USMLE STEP I REVIEW: Week 4 Reproductive

1
USMLE STEP I REVIEWWeek 4Reproductive

• Chase Findley, MSIV

2
Gonadal Drainage, 454

• Venous
• Left ovary/testis, left gonadal vein, left renal
  vein, IVC
• Lymphatic
• Ovaries/testes,
• para-aortic
• lymph nodes

3
Derivation of Sperm Parts, 455

• Acrosome
• Golgi apparatus
• Neck
• Contains mitochondria
• Utilizes fructose
• Tail (flagellum)
• Centrioles

4
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

5
Male Reproductive Anatomy, 455
6
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

7
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

8
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

9
Androgens, 458

• DHT function
• Differentiate penis, scrotum, prostate
• Balding
• Increased sebaceous gland actitivity
• Prostate growth

10
Androgens, 458

• Potency
• DHTgttestosteronegtandrostenedione
• 5 a reductase
• Converts testosterone to DHT, inhibited by
  finasteride
• Aromatase
• Converts testosterone/androstenedione to estrogen
  in adipose tissue and Sertoli cells

11
Estrogens, 458

• 17ß 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

12
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

13
Menstrual Cycle, 459
14
Oogenesis, 460
15
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 ßHCG, detectable in urine 1
  week after conception

16
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

17
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

18
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

19
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

20
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

21
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

22
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

23
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

24
5a Reductase Deficiency, 462

• Unable to convert testosterone to DHT
• Ambiguous genitalia until puberty
• Increased testosterone causes masculinization of
  external genitalia
• Testosterone/estrogen levels normal

25
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

26
Placenta Accreta, 463

• Defective decidual layer
• Placenta attaches to myometrium
• Increased risk with prior c-section or uterine
  inflammation
• Massive bleeding after
• delivery

27
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

28
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

29
Amniotic Fluid Abnormalities, 463

• Polyhydramnios
• gt1.5-2 L amniotic fluid
• Associated with esophageal/duodenal atresia
  (inability to swallow amniotic fluid) and
  anencephaly
• Oligohydramnios
• lt0.5 L amniotic fluid
• Associated with bilateral renal agenesis and
  posterior urethral valves (inability to secrete
  urine)

30
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

31
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

32
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

33
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

34
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

35
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

36
Myometrial Tumors, 464

• Leiomyoma
• May be asymptomatic or cause abnormal uterine
  bleeding
• May cause iron deficient anemia
• Whorled pattern of smooth muscle bundles

37
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

38
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)

39
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

40
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

41
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

42
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

43
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

44
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

45
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

46
Ovarian Non-germ Cell Tumors, 466

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

47
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

48
Vaginal Carcinoma, 466

• Squamous cell carcinoma
• Secondary to cervical SCC
• Clear cell adenocarcinoma
• Associated with in utero exposure to DES
• Sarcoma botyroides
• Girls lt4 years
• Spindle shaped tumors
• Desmin positive

49
Benign Breast Tumors, 466

• Fibroadenoma
• Small, mobile, firm mass with sharp edges
• Most common in lt25 years
• Increase in size and tenderness with estrogen
• Not pre-malignant

50
Benign Breast Tumors, 466

• Intraductal papilloma
• Small, grows in lactiferous ducts
• Typically beneath areola
• Serous/bloody discharge
• Slightly increases risk of carcinoma

51
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

52
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

53
Malignant Breast Tumors, 467

• Ductal carcinoma in situ
• Fills ductal lumen
• Early malignancy without basement membrane
  penetration

54
Malignant Breast Tumors, 467

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

55
Malignant Breast Tumors, 467

• Invasive lobular
• Orderly rows of cells
• Multiple, bilateral
• Medullary
• Fleshy, cellular,
• lymphatic infiltrate
• Good prognosis

56
Malignant Breast Tumors, 467

• Comedocarcinoma
• Ductal, caseous necrosis
• Inflammatory
• Dermal lymphatic invasion
• by breast carcinoma
• Peau dorange
• Poor survival rate

57
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

58
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

59
Common Breast Conditions, 468

• Acute Mastitis
• Breast abscess
• Associated with breast feeding
• Bacterial infection through cracks in nipples
• Most common pathogen is S. aureus

60
Common Breast Conditions, 468

• Fat Necrosis
• Benign painless breast lump
• Secondary to injury to breast tissue

61
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

62
Benign Prostatic Hyperplasia, 468

• Common in men gt50
• 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

63
Prostatitis, 469

• Symptoms
• Dysuria, frequency, urgency, low back pain
• Etiology
• Acute bacterial
• Chronic abacterial (most common), bacterial

64
Prostatic Adenocarcinoma, 469

• More common in men gt50 years
• Usually develops in posterior lobe (peripheral
  zone) of prostate
• Diagnosed by DRE and biopsy

65
Prostatic Adenocarcinoma, 469

• PSA tumor marker
• Increased PSA, decreased fraction of free PSA
• Osteoblastic metastasis
• Low back pain
• Increased serum
• alkaline phosphatase

66
Cryptorchidism, 469

• Undescended testis
• Decreased spermatogenesis secondary to increased
  body temperature
• Increased risk of germ cell tumors
• Prematurity increases occurrence

67
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

68
Testicular Germ Cell Tumors, 469

• Seminoma
• Large cells in lobules with watery cytoplasm,
  fried egg appearance

69
Testicular Germ Cell Tumors, 469

• Embryonal carcinoma
• Malignant
• Painful testicular enlargement
• Worse prognosis
• Glandular/papillary
• morphology
• Can differentiate to
• other tumors

70
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

71
Testicular Germ Cell Tumors, 469

• Choriocarcinoma
• Malignant
• Increased hCG
• Teratoma
• Usually malignant

72
Testicular Non-germ Cell Tumors, 469

• 5 of testicular tumors, mostly benign
• Leydig cell tumor
• Intracytoplasmic Reinke crystals,
• Androgen producing
• Gynecomastia
• Precocious puberty

73
Testicular Non-germ cell Tumors, 469

• Sertoli cell tumor
• Androblastoma from
• sex cord stroma
• Testicular lymphoma
• Most common testicular
• cancer in older men

74
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

75
Tunica Vaginalis Lesions, 469

• Hydrocele
• Increased fluid secondary to incomplete fusion of
  processus vaginalis
• Spermatocele
• Dilated epididymal duct

76
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 lt10 of
  cases

77
Penile Pathology, 470

• Carcinoma in situ
• Erythroplasia of Queyrat
• Red, velvety plaques
• Usually involves glans
• Similar to Bowens disease

78
Penile Pathology, 470

• Carcinoma in situ
• Bowenoid papulosis
• Multiple papular lesions
• Affects younger age group
• Usually not invasive

79
Penile Pathology, 470

• Squamous cell carcinoma
• More common in uncircumcised men
• More common in Asia, Africa, S. America
• Associated with HPV

80
Penile Pathology, 470

• Peyronies disease
• Bent penis
• Aquired fibrous tissue formation

81
Anti-androgens, 471

• Finasteride
• 5 a 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

82
Anti-androgens, 471

• Ketoconazole
• Inhibits steroid synthesis
• Spironolactone
• Inhibits steroid binding
• Both used in treatment of PCOS and hirsutism
• May cause gynecomastia, amenorrhea

83
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

84
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

85
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

86
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

87
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)

88
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

89
Anastrozole/exemestane, 472

• Aromatase inhibitors
• Aromatase converts androgens to estrogens
• Used in post-menopausal breast cancer
• Adjuvant therapy after surgery
• Metastatic disease

90
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

91
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

92
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

93
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

94
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

95
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

96
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