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 reductase
Converts testosterone to DHT, inhibited by

finasteride

Aromatase
Converts testosterone/androstenedione to

estrogen in adipose tissue and Sertoli cells

Estrogens, 458

17 estradiol (ovary) Estriol (placenta) Functions:

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

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 HCG, 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

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

Klinefelters 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

Decreased inhibin, increased FSH

Abnormal Leydig cell function

Decreased testosterone, increased LH,

increased estrogen

Turners 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

Double Y males
XYY (male)
Phenotypically normal, normal fertility Tall, acne, antisocial behavior

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

Reductase Deficiency, 462

Unable to convert testosterone to DHT Ambiguous genitalia until puberty
Increased testosterone causes

masculinization of external genitalia

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

Ectopic Pregnancy, 463

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

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

Endometrial carcinoma

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

Leiomyoma
Most common female tumor
Benign, smooth muscle tumor, with rare

malignant transformation Multiple tumors with well demarcated borders Most common in 20-40s, 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

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, OCPs, gonadotropin analogs, clomiphene, surgery

Ovarian Cysts, 465

Follicular cyst
Distentension of unruptured graafian follicle
Associated with hyperestrinism, endometrial

hyperplasia

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

Chocolate cyst
Blood containing cyst from

ovarian endometriosis Varies with menstrual cycle

Ovarian Germ Cell Tumors, 465

Dysgerminoma
Malignant, equivalent to male seminoma Sheets of uniform cells hCG tumor marker

Choriocarcinoma

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

Yolk sac (endodermal sinus) tumor

Aggressive malignancy in ovaries,

sacrococcygeal area (children)

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

Brenner tumor
Benign, looks like bladder

Fibromas
Bundles of spindle-shaped fibroblasts Meigs syndrome Ovarian fibroma, ascites, hydrothorax Pulling sensation in groin

Ovarian Non-germ Cell Tumors, 466

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

Krukenberg tumor
GI malignancy that metastasizes to ovary
Mucin-secreting signet cell adenocarcinoma

Ovarian Non-germ Cell Tumors, 466

Serous cystadenoma
Benign, bilateral, lined with fallopian tube

Serous cystadenocarcinoma
Malignant, bilateral

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

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

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

Ductal carcinoma in situ

Fills ductal lumen
Early malignancy without basement

membrane penetration

Malignant Breast Tumors, 467

Invasive ductal
Firm, fibrous mass
Small, glandular, duct-like cells Most invasive and common

Malignant Breast Tumors, 467

Invasive lobular
Orderly rows of cells Multiple, bilateral

Medullary
Fleshy, cellular,

lymphatic infiltrate Good prognosis

Malignant Breast Tumors, 467

Comedocarcinoma
Ductal, caseous necrosis

Inflammatory
Dermal lymphatic invasion

by breast carcinoma Peau dorange Poor survival rate

Common Breast Conditions, 468

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
Klinefelters syndrome

Drugs Estrogen, marijuana, heroin, psychoactive drugs, spironolactone, digitalis, cimetidine, alcohol, ketoconazole

Benign Prostatic Hyperplasia, 468

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
Bowens 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 Bowens 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

Peyronies disease
Bent penis
Aquired fibrous tissue formation

Anti-androgens, 471

Finasteride
5 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