Week 2 Flashcards
Oocyte
germ cell 4N, undergoes meiosis I and II to form mature oogonia
Oogenesis:
what happens in Meiosis I? When does this occur?
4N primary oocyte → undergoes Meiosis I (recombination, DNA exchange between non-sister chromatids) → Primary Oocyte (4N)
Occurs during fetal life, arrests at prophase of meiosis I
Oogenesis:
when does Meiosis I resume?
what do you have at the end of meiosis I?
Meiosis I does not resume until LH surge just before ovulation
→ 2N, haploid SECONDARY OOCYTE (ovulated) + polar body 1 (2N)
Secondary oocyte
2N, haploid
Secondary oocyte arrested in meiosis II until fertilization
If unfertilized, ovulated secondary oocyte degenerates
Primary Oocyte
4N, diploid
arrested at prophase of meiosis I until ovulation
Oogenesis:
Meiosis II
when does it occur?
what do you have at the end?
doesn’t occur until fertilization
2N oocyte → fertilized oocyte (1N, haploid) + 2nd polar body (1N)
The menstrual cycle:
Lasts _____ days
2 main phases and their duration?
28 days
Follicular Phase: proliferative, day 1-14
Luteal Phase: secretory (day 15-28)
What phase of the menstrual cycle is more variable - Follicular or Luteal?
Follicular - length can vary
Luteal - Most consistent duration, always precedes onset of menses by 14 days
4 main steps of follicular phase of menstrual cycle
1) Development of follicle
2) Upregulation of LH/FSH receptors on Theca/Granulosa cells → increased sensitivity to LH/FSH
3) Estradiol levels increase –> proliferation of endometrium
4) Ovulation: day 14
Follicular growth is fastest during the _____ week of the follicular phase
2nd
What is estradiol doing during the earlier parts of the follicular phase?
what are the levels of FSH, LH, and progesterone?
FSH/LH suppressed by negative feedback of estradiol
**Progesterone, FSH, and LH levels LOW during follicular phase
Cervical mucus consistency during follicular vs. luteal phase
Follicular: High estrogen → thin, watery, cervical mucus
Luteal: High levels of progesterone → Thick, viscous cervical mucus, impenetrable by sperm
Ovulation
day 14
Estrogen levels rise throughout follicular phase → peaks → REVERSAL of negative feedback → POSITIVE FEEDBACK → LH surge
Estrogen levels decrease just after ovulation, then rise again during luteal phase
Luteal phase main steps (2)
1) After egg is ovulated → follicle becomes corpus luteum → progesterone
2) High levels of progesterone- -> Proliferation of tortuous spiral arteries and glandular secretions from endometrial lining (prepare endometrium for fertilized egg) AND Increase basal body temperature
What happens at the end of the luteal phase if fertilization does NOT occur
Corpus luteum regresses → estrogen/progesterone levels decrease abruptly → shed endometrial lining
What happens at the end of the luteal phase if fertilization DOES occur
hCG and progesterone from corpus luteum maintains endometrial lining
Primordial Follicle
Oogonia + somatic (PRE granulosa) cells
Oocyte arrested at prophase of Meiosis I in primordial follicle
Present by 6 months of life
Primary Follicle = _______ + ________ + _________ under the basement membrane
primary oocyte + zona pellucida + single layer of cuboidal granulosa cells under BM
Zona pellucida
glycoprotein coat surrounding primary oocyte, facilitates sperm attachment and fertilization
Secondary Follicle = _______ + ________ + _________ under the basement membrane
Primary oocyte + Zona Pellucida + several layers of cuboidal granulosa cells + BM
Preantral follicles (3)
1) Primordial follicle
2) Primary follicle
3) Secondary follicle
Antral follicles (2)
1) Tertiary Follicle
2) Graafian follicle
Tertiary follicle = _______ + ________ + _________ under the basement membrane + _______ and _________ outside the BM
primary oocyte + zona pellucida + granulosa cell layers + BM + Theca interna/Theca externa
Meiotic division which gives rise to secondary oocyte occurs in _______ follicle just before _______
Meiotic division which gives rise to secondary oocyte occurs in graafian follicle just before ovulation
Corpus Luteum
remnant of ovulated ovarian follicle, no oocyte present
Highly vascular → LH/FSH stimulate progesterone/estrogen secretion
Produces high levels of progesterone which supports pregnancy
Corpus Luteum if fertilization does NOT occur
No fertilization → CL degenerates (becomes fibrosed) 11 days after ovulation (Corpus Albicans)
Corpus Luteum if fertilization DOES occur
Conception and ongoing pregnancy occur →
-Remaining cells of ovulated follicle become corpus luteum
Placental production of hCG (a-subunit similar to LH) stabilizes corpus luteum and thus progesterone production for first 9 weeks until placenta able to make progesterone independently
Regresses after first few weeks → Corpus Albicans
Large growing follicles containing eggs are needed to produce _______
estradiol
Local autocrine/paracrine factors influencing follicular matruation
Interleukins, growth factors (VEGF → increase blood flow to developing follicles)
-Activin
–Inhibin
Activin autocrine/paracrine effects
augments FSH, suppresses androgen production in theca cells (increases estrogen)
Inhibin autocrine/paracrine effects
later in follicular phase, enhances LH stimulation of androgen synthesis in theca cells → more substrate for estrogen synthesis in granulosa cell → LH surge
Dominant follicle
single follicle that ovulates each cycle
Determined by local hormonal milieu (more estrogen, better blood supply, more FSH receptors, more granulosa cell proliferation, more aromatase activity, more inhibin)
2-Cell Theory of Sex Steroid Production
TWO cell types needed to produce estradiol
Theca → produce androgens that are taken up by Granulosa cells
Granulosa cells → convert androgen → estradiol
Layers of Endometrium
1) Stratum basalis
2) Stratum Functionalis (Stratum spongiosum + Stratum Compactum) –> shed during menstruation
Stratum basalis
deepest layer, adjacent to myometrium, does not change appreciably during menstrual cycle
Permanent stromal tissue
Contains endometrial glands
Basal layer that regenerates stratum functionalis each cycle
Stratum spongiosum
thick intermediate layer between basalis and compactum
part of stratum funcitonalis
Stratum Compactum
superficial layer of endometrium
part of stratum funcitonalis
Spiral arteries
pass through basal layer into stratum functionalis
Hormonally sensitive
Constrict in response to hormonal shifts → stratum functionalis becomes ischemic → sheds
Straight arteries
feed stromal layer of endometrium
Do NOT infiltrate endometrium very deeply
Endometrial Phases: (3)
1) Menstrual phase
2) Secretory phase
3) Proliferative phase
Menstrual Phase
lasts 5 days = Menses
Endometrial ischemia (spiral artery constriction) → shedding of stratum functionalis → menstrual effluvium (blood, necrotic epithelium, necrotic stroma, inflammatory cells, fibrin deposits)
Corpus luteum degenerates → fall in progesterone/estrogen
Secretory Phase
in response to high progesterone (secreted by corpus luteum)
Endometrial glands become more tortuous and secrete glycogen rich substance capable of sustaining conceptus before placenta forms
Endometrial stroma becomes increasingly edematous
Proliferative Phase:
in response to ovarian estrogen
Endometrial stroma proliferates, becomes thicker/highly vascular
Tubular glands of stratum compactum invaginate, elongate, and become more coiled
Cryptorchidism
Undescended testis (Unilateral or bilateral)
Impaired spermatogenesis due to increased intra-abdominal temperature
-increased risk of germ cell tumors in undescended testis AND contralateral side
- Atrophy evident as early as age 2
- Contralateral testis may also regress
Varicocele
Dilated veins in pampiniform plexus due to increased venous pressure
Due to venous valve insufficiency
Typically LEFT side (or bilateral in 10%) due to increased resistance to flow from L gonadal vein –> L renal vein
-Can cause infertility (increased temperature)
“bag of worms” on palpation
does NOT transilluminate
cryptochidism
-what lab values?
- LOW INHIBIN, INCREASED FSH and LH
- TESTOSTERONE: low in bilateral, normal in unilateral
Normal testosterone because Leydig Cells unaffected by temperature
Nonspecific Epididymitis/Orchitis
destruction, necrosis, and abscess formation
Due to urinary tract infection
Causes of Epididymitis/Orchitis in children vs. sexually active adults vs. elderly
Children - associated with urinary tract malformation (gram neg rods)
Sexually active adults - C. trachomatis, N. gonorrhoeae
Elderly - Enterobacteria
Mumps orchitis
atrophy due to blood supply restriction
Pubertal or adult males
1 week after parotid swelling
Unilateral in most cases (70%)
Infertility uncommon
Tuberculous orchitis
-what does it effect first - epididymus or testis?
Effects epididymis → then testis
Usually part of systemic disease
Formation of caseating granulomas
Syphilis inflammatory disease of the testes
-what does it effect first - epididymus or testis? why?
Effects testis → then epididymis (effect inner part of testi first due to obliterative endarteritis)
Congenital or acquired
Plasma cells, lymphocytes present
Obliterative endarteritis
Gummas
Inflammatory disease of the testes: (4)
1) Nonspecific Epididymitis/Orchitis
2) Mumps orchitis
3) Tuberculous orchitis
4) Syphilis
Hydrocele
Fluid collection within the tunica vaginalis (serous membrane covering testicle and internal surface of scrotum)
Associated with incomplete closure of processus vaginalis leading to communication with the peritoneal cavity (infants) or blockage of lymphatic drainage (adults)
TRANSILLUMINATED scrotal swelling
Testicular Germ Cell Tumors (6)
1) Seminoma
2) Spermatocytic seminoma
Non-seminoma:
3) Yolk sac (endodermal sinus) tumor
4) Choriocarcinoma
5) Teratoma
6) Embryonal Carcinoma
6) Mixed
Testicular Germ Cell Tumors
> 95% of testicular tumors
Pure or mixed (germ cell is pluripotent - tumor is pluripotent)
Metastases can vary from primary
Tends to occur in young men (15-30 yrs)
PAINLESS testicular enlargement
Testicular Germ Cell Tumors:
Predisposing factors?
Cryptorchidism
genetic factors
dysgenesis
chromosomal changes (Kleinfelter)
Seminoma
response to chemo?
serum markers?
frequency?
can produce what?
Most common testicular tumor (50%)
Radiosensitive and chemosensitive - good prognosis
Serum markers negative
In rare cases, may produce hCG
Seminoma
appearance?
LARGE cells + CLEAR cytoplasm + CENTRAL nuclei –> resemble SPERMATOGONIA
hematogenous mass with NO hemorrhage or necrosis
Embryonal carcinoma
appearance
IMMATURE, PRIMITIVE cells that may produce GLANDS
forms HEMORRHAGIC MASS with NECROSIS
Embryonal carcinoma
response to chemo?
aggressive or not?
age effected?
Chemosensitive - BUT chemo may result in differentiation into another type of germ cell tumor**
Aggressive, with early hematogenous spread
Presents in 30’s
Embryonal carcinoma
serum markers?
May also have increased _____ or ______
PLAP, placental lactogen, hCG
May also have increased AFP or B-hCG
Yolk sac (endodermal sinus) tumor
appearance?
Malignant tumor that resembles yolk sac elements
Schiller-Duval Bodies (glomerulus-like structures) are seen on histology
Yolk sac (endodermal sinus) tumor
- most common tumor in who?
- what is usually elevated?
- Prognosis
Most common testicular tumor in CHILDREN
alpha-fetoprotein (AFP) elevated
Prognosis relatively good
Choriocarcinoma
appearance?
Malignant tumor of syncytiotrophoblasts and cytotrophoblasts (placenta-like tissue, but villi are absent)
Choriocarcinoma
Spreads early in BLOOD
B-hCG characteristically elevated –> can lead to hypothyroidism or gynecomastia (a-subunit of hCG similar to FSH, LH, and TSH)
Very rare, and aggressive with high rate of mets
Teratoma
appearance?
tumor composed of mature fetal tissue derived from 2-3 embryonic layers
Teratoma is benign in females, but MALIGNANT in males
Teratoma
Malignant transformation is common (any component can transform)
Chemoresistant - slow to progress, but may undergo malignant change
Mixed germ cell tumors
Germ cell tumors are usually mixed
Prognosis is based on the worst component
Sex cord / Stromal Tumors in Males
Usually benign
1) Leydig cell tumor
2) Sertoli cell tumor
Leydig cell tumor
usually produces androgen –> causes precocious puberty in children, gynecomastia in adults
Sertoli cell tumor
Comprised of tubules and is usually clinically silent
Condyloma Acuminatum
Benign warty growth on genital skin
Due to HPV 6 or 11
Characterized by koilocytic change
Lymphogranuloma venereum
Necrotizing granulomatous inflammation of the inguinal lymphatics and lymph nodes
Sezually transmitted disease caused by Chalmydia trachomatis (serotypes L1-L3)
Eventually heals with fibrosis
Perianal involvement may result in rectal stricture
Carcinoma in situ of the penis
plaque-like lesions, full thickness dysplasia replacing full thickness of squamous cells
precursor to squamous cell carcinoma
Bowen’s disease
Carcinoma in situ of the penile shaft or scrotum that presents as LEUKOPLAKIA
Erythroplasia of Queyrat
Carcinoma in situ of the GLANS that presents as ERYTHROPLAKIA
Bowenoid papulosis
Carcinoma in situ of the penis that presents as multiple reddish papules
seen in younger patients (40s) relative to Bowen disease and erythroplasia of Queyrat
Does NOT progress to invasive carcinoma
Squamous cell carcinoma of the penis
Malignant proliferation of squamous cells of penile skin
Typically in patients 60-80 years of age
Ulcerating rolled up lesion, highly destructive
Precursor lesion: carcinoma in situ
Risk factors for Squamous cell carcinoma of the penis
High risk HPV (2/3 of cases)
Lack of circumcision - foreskin acts as nidus for inflammation and irritation ir not properly maintained
Prostate anatomy:
__________ zone surrounds the urethra
__________ zone surrounds the ejaculatory duct that empties into prostatic urethra
________ zone is in the outer regions of the prostate
Transition zone
Central zone
Peripheral zone
________ zone is where prostate cancer typically arises
___________ zone is where Benign Prostatic Hyperplasia usually occurs
Peripheral zone = cancer
Transition zone = BPH
Acute Prostatitis
Acute inflammation of the prostate, usually due to bacteria
Presents with dysuria, fever, chills
Prostate is tender and boggy on digital rectal exam
Prostatic secretions show WBCs, culture reveals bacteria
pus filled, focal or diffuse polymorphonuclear inflammation
Acute Prostatitis causes in young adults vs. older adults
- Chalmydia, N. gonorrhoeae in young adults
- E. Coli, Pseudomonas in older adults
Can be iatrogenic due to catheter insertion
Chronic Prostatitis
Chronic inflammation of the prostate
presents as pelvic or low back pain
Prostatic secretions show WBCs, but cultures are NEGATIVE
Mononuclear cell inflammation
Often associated with atrophy
Typically asymptomatic
Unclear etiology
Benign Prostatic Hyperplasia (BPH)
hyperplasia of prostatic stroma and glands (typically in transition zone - central periuretheral zone of prostate)
Age-related change
NO INCREASED RISK for cancer
Blacks > whites > Asians
Pathophysiology of BPH
Related to DHT:
- T –> DHT via 5a-reductase
- DHT acts on androgen receptor of stromal and epithelial cells resulting in hyperplastic nodule
Clinical features of BPH
1) Problems starting and stopping urine stream
2) Impaired bladder emptying with increased risk of infection and hydronephrosis
3) Dribbling
4) Hypertrophy ofbladder wall smooth muscle (increased risk for bladder diverticula)
5) Microscopic hematuria
6) PSA may be slightly elevated (<10) due to increased number of glands
Treatment of BPH (4)
1) a1-antagonists (terazosin) –> relax smooth muscle (can also lower BP)
2) Selective a 1A-antagonists (temulosin) –> can be used in normotensive individuals to avoid a1B effects on blood vessels
3) 5a-reductase inhibitor –> block formation of DHT, takes months for results, can also treat male pattern baldness
4) TURP
Adenocarcinoma of the prostate
epidemiology
Most common non-skin cancer of adult males
Second leading cause of male cancer death, > 200,000 new cases per year, > 27,000 deaths per year
More men die WITH PCa than of it
Main risk factors = age, race (black > white > asian), and diet (high saturated fat)
Adenocarcinoma of the prostate
Malignant proliferation of prostatic glands
Usually clinically silent
-arises in PERIPHERAL and POSTERIOR region of prostate –> no urinary sx
Prostate cancer screening
Begin at age 50 with DRE and PSA
PSA –> increases with age due to BPH
-PSA > 10 –> highly worrisome
Decreased % free PSA is suggestive of cancer because cancer makes bound PSA
Prostatic biopsy used to confirm presence of carcinoma = GOLD STANDARD
Adenocarcinoma of the prostate
Appearance
Small, invasive, glands with prominent (large) nucleoli
Infiltrative pattern
Single cell layer (loss of basal cells)
Perineural invasian
How and where does prostate cancer spread?
Lymphatically AND hematogenously to axial skeleton (spine or pelvis)
Presents as low back pain and increased ALK PHOS, PSA, and prostatic acid phosphatase (PAP)
Gleason grading system
based on ARCHITECTURE ALONE (NOT NUCLEAR ATYPIA)
Multiple regions of tumor assessed because architecture varies from area to area
Score (1-5) assigned for two distinct areas then added to produce final score (2-10) –> higher is worse prognosis
Treatment of Prostate cancer
Prostatectomy (localized disease)
Hormone suppression (reduce T and DHT) –> Leuprolide (GnRH analog), or Flutamide (androgen receptor inhibitor)
Prostatic intraepithelial neoplasia
Can be noninvasive precursor to some prostate cancers (30-50% of prostates with PIN harbor prostate cancer)
Genetic and molecular changes similar to PCa
Frequency increases with age
