Transcript Document 7224762

Chase Findley, MSIV
Gonadal Drainage, 454

Venous
 Left ovary/testis, left gonadal vein, left renal
vein, IVC

Lymphatic
Ovaries/testes,
para-aortic
lymph nodes
Derivation of Sperm Parts, 455

Acrosome
 Golgi apparatus

Neck
 Contains mitochondria
 Utilizes fructose

Tail (flagellum)
 Centrioles
Autonomic Innervation of Male
Sexual Response, 455

Erection
 Parasympathetic, pelvic nerve
 Nitrous oxide, smooth muscle relaxation,
vasodilation, erection

Emission
 Sympathetic, hypogastric nerve

Ejaculation
 Visceral, somatic, pudendal nerve
Male Reproductive Anatomy, 455
Semiferous Tubules, 456

Spermatagonia (germ cells)
 Maintain germ pool, produce primary
spermatocytes

Sertoli cells
 Secrete inhibin, inhibits FSH
 Secrete androgen-binding protein
○ Maintains local testosterone levels
 Forms blood-testis barrier
○ Isolates gametes from autoimmune attack
 Regulate spermatogenesis

Sertoli cells
 Secrete testosterone
Regulation of Spermatogenesis,
457

GnRH
 From hypothalamus,
stimulates FSH, LH
release from
pituitary

LH
 Stimulates Leydig
cells to synthesize
testosterone

FSH
 Stimulates Sertoli
cells to create sperm
Androgens, 458
Testosterone, DHT (testis)
 Andostenedione (adrenal gland)
 Testosterone function

 Differentiation of epididymis, vas deferens,
seminal vesicles
 Increase muscle, growth spurt, size of penis,
libido, spermatogensis
 Close epiphyseal plates (via estrogen)
 Deepen voice
Androgens, 458

DHT function
 Differentiate penis, scrotum, prostate
 Balding
 Increased sebaceous gland actitivity
 Prostate growth
Androgens, 458

Potency
 DHT>testosterone>androstenedione

5 α reductase
 Converts testosterone to DHT, inhibited by
finasteride

Aromatase
 Converts testosterone/androstenedione to
estrogen in adipose tissue and Sertoli cells
Estrogens, 458
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

17β estradiol (ovary)
Estriol (placenta)
Functions:
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Growth of follicle
Endometrial proliferation
Development of genitalia, breasts
Female fat distribution
Hepatic synthesis of transport proteins
Feedback inhibition of FSH/LH
LH surge
Myometrial excitability
Increase HDL, decrease LDL
Progesterone, 458


From corpus luteum, adrenal cortex, testes
Functions:
 Stimulate endometrial glandular secretions and
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spiral artery development
Maintenance of pregnancy
Decrease myometrial excitability
Production of thick cervical mucous, inhibits
sperm entry to uterus
Increase body temperature
Inhibit FSH/LH
Uterine smooth muscle relaxation, prevent
contractions
Menstrual Cycle, 459
Oogenesis, 460
Pregnancy, 460
Fertilization most commonly occurs in
upper fallopian tube, within 1 day of
ovulation
 Implantation in wall of uterus 6 days
after fertlization
 Trophoblasts secrete βHCG, detectable
in urine 1 week after conception

Pregnancy, 460

Lactation
 After labor, decrease in steroids induces
lactation
 Suckling maintains milk production by
increasing oxytocin and prolactin
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Prolactin
 Induces, maintains lactation, inhibits ovulation

Oxytocin
 Involved in milk letdown and uterine
contractions
hCG, 461

From synctiotrophoblast of placenta
 Maintains corpus luteum
○ Maintains progesterone production
○ Acts like LH, stimulates luteal cells
 Used as pregnancy marker, appears in urine
 Elevated in pathologic states
○ Hydatidiform moles, choriocarcinoma,
gestational trophoblastic tumors
Menopause, 461
Age related decline in ovarian follicles
 Decreased estrogen production

 Increased FSH/LH, GnRH
Symptoms include hot flashes, vaginal
atrophy, osteoporosis, coronary artery
disease
 Average age is 51

Klinefelter’s Syndrome, 461

XXY (male)
 Presence of inactivated X chromosome (Barr
body)
Testicular atrophy, eunuchoid body shape,
tall, long extremities, female hair
distribution
 Common cause of hypogonadism
 Dysgenesis of seminiferous tubules
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 Decreased inhibin, increased FSH
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Abnormal Leydig cell function
 Decreased testosterone, increased LH,
increased estrogen
Turner’s Syndrome, 461

XO (female)
 Short stature, ovarian dysgenesis (streak
ovary), webbing of neck, preductal
coarctation of aorta,
 Most common cause of primary amenorrhea
 Decreased estrogen
○ Increased LH and FSH
Sex Chromosome Disorders, 461
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Double Y males
 XYY (male)
 Phenotypically normal, normal fertility
 Tall, acne, antisocial behavior
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True hermaphroditism
 46,XX or 47,XXY
 Both ovary and testicular tissue present
 Ambiguous genitalia
Pseudohermaphroditism, 462
Disagreement between phenotypic and
gonadal sex
 Female (XX)

 Ovaries present
 External genitalia virilized or ambiguous
 Excessive of exposure to androgenic
steroids during gestation
 Caused by congenital adrenal hyperplasia or
exogenous administration of androgens
Pseudohermaphroditism, 462

Male (XY)
 Testes present, external genitalia feminized or
ambiguous
 Most common form is androgen insensitivity
○ Defect in androgen receptor
○ Normal appearing phenotypic female
○ Female external genitalia, rudimentary vagina
○ Internal genitalia absent (uterus, fallopian tubes)
○ Develop testes (internal), remove to prevent
malignancy
○ Increased sex hormones, LH
5α Reductase Deficiency, 462
Unable to convert testosterone to DHT
 Ambiguous genitalia until puberty

 Increased testosterone causes
masculinization of external genitalia
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Testosterone/estrogen levels normal
Abruptio Placentae, 463
Premature detachment of placenta
 Presents as painful bleeding in 3rd
trimester
 May be associated with DIC
 Increased risk with smoking,
hypertension, cocaine

Placenta Accreta, 463
Defective decidual layer
 Placenta attaches to myometrium
 Increased risk with prior c-section or
uterine inflammation
 Massive bleeding after
delivery

Placenta Previa, 463
Abnormal attachment of placenta to
lower uterine segment
 Presents as painless bleeding in any
trimester
 May occlude internal os
 Increased risk with
prior c-section
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Ectopic Pregnancy, 463
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Extrauterine implantation of pregnancy, most
often in fallopian tube
Presents as abdominal pain without bleeding
Increased risk with salpingitis
Suspect with increased hCG and sudden
lower abdominal pain, confirm
with ultrasound
Differentiate from appendicitis
Amniotic Fluid Abnormalities,
463

Polyhydramnios
 >1.5-2 L amniotic fluid
 Associated with esophageal/duodenal
atresia (inability to swallow amniotic fluid)
and anencephaly

Oligohydramnios
 <0.5 L amniotic fluid
 Associated with bilateral renal agenesis and
posterior urethral valves (inability to secrete
urine)
Cervical Pathology, 463

Dysplasia and carcinoma in situ
 Disordered epithelial growth
 Begins at basal layer of squamo-columnar
junction, extends outward
 CIN 1-3 depending on dysplasia
 Associated with HPV
16,18
 May progress to
invasive carcinoma
Cervical Pathology

Invasive carcinoma
 Often squamous cell carcinoma
 Pap smear used for early detection of
dysplasia (koilocytes)
 Lateral invasion can
block ureters, lead to
renal failure
Endometriosis, 464
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Non-neoplastic glands/stroma in abnormal
locations outside uterus
Cyclic menstrual bleeding from ectopic
tissue
Results in blood filled “chocolate cysts”
Presents as severe menstrual related pain
May cause infertility
Adenomyosis
 Endometrium within myometrium
Endometrial Proliferation, 464

Endometrial hyperplasia
 Endometrial gland proliferation caused by
increased estrogen stimulation
 Increased risk of endometrial carcinoma
 Presents as post-menopausal bleeding
 Risk factors include anovulatory cycles,
HRT, PCOS, granulosa cell tumor
Endometrial Proliferation, 464
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Endometrial carcinoma
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Most common gyn malignancy
Most common in 55-65 years
Presents as vaginal bleeding
Preceded by endometrial hyperplasia
Risk factors are unnopposed estrogen
therapy, obesity, diabetes, HTN, nulliparity,
late menopause
 Deeper myometrial invasion worsens
prognonsis
Myometrial Tumors, 464
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Leiomyoma
 Most common female tumor
 Benign, smooth muscle tumor, with rare
malignant transformation
 Multiple tumors with well demarcated
borders
 Most common in 20-40’s, blacks
 Estrogen sensitive
○ Increase in size with pregnancy, decrease
with menopause
Myometrial Tumors, 464

Leiomyoma
 May be asymptomatic or cause abnormal
uterine bleeding
○ May cause iron deficient anemia
 Whorled pattern of smooth muscle bundles
Myometrial Tumors, 464

Leiomyosarcoma
 Bulky, irregular shaped tumor
 Areas of necrosis, hemorrhage
 Highly aggressive, likely to recur
 Increased incidence in blacks
 May protrude from cervix
Premature Ovarian Failure, 464
Premature atresia of ovarian follicles in
reproductive age women
 Presents with menopause between
puberty and age 40
 Decreased estrogen
 Increased LH, FSH (decreased
feedback inhibition)

Polycystic Ovarian Syndrome,
465
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Increased LH/FSH ratio leads to
anovulation
Hyperandrogenism
Enlarged, bilateral cystic ovaries
Presents with amenorrhea, infertility,
obesity, hirsutism
Associated with insulin resistance,
increased risk of endometrial cancer
Treat with weight loss, OCP’s,
gonadotropin analogs, clomiphene, surgery
Ovarian Cysts, 465

Follicular cyst
 Distentension of unruptured graafian follicle
 Associated with hyperestrinism, endometrial
hyperplasia
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Corpus luteum cyst
 Hemorrhage into persistent
corpus luteum
 Associated with menstrual
irregularity
Ovarian Cysts, 465

Theca-lutein cyst
 Bilateral/multiple, due to gonadotropin
stimulation
 Associated with choriocarcinoma and moles
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“Chocolate cyst”
 Blood containing cyst from
ovarian endometriosis
 Varies with menstrual cycle
Ovarian Germ Cell Tumors, 465
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Dysgerminoma
 Malignant, equivalent to male seminoma
 Sheets of uniform cells
 hCG tumor marker
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Choriocarcinoma
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Rare, malignant
Can develop in pregnancy (mother or fetus)
Large hyperchromatic synctiotrophoblastic cells
Increased frequency of theca-lutein cysts
hCG tumor marker
Ovarian Germ Cell Tumors, 465
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Yolk sac (endodermal sinus) tumor
 Aggressive malignancy in ovaries,
sacrococcygeal area (children)
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Teratoma
 Contains 2-3 germ layers
 Mature teratoma (dermoid cyst)
○ Most common benign tumor
 Immature teratoma
○ Aggressively malignant
 Struma ovarii
○ Contains functional thyroid tissue
Ovarian Non-germ Cell Tumors,
466
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Brenner tumor
 Benign, looks like bladder
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Fibromas
 Bundles of spindle-shaped fibroblasts
 Meig’s syndrome
○ Ovarian fibroma, ascites, hydrothorax
 Pulling sensation in groin
Ovarian Non-germ Cell Tumors,
466
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Granulosa cell tumor
 Estrogen secreting
○ Precocious puberty
○ Endometrial hyperplasia or carcinoma
 Call-exner bodies
○ Small follicles with
eosinophilic secretions
Ovarian Non-germ Cell Tumors,
466
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Krukenberg tumor
 GI malignancy that metastasizes to ovary
 Mucin-secreting signet cell adenocarcinoma
Ovarian Non-germ Cell Tumors,
466
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Serous cystadenoma
 Benign, bilateral, lined with fallopian tube
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Serous cystadenocarcinoma
 Malignant, bilateral
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Mucinous cystadenocarcinoma
 Malignant
 Pseudomyxoma peritonei
○ Accumulation of mucinous material from
ovarian or appendiceal tumor
Vaginal Carcinoma, 466

Squamous cell carcinoma
 Secondary to cervical SCC

Clear cell adenocarcinoma
 Associated with in utero exposure to DES
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Sarcoma botyroides
 Girls <4 years
 Spindle shaped tumors
 Desmin positive
Benign Breast Tumors, 466

Fibroadenoma
 Small, mobile, firm mass with sharp edges
 Most common in <25 years
 Increase in size and tenderness with
estrogen
 Not pre-malignant
Benign Breast Tumors, 466
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Intraductal papilloma
 Small, grows in lactiferous ducts
 Typically beneath areola
 Serous/bloody discharge
 Slightly increases risk of carcinoma
Benign Breast Tumors, 466

Phyllodes Tumor
 Large, bulky mass of connective tissue and
cysts
 “Leaf-like” projections
 Most common in 6th decade
 May become malignant
Malignant Breast Tumors, 467
Common in post-menopause
 Arise from mammary duct epithelium or
lobular glands
 Overexpression of
estrogen/progesterone receptors erb-B2
affects therapy and prognosis
 Axillary lymph node involvement is most
important prognostic factor

Malignant Breast Tumors, 467
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Ductal carcinoma in situ
 Fills ductal lumen
 Early malignancy without basement
membrane penetration
Malignant Breast Tumors, 467
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Invasive ductal
 Firm, fibrous mass
 Small, glandular, duct-like cells
 Most invasive and common
Malignant Breast Tumors, 467
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Invasive lobular
 Orderly rows of cells
 Multiple, bilateral
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Medullary
 Fleshy, cellular,
lymphatic infiltrate
 Good prognosis
Malignant Breast Tumors, 467
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Comedocarcinoma
 Ductal, caseous necrosis

Inflammatory
 Dermal lymphatic invasion
by breast carcinoma
 Peau d’orange
 Poor survival rate
Common Breast Conditions, 468
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Fibrocystic disease
 Most common “breast lumps” from age 25-
menopause
 Premenstrual breast pain, multiple bilateral
lesions, fluctuating size
 Does not indicate increased risk of
carcinoma
Common Breast Conditions, 468

Fibrocystic disease
 Fibrosis
○ Hyperplasia of breast stroma
 Cystic
○ Fluid filled, blue dome
 Sclerosing adenosis
○ Increased acini and intralobular fibrosis
 Epithelial hyperplasia
○ Increased epithelial cell
layers in terminal duct lobule
○ Increased risk of carcinoma with
atypical cells
Common Breast Conditions, 468

Acute Mastitis
 Breast abscess
 Associated with breast feeding
○ Bacterial infection through cracks in nipples
 Most common pathogen is S. aureus
Common Breast Conditions, 468

Fat Necrosis
 Benign painless breast lump
 Secondary to injury to breast tissue
Common Breast Conditions, 468

Gynecomastia
 Results from hyperestrogenism
○ Cirrhosis, testicular tumor, puberty, old age
 Klinefelter’s syndrome
 Drugs
○ Estrogen, marijuana, heroin, psychoactive
drugs, spironolactone, digitalis, cimetidine,
alcohol, ketoconazole
Benign Prostatic Hyperplasia,
468
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Common in men >50
Related to age-related increase in
estradiol, sensitization of prostate to DHT
Nodular enlargement of periurethral (lateral
and middle) lobes, compresses urethra into
vertical slit
Presents with frequency, nocturia,
hesitancy, dysuria
May lead to distention/hypertrophy of
bladder, hydronephrosis, UTIs
Increased PSA, not premalignant
Prostatitis, 469

Symptoms
 Dysuria, frequency, urgency, low back pain

Etiology
 Acute: bacterial
 Chronic: abacterial (most common),
bacterial
Prostatic Adenocarcinoma, 469
More common in men >50 years
 Usually develops in posterior lobe
(peripheral zone) of prostate
 Diagnosed by DRE and biopsy

Prostatic Adenocarcinoma, 469

PSA tumor marker
 Increased PSA, decreased fraction of free
PSA

Osteoblastic metastasis
 Low back pain
 Increased serum
alkaline phosphatase
Cryptorchidism, 469
Undescended testis
 Decreased spermatogenesis secondary
to increased body temperature
 Increased risk of germ cell tumors
 Prematurity increases occurrence

Testicular Germ Cell Tumors, 469
95% of all testicular tumors
 Seminoma

 Malignant, most common testicular tumor
 Painless testicular enlargement
 Males 15-35
 Radiosensitive, late metastasis
 Excellent prognosis
Testicular Germ Cell Tumors, 469

Seminoma
 Large cells in lobules with watery cytoplasm,
“fried egg” appearance
Testicular Germ Cell Tumors, 469

Embryonal carcinoma
 Malignant
 Painful testicular enlargement
 Worse prognosis
 Glandular/papillary
morphology
 Can differentiate to
other tumors
Testicular Germ Cell Tumor, 469

Yolk sac (endodermal sinus) tumor
 Analogous to ovarian yolk sac tumor
 Schiller-Duval bodes
○ Central vessel surrounded
by tumor cells
 Primitive glomeruli
 Increased AFP
Testicular Germ Cell Tumors, 469

Choriocarcinoma
 Malignant
 Increased hCG

Teratoma
 Usually malignant
Testicular Non-germ Cell Tumors,
469
5% of testicular tumors, mostly benign
 Leydig cell tumor

 Intracytoplasmic Reinke crystals,
 Androgen producing
○ Gynecomastia
○ Precocious puberty
Testicular Non-germ cell Tumors,
469

Sertoli cell tumor
 Androblastoma from
sex cord stroma

Testicular lymphoma
 Most common testicular
cancer in older men
Tunica Vaginalis Lesions, 469
Lesions in serous covering of testes
 Present as testicular masses that
transilluminate


Varicocele
 Dilated vein in pampiniform
plexus “bag of worms”
 May cause infertility
Tunica Vaginalis Lesions, 469

Hydrocele
 Increased fluid secondary to incomplete
fusion of processus vaginalis

Spermatocele
 Dilated epididymal duct
Penile Pathology, 470

Carcinoma in situ
 Bowen’s disease
○ Gray, solitary, crusty plaque
○ Usually on shaft of penis or scrotum
○ Peak incidence in 5th decade
○ Progresses to sqamous cell carcinoma in
<10% of cases
Penile Pathology, 470

Carcinoma in situ
 Erythroplasia of Queyrat
○ Red, velvety plaques
○ Usually involves glans
○ Similar to Bowen’s disease
Penile Pathology, 470

Carcinoma in situ
 Bowenoid papulosis
○ Multiple papular lesions
○ Affects younger age group
○ Usually not invasive
Penile Pathology, 470

Squamous cell carcinoma
 More common in uncircumcised men
 More common in Asia, Africa, S. America
 Associated with HPV
Penile Pathology, 470

Peyronie’s disease
 Bent penis
 Aquired fibrous tissue formation
Anti-androgens, 471

Finasteride
 5 α reductase inhibitor
 Decreases conversion of testosterone to
more potent DHT
 Used in BPH, male pattern baldness

Flutamide
 Non-steroidal competitive inhibitor of
testosterone receptor
 Used in prostate carcinoma
Anti-androgens, 471

Ketoconazole
 Inhibits steroid synthesis

Spironolactone
 Inhibits steroid binding
Both used in treatment of PCOS and
hirsutism
 May cause gynecomastia, amenorrhea

Leuprolide, 471

Pulsatile administration
 GnRH analog with agonist properties

Continuous administration
 GnRH analog with antagonist properties

Used in
 Infertility (pulsatile), prostate cancer
(continuous with flutamide), uterine fibroids

May have anti-androgen effects, nausea
vomiting
Sildenafil, vardenafil, 471
Inhibit cGMP phosphodiesterase, causing
increased CGMP, smooth muscle
relaxation in corpus cavernosum,
increased blood flow, erection
 Used in treatment of impotency
 May cause headache, flushing, dyspepsia,
impaired blue/green colorvision
 Risk of life threatening hypotension if taken
with nitrates

Mifepristone (RU-486), 471
Competitive inhibitor of progesterone
receptors
 Used in termination of pregnancy

 Makes uterus inhospitable to fertilized egg
 Administered with misoprostole

May cause heavy bleeding,
nausea/vomiting, anorexia, abdominal
pain
Oral Contraception, 471

Prevent estrogen surge
 Estrogen surge, LH surge do not occur

Pros:
 Reliable
 Decrease risk of endometrial/ovarian cancer,
ectopic pregnancy, pelvic infections,
regulation of menses

Cons:
 Increased triglycerides, weight gain, nausea,
hypertension, hypercoaguable state
Hormone Replacement Therapy,
471

Used in:
 Treatment of menopausal symptoms
○ Hot flashes, vaginal atrophy
 Prevention of osteoporosis

Unopposed estrogen (without
progestins) increases risk of endometrial
cancer
 Give progestins if patient has not had
hysterectomy

Increase in CV risk (pro-thrombotic)
Induction/delay of Labor, 472

Dinoprostone
 PGE2 analog
 Causes cervical dilation, uterine contraction
 Induces labor

Ritodrine/terbutaline
 B2 agonists
 Relax uterus
 Reduce premature uterine contractions
 Delay labor
Anastrozole/exemestane, 472

Aromatase inhibitors
 Aromatase converts androgens to estrogens

Used in post-menopausal breast cancer
 Adjuvant therapy after surgery
 Metastatic disease
Testosterone, 472
Agonist at androgen receptors
 Used in:

 Treatment of hypogonadism
 Promotion of development of secondary
sexual characteristics
 Stimulation of anabolism (burn, injury)
 Treatment of ER-positive breast cancer
Testosterone Toxicity, 472
Masculinization in females
 Exogenous use reduces intratesticular
testosterone, inhibits Leydig cells, leads
to testicular atrophy
 Premature closure of epiphyseal plates
(short stature)
 Dyslipidemia

Estrogens, 472
Bind estrogen receptors
 Used in:

 Treatment of hypogonadism/ovarian failure
 Treatment of menstrual abnormalities
 Hormone replacement therapy in post-
menopause
 Treatment of men with androgen-dependent
prostate cancer
Estrogen Toxicity, 472
Increased risk of endometrial cancer
 Increased bleeding in post-menopause
 Increases risk of clear cell
adenocarcinoma with prenatal DES
 Increased risk of thrombi


Contraindicated in estrogen-receptor
positive breast cancer
Progestins, 472
Bind progesterone receptors
 Reduce growth and increase
vascularization of endometrium
 Used in:

 Oral contraceptives
 Treatment of endometrial cancer
 Treatment of abnormal uterine bleeding
Estrogen Partial Agonists, 472

Clomiphene
 Partial agonist at estrogen receptors in




pituitary
Prevents estrogen feedback inhibition of
LH/FSH release from pituitary
Increased LH/FHS stimulates ovulation
Used in treatment of PCOS and infertility
May cause hot flashes, ovarian
enlargement, multiple simultaneous
pregnancies, visual disturbances
Estrogen Partial Agonists, 472

Tamoxifen
 Estrogen antagonist in breast tissue
 Used to treat and prevent recurrence of ER-
positive breast cancer

Raloxifene
 Estrogen agonist in bone
 Used to treat osteoporosis