Partial- fetus still has blood supply (either concealed or apparent hemorrhage)
- Complete- EMERGENCY
- Fetus has NO blood supply and PAIN
- Symptoms:
- Painful
- Usually vaginal bleeding (not always)
- Concealed hemorrhage (L) → no visual vaginal bleeding but still hemorrhage
- Obstetric emergency – significant risk to fetus and mom
- Need baby out
- Can cause maternal shock, renal failure, coagulopathies
Postpartum hemorrhage? Treatment?
- Excessive bleeding after parturition
- Contraction of the uterus decreases blood flow and allows clotting
-
Obstetric emergency
- > 10% of all maternal deaths (USA)
- > 50% maternal deaths (worldwide)
*just know tx → STOP BLEEDING (don’t need txmt for exam)
- Tone: Soft “boggy” uterus
- Apply pressure
- Oxytocin- uterine contraction
- Trauma
- Laceration
- Inversion
- Tissue:
- Retained placenta
- Thrombin
- Blood not clotting
Amniotic fluid embolism? occurence? Complications?
- Amniotic fluid = interstitial fluid
- Contains epithelial cells (GI, Renal, Skin/Hair cells)
- Epithelial cells → contains TF (surface on epithelial cells)
- TF → maternal circulation → trigger coagulation → DIC
- Amniotic embolism is when amniotic fluid (w/ TF) enters maternal circulation → trigger coagulation → DIC
- Fetal cells trigger coagulation in maternal circulation
-
Complications:
- 1st. Pulmonary embolism
- Hypotension
- Fetal destress (¯ O2/BF to baby)
- ARDS ~93%
- Pulmonary edema → Cardiopulmonary arrest ~87%
- Progress to DIC if patient survives long enough
- Most survivors have long-term neurological disorders (from micro-clots to brain from DIC)
- 1st. Pulmonary embolism
- Rare
- ~1 per 20,000 births
- but ~10% of all maternal deaths
- Life threatening for mom & baby
- ~1 per 20,000 births
