week4part2

7/27/2019 week4part2

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Chase Findley, MSIV


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Gonadal Drainage, 454

Venous

Left ovary/testis, left gonadal vein, left renal

vein, IVC

LymphaticOvaries/testes,

para-aortic

lymph nodes


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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


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Male Reproductive Anatomy,

455


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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


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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


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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


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Androgens, 458

DHT function

Differentiate penis, scrotum, prostate

Balding

Increased sebaceous gland actitivity

Prostate growth


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Androgens, 458

Potency

DHT>testosterone>androstenedione

5 reductase

Converts testosterone to DHT, inhibited by

finasteride

Aromatase

Converts testosterone/androstenedione toestrogen in adipose tissue and Sertoli cells


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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


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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, inhibitssperm entry to uterus

Increase body temperature

Inhibit FSH/LH

Uterine smooth muscle relaxation, preventcontractions


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Menstrual Cycle, 459


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Oogenesis, 460


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Pregnancy, 460

Fertilization most commonly occurs in

upper fallopian tube, within 1 day of

ovulation

Implantation in wall of uterus 6 daysafter fertlization

Trophoblasts secrete HCG, detectable

in urine 1 week after conception


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Pregnancy, 460

Lactation

After labor, decrease in steroids induces

lactation

Suckling maintains milk production byincreasing oxytocin and prolactin

Prolactin

Induces, maintains lactation, inhibits ovulation

Oxytocin Involved in milk letdown and uterine

contractions


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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


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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


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Klinefelters Syndrome, 461

XXY (male) Presence ofinactivated X chromosome (Barr

body)

Testicular atrophy, eunuchoid body shape,

tall, long extremities, female hairdistribution

Common cause ofhypogonadism

Dysgenesis of seminiferous tubules

Decreased inhibin, increased FSH Abnormal Leydig cell function

Decreased testosterone, increased LH,increased estrogen


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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


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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 presentAmbiguous genitalia


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Pseudohermaphroditism, 462

Disagreement between phenotypic and

gonadal sex

Female (XX)

Ovaries present

External genitalia virilized or ambiguous

Excessive ofexposure to androgenic

steroids during gestation Caused by congenital adrenal hyperplasia or

exogenous administration of androgens


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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


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5 Reductase Deficiency,

462 Unable to convert testosterone to DHT

Ambiguous genitalia until puberty

Increased testosterone causes

masculinization of external genitalia

Testosterone/estrogen levels normal


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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


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Placenta Accreta, 463

Defective decidual layer

Placenta attaches to myometrium

Increased risk with prior c-section or

uterine inflammation

Massive bleeding after

delivery


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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

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


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Amniotic Fluid Abnormalities,

463

Polyhydramnios

>1.5-2 L amniotic fluid

Associated with esophageal/duodenal

atresia (inability to swallow amniotic fluid)and anencephaly

Oligohydramnios


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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


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Cervical Pathology

Invasive carcinoma

Often squamous cell carcinoma

Pap smearused for early detection of

dysplasia (koilocytes) Lateral invasion can

block ureters, lead to

renal failure


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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


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Endometrial Proliferation, 464

Endometrial hyperplasia

Endometrial gland proliferation caused by

increased estrogen stimulation

Increased risk ofendometrial carcinoma Presents as post-menopausal bleeding

Risk factors include anovulatory cycles,

HRT, PCOS, granulosa cell tumor


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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 estrogentherapy, obesity, diabetes, HTN, nulliparity,

late menopause Deeper myometrial invasion worsens

prognonsis


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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


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Leiomyoma

May be asymptomatic or cause abnormal

uterine bleeding

May cause iron deficient anemia Whorled pattern of smooth muscle bundles


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Leiomyosarcoma

Bulky, irregular shaped tumor

Areas ofnecrosis, hemorrhage

Highly aggressive, likely to recur

Increased incidence in blacks

May protrude from cervix


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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)


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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


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Ovarian Cysts, 465

Follicular cyst

Distentension of unruptured graafian follicle

Associated with hyperestrinism, endometrial

hyperplasia Corpus luteum cyst

Hemorrhage into persistent

corpus luteumAssociated with menstrual

irregularity


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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


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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 oftheca-lutein cysts

hCG tumor marker


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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

O i N C ll T


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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

O i N C ll T


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466

Granulosa cell tumor

Estrogen secreting

Precocious puberty

Endometrial hyperplasia or carcinoma Call-exner bodies

Small follicles with

eosinophilic secretions

O i N C ll T


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466

Krukenberg tumor

GI malignancy that metastasizes to ovary

Mucin-secreting signet cell adenocarcinoma

O i N C ll T


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466

Serous cystadenoma

Benign, bilateral, lined with fallopian tube

Serous cystadenocarcinoma

Malignant, bilateral

Mucinous cystadenocarcinoma

Malignant

Pseudomyxoma peritoneiAccumulation of mucinous material from

ovarian or appendiceal tumor


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Vaginal Carcinoma, 466

Squamous cell carcinoma

Secondary to cervical SCC

Clear cell adenocarcinoma

Associated with in utero exposure to DES

Sarcoma botyroides

Girls


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Benign Breast Tumors, 466

Fibroadenoma

Small, mobile, firm mass with sharp edges

Most common in


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Intraductal papilloma

Small, grows in lactiferous ducts

Typically beneath areola

Serous/bloody discharge Slightly increases risk of carcinoma


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Phyllodes Tumor

Large, bulky mass of connective tissue and

cysts

Leaf-like projections Most common in 6th decade

May become malignant


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Malignant Breast Tumors, 467

Common in post-menopause

Arise from mammary duct epithelium or

lobular glands

Overexpression ofestrogen/progesterone receptors erb-B2

affects therapy and prognosis

Axillary lymph node involvement is mostimportant prognostic factor


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Ductal carcinoma in situ

Fills ductal lumen

Early malignancy without basement

membrane penetration


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Invasive ductal

Firm, fibrous mass

Small, glandular, duct-like cells

Most invasive and common


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Invasive lobular Orderly rows of cells

Multiple, bilateral

Medullary Fleshy, cellular,

lymphatic infiltrate

Good prognosis


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Comedocarcinoma

Ductal, caseous necrosis

Inflammatory

Dermal lymphatic invasion

by breast carcinoma

Peau dorange Poor survival rate

Common Breast Conditions


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Common Breast Conditions,

468

Fibrocystic disease

Most common breast lumps from age 25-

menopause

Premenstrual breast pain, multiple bilaterallesions, fluctuating size

Does not indicate increased risk of

carcinoma



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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



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468

Acute Mastitis

Breast abscess

Associated with breast feeding

Bacterial infection through cracks in nipples Most common pathogen is S. aureus



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468

Fat Necrosis

Benign painless breast lump

Secondary to injury to breast tissue



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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


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Benign Prostatic Hyperplasia,

468 Common in men >50 Related to age-related increase in

estradiol, sensitization of prostate to DHT

Nodular enlargement ofperiurethral (lateral

and middle) lobes, compresses urethra intovertical slit

Presents with frequency, nocturia,hesitancy, dysuria

May lead to distention/hypertrophy ofbladder, hydronephrosis, UTIs

Increased PSA, not premalignant


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Prostatitis, 469

Symptoms

Dysuria, frequency, urgency, low back pain

Etiology

Acute: bacterial

Chronic: abacterial (most common),

bacterial


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Prostatic Adenocarcinoma, 469

More common in men >50 years

Usually develops in posterior lobe

(peripheral zone) of prostate

Diagnosed by DRE and biopsy


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Prostatic Adenocarcinoma, 469

PSA tumor marker

Increased PSA, decreased fraction of free

PSA

Osteoblastic metastasis Low back pain

Increased serum

alkaline phosphatase


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Cryptorchidism, 469

Undescended testis

Decreased spermatogenesis secondary

to increased body temperature

Increased risk ofgerm cell tumors

Prematurity increases occurrence


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Testicular Germ Cell Tumors


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Testicular Germ Cell Tumors,

469

Seminoma

Large cells in lobules with watery cytoplasm,

fried egg appearance



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469

Embryonal carcinoma

Malignant

Painful testicular enlargement

Worse prognosis Glandular/papillary

morphology

Can differentiate to

other tumors

Testicular Germ Cell Tumor


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Testicular Germ Cell Tumor,

469

Yolk sac (endodermal sinus) tumor

Analogous to ovarian yolk sac tumor

Schiller-Duval bodes

Central vessel surroundedby tumor cells

Primitive glomeruli

Increased AFP



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469

Choriocarcinoma

Malignant

Increased hCG

Teratoma Usually malignant

Testicular Non-germ Cell


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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


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Testicular Non-germ cell

Tumors, 469

Sertoli cell tumor

Androblastoma from

sex cord stroma

Testicular lymphoma

Most common testicularcancer in older men

Tunica Vaginalis Lesions


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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


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Tunica Vaginalis Lesions,

469 Hydrocele

Increased fluid secondary to incomplete

fusion of processus vaginalis

Spermatocele Dilated epididymal duct


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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


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Carcinoma in situ

Erythroplasia of Queyrat

Red, velvety plaques

Usually involves glans Similar to Bowens disease

P il P h l 470


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Carcinoma in situ

Bowenoid papulosis

Multiple papular lesions

Affects younger age group Usually not invasive


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P il P th l 470


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Peyronies disease

Bent penis

Aquired fibrous tissue formation

A ti d 471


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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

A ti d 471


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Anti-androgens, 471

Ketoconazole

Inhibits steroid synthesis

Spironolactone

Inhibits steroid binding

Both used in treatment ofPCOS and

hirsutism May cause gynecomastia, amenorrhea


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Sild fil d fil 471


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Sildenafil, vardenafil, 471

Inhibit cGMP phosphodiesterase, causingincreased 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

Mif i t (RU 486) 471


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Mifepristone (RU-486), 471

Competitive inhibitor of progesteronereceptors

Used in termination of pregnancy

Makes uterus inhospitable to fertilized eggAdministered with misoprostole

May cause heavy bleeding,

nausea/vomiting, anorexia, abdominalpain

O l C t ti 471


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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


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o o e ep ace e t

Therapy, 471

Used in: Treatment ofmenopausal symptoms

Hot flashes, vaginal atrophy

Prevention ofosteoporosis

Unopposed estrogen (withoutprogestins) increases risk of endometrialcancer

Give progestins if patient has not hadhysterectomy

Increase in CV risk (pro-thrombotic)

Induction/delay of Labor,


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y ,

472 Dinoprostone

PGE2analog

Causes cervical dilation, uterine contraction

Induces labor Ritodrine/terbutaline

B2 agonists

Relax uterus Reduce premature uterine contractions

Delay labor

A t l / t 472


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Anastrozole/exemestane, 472

Aromatase inhibitorsAromatase converts androgens to estrogens

Used in post-menopausal breast cancer

Adjuvant therapy after surgery Metastatic disease


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Testosterone Toxicity 472


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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


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Estrogens, 472

Bind estrogen receptors

Used in:

Treatment ofhypogonadism/ovarian failure

Treatment ofmenstrual abnormalities Hormone replacement therapy in post-

menopause

Treatment of men with androgen-dependent

prostate cancer

Estrogen Toxicity 472


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Estrogen Toxicity, 472

Increased risk ofendometrial cancer

Increased bleeding in post-menopause

Increases risk of clear cell

adenocarcinoma with prenatal DES Increased risk of thrombi

Contraindicated in estrogen-receptorpositive breast cancer

Progestins 472


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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


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Estrogen Partial Agonists, 472

Clomiphene Partial agonist at estrogen receptors in

pituitary

Prevents estrogen feedback inhibition ofLH/FSH release from pituitary

Increased LH/FHS stimulates ovulation

Used in treatment of PCOS and infertility

May cause hot flashes, ovarianenlargement, multiple simultaneous

pregnancies, visual disturbances

Estrogen Partial Agonists 472


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Estrogen Partial Agonists, 472

Tamoxifen Estrogen antagonist in breast tissue

Used to treat and prevent recurrence ofER-

positive breast cancer Raloxifene

Estrogen agonist in bone

Used to treat osteoporosis

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