lect 1-pathophys repro

Pathophysiology of Reproductive System

SMS3033

Dr. Mohanad R. Alwan

Reproductive System DisordersReproductive System Disorders

Pathophysiology

Overview

A. Ovaries

B. Oviducts

C. Uterus

D. (vagina & external genitalia)

E. (mammary glands)

• Anatomy gonads = ovaries ductal system accessory glands external genitalia

Female Reproductive Female Reproductive SystemSystem

I. Ovaries

A. medulla

1. CT

2. vascular

B. cortex

1. follicles

2. germinal epithelium

3. tunica albuginea

• Ovaries– contain gametes (oocytes) surrounded by

some cells (follicular cells)

– these called Primary Follicles

» each ovary has appox. 1 million at birth

– life cycle of oocyte after puberty: primary

oocyte, secondary oocyte, ovum– FUNCTIONS

• Gamete production

• Hormone production

– Estrogen = causes feminization ; from granulosa cells

– Progesterone = prepares for pregnancy ; from corpus luteum

II. OogenesisA. Oogonia 1. migrate to ovary from yolk

sac 2. mitosis until 5 mo.B. Primary oocytes 1. prophase of 1st meiotic div. 2. 3rd-7th mo.C. Secondary oocyte 1. just before ovulation 2. first meiotic div. 3. first polar body + oocyte 4. ovum viable for 24 hrs.

OogenesisD. Second meiotic division

1. complete only after fertilization

2. second polar body + ♀ pronucleus

3. zygote = ♂ + ♀ pronuclei fuse

4. mitotic div.

II I. Follicle Development

A. Primordial follicle

1. primary oocyte

a. ~25 m diameter

2. single layer of flat follicular (granulosa) cells

a. desmosomes

Follicle DevelopmentB. Primary follicle

1. primary oocyte

a. growth to 125-150 m diam.

2. follicular cells

a. cuboidal cells

b. 1 to many layers

c. gap junctions

Follicle Development

B. Primary follicle

Follicle Development

B. Primary follicle

3. zona pellucida

Follicle Development

B. Primary follicle

4. theca folliculi

a. theca interna

1) source of estrodiol precursor

b. theca externa

1) CT

Follicle Development

C. Secondary (vesicular) follicle

1. antrum a. liquor folliculi 2. cumulus oophorus 3. oocyte at maximal

diameter 4. 1st meiotic division:

secondary oocyte & 1st polar body (not visible)

Follicle DevelopmentD. Mature (graafian) follicle

1. ~2.5 cm diameter 2. located near ovary surface

3. corona radiata 4. secondary oocyte

Follicle Development

E. Follicular atresia

1. degeneration of follicle

2. phagocytosis of follicle

3. may occur at any stage of follicular development

Follicle Development

E. Follicular atresia

4. interstitial cells

a. persistent theca interna cells

b. secrete androgens

Follicle Development

F. Ovulation

1. ~ day 14 of menstrual

cycle

2. release of ovum with

corona radiata

3. received by fimbriae of oviduct

4. fertilization usually in oviduct (triggers 2nd meiotic division with second polar body)

5. male & female pronuclei fuse = zygote

Follicle Development

G. Corpus Luteum

1. remains after ovulation

2. granulosa & theca interna cells

a. steroid secreting

b. granulosa lutein cells

c. theca lutein cells

3. progesterone & estrogens

Follicle DevelopmentCorpus luteum – granulosa lutein cells

Follicle DevelopmentG. Corpus luteum of menstruation

1. no fertilization

2. after 10-14 days corpus luteum degenerates

Follicle DevelopmentH. corpus luteum of

pregnancy

1. maintained by human

chorionic gonadotropin

(HCG)

a. from placenta

2. secretes steroids during pregnancy

3. secretes relaxin

a. softens pubic symphysis

Follicle Development

I. Corpus albicans

1. replaces corpus luteum

2. CT scar tissue

• Female Ductal System– Fallopian Tubes

• distal end = fimbria

• Outer 1/3 = fertilization

– Uterus

• composed of fundus, body, & cervix

• has myometrium & endometrium]

– Vagina

• Accessory Glands– Bartholin’s (greater vestibular)

• exocrine gland

• provides lubrication

– Breasts

• composed of glands & ducts surrounded by fat tissue

• External Genitalia– clitoris, labia majora & minora (no hair follicles), vestibule, perineum

II.OviductsA. Between uterus and ovaries

1. ~ 12 cm long 2. fimbriae

VI. OviductsB. Mucosa

1. longitudinal folds

Oviducts

B. Mucosa

2. simple columnar epithelium

a. ciliated cells

b. secretory cells

1) supports / transports ovum

2) capacitation

Oviducts

C. Muscularis

1. inner circular layer

2. outer longitudinal layer

OviductsD. Serosa

1. visceral peritoneum

V. UterusA. Gross anatomy

1. fundus

2. body

3. cervix

Uterus

B. Layers

1. serosa / adventitia

2. myometrium

3. endometrium

Uterus

C. Myometrium

1. poorly organized layers

2. smooth muscle fibers

UterusD. Endometrium

1. simple columnar epithelium

a. ciliated cells

b. secretory cells

2. lamina propria

a. loose CT

b. uterine glands

UterusD. Endometrium

3. functionalis

a. coiled arteries

4. basalis

a. straight arteries

The Menstrual Cycle

– begins after menarche ; ends with menopause

– 4 basic parts:– Menses– Proliferative Phase = first

half of cycle-deals with maturation of follicle & development of more granulosa cells thus producing more estrogen

– Ovulation = usually at midcycle

– Secretory Phase = second half of cycle

– deals with conversion of ruptured follicle to corpus luteum

– corpus luteum produces progesterone

VI. Menstrual CycleA. Menstrual phase 1. days 1-4 2. begins with

menstrual flow 3. no fertilization

4. corpus luteum degenerates a. drop in progesterone and estrogens 5. coiled arteries constrict 6. ischemia & necrosis of functionalis 7. shedding of functionalis.

VII. Menstrual Cycle

B. Proliferative phase

1. days 5-14

2. coincides with development of ovarian follicles

3. regeneration

a. surface epithelium

b. lamina propria

c. uterine glands

d. coiled arteries

VII. Menstrual CycleC. Secretory phase

1. days 15-28

2. begins after ovulation

3. depends on corpus luteum secretions

4. uterine glands become coiled and distended

5. prepared to receive zygote

• Hormonal Control• hypothalamus--------GnRH (gonadotropin releasing hormone)

• anterior pituitary---- FSH (follicle stimulating hormone)

LH (luteinizing hormone)

• Ovary --------------- Estrogen

Progesterone

Female reproductive tract disordersOverall Outline

• Structural abnormalities

• Menstrual disorders

– Endometriosis

– Menopause

• Infections

• Tumors– Benign

– Malignant

• Breast

• Pregnancy

• STD’s

Structural abnormalities

• Pelvic relaxation disorders– Normal variations of uterine position

• Uterine mobility is key to normalcy – Uterine prolapse

– First, second, & third degrees– Cystocele– Rectocele

Normal variations of uterine position

– Uterine mobility is key to normalcy

– midline

– Anteverted & anteflexed

– Retroverted & retroflexed

"retroverted": tipped backwards "retroflexed": the fundus is pointing backwards. Anterior of uterus is convex.

Uterine Prolapse• def = downward

displacement of uterus

• etiol = fascial tissue defect

• First degree

• Get vaginal shortening

• Second degree

• Cervix at introitus

• Third degree

• Vagina completely everted

• Uterus hanging outside vagina

• Cystocele• downward displacement of bladder

into vagina• Can get retention & frequent

cystitis• urethra may or may not accompany

it» called cysto-urethrocele» frequently get symptom of

urinary stress incontinence

• Rectocele• displacement of rectum into vagina

• Usually asymptomatic

• If very large may get constipation & inability to completely evacuate rectum

• May get ulceration of vaginal wall• See picture

• Dysmenorrhea– Primary dysmenorrhea = when no obvious pathology found

– ? Hormonal cause » prostaglandins» hormonal changes secondary to teenage ovulatory cycles

– Secondary dysmenorrhea = when obvious pathology found as the cause

• Amenorrhea– Primary Amenorrhea = never having a menstrual flow– Secondary Amenorrhea = having menstrual cycles & then they stop– causes = many !!!

» Treatment directed at the underlying cause

Menstrual DisordersMenstrual Disorders

• Dysfunctional Uterine Bleeding (DUB)– abnormal menstrual flow when no obvious cause is known

– frequently thought to be secondary to some type of hormonal imbalance, but specific diagnosis not necessary to have DUB

– Types:» oligomenorrhea » polymenorrhea» menorrhagia» metrorrhagia» meno-metrorrhagia

• Premenstrual Syndrome (PMS)– group of symptoms that occur in the woman’s secretory phase of cycle– Currently called : PMDD (premenstrual dysphoric disorder)

• Def of dysphoria = excessive pain, anguish, & agitation

– usually secondary to inappropriate ovulation– Key = too much estrogen & not enough progesterone in the second half of the cycle

• Endometriosis– A condition when you get

endometrial tissue located outside its normal position, which is the inside lining of the uterus

– symptoms depend on where the ectopic tissue is located

– the tissue has function, i.e.

bleeds with menstruation

– Sx : pain

– Complications

• Fibrosis

• Scarring

• Adhesions

• Infertility

• Dyspareunia

• menopause– Get cessation of menses & drop in estrogens which can cause:

– general symptoms

» irritability

» short term memory loss

» Insomnia

» Vasomotor instability = hot flashes & night sweats

– gynecological symptoms

» vaginal dryness & dyspareunia

» urinary stress incontinence

– Cardiovascular problems

» ASHD

» coronary artery disease

» strokes

– Osteoporosis

– Dx:

– High FSH; low estrogens

• Vaginitis– 3 types:

• Yeast Vaginitis– caused by fungus from genus Candida or Monilia

• Trichomonas

– caused by a protozoa

– may be sexually transmitted

• Bacterial Vaginosis

– caused by different bacterial overgrowth

– used to be called non-specific vaginitis or Gardnella

• Generally most cases of vaginitis are NOT sexually transmitted, but at times they ALL may be sexually transmitted !!

Infections of the Female Reproductive TractInfections of the Female Reproductive Tract

• Pelvic Inflammatory Disease (PID)– usually acute, but may be chronic

– may involve some or all of the pelvic organs

– get tissue inflammatory reaction with resultant symptoms

– Key symptom = pelvic pain

– Pain worsens with movement & sex

– frequently secondary to untreated or inadequately treated STD

– Complications

– Infertility (pyosalpinx)

– Adhesions

– Dysuria

– Irregular vaginal bleeding

See next slide

• Note PID spread:– Vaginitis

– Cervicitis

– Endometritis

– Oophoritis

• Toxic Shock Syndrome (TSS)– vaginal infection with systemic symptoms

– caused by staphlococci toxin which comes from nidus of infected tampon

– prevention by proper tampon toilet

– Symptoms begin immediately post menses

Bartholin cyst (Bartholinitis) Etiol = pathogens that cause inflammation Duct become obstructed

Get “large pimple”

TumorsTumors of the Female Reproductive Tract of the Female Reproductive Tract

• Cervix– Benign

• Cervical polyps

– malignant• key ages: 20 - 40• pap smear• Etiol: HPV

– Vaccine available

• Uterus– benign

• fibroids = commonest tumor of female repo. System

– leiomyomas– only in premenopause– See next slide

– malignant• ? Estrogen related• Age: 50 – 70• Dx: pmb

• Estimated that half the women get them during the reproductive years

• Clinically symptoms depend on size & location

• Submucous = bleeding problems, infertility

• Intramural = sx only if large

• Subserous = pressure sx from surrounding structures

• Ovary– Benign

• Functional (commonest)– Follicular cyst– Corpus luteum cyst

• Non-functional (benign germ cell)

(e.g. Teratoma)

– Malignant• Factors that suppress ovulation

decrease the risk• Avg age = 40• 2 basic types

– Epithelial (line ovary or

follicles)– Germ cell – aggressive

» Mainly in children & adolescents

• See next slide re:– Late diagnoses – seeding

Solid teratoma

Functional (follicular) cyst

Breast disorders• Fibrocystic breasts

• Was called fibrocystic “disease”

• “lumpy” breasts

• Fibroadenoma• Benign

• In young girls (age 15-25)

• nontender

• Intraductile papilloma• Get nipple discharge

• Mammary duct ectasia– Get lumpiness beneath areola

– Seen in

– Postmenopausal

– Pregnancy

– Lactation

– Get thick nipple discharge

– Pathophysiology: ducts dilate & fill with cellular debris; get inflammation

• Breast cancer– 1 out of 8 women in USA

– Most are intraductile carcinomas

– 50% in upper outer quadrant

– Ca in situ = mammary dysplasia

– Risk factors:

– Family history

– Menstrual history

– Reproductive history

• Morning Sickness– severe form = Hyperemesis Gravidarum

• Spontaneous Abortion– 3 Types : Complete, Incomplete, Missed

• Ectopic Pregnancy• Toxemia of Pregnancy = syndrome of hypertension, proteinuria,

& edema• called Preeclampsia• If severe & accompanied by convulsions, called Eclampsia

• Placental Problems– Placenta Praevia– Abruptio Placenta

• Hydatidiform Mole = development abnormality of conception• may progress to Choriocarcinoma

Pathology in PregnancyPathology in Pregnancy

• Preterm Birth – 8% of all births in US

– Preterm labor

– Preterm PROM (premature rupture of membranes)

» Responsible for half of all premie deliveries in US

• Trauma during pregnancy– Complicates 1 out of 12 pregnancies in US

– Watch for:» Uterine contractions» Uterine tenderness &/or irritability» Ruptured BOW» Nonreassuring FHR pattern» Vaginal bleeding

• Maternal hemorrhage– Is the leading cause of maternal mortality

– Hemorrhagic shock

– Postpartum hemorrhage

• Endometritis– Occurs in 1-3% of vaginal births

– Occurs in 10-50% of cesarean sections

STD’sSTD’s• AIDS (Acquired Immunodeficiency Syndrome)

• Def: progressive impairment of the immune system caused by the immunodeficiency virus (HIV)

– Attacks helper T lymphocytes

• Initial infection similar to URI• Then latency• Then AIDS

– Begins with generalized adenopathy, weight loss, fatigue, nt. Sweats, and diarrhea

– Get opportunistic infections:» PCP (pneumocystis carinii pneumonia) = caused by small

protozoa (? fungus) that can normally be found in lung tissue of certain animals (dogs) and in humans

» Toxoplasmosis = small protozoan that can infect many mammals including cats and dogs

» Herpes simplex» Herpes zoster (shingles)» TB

• AIDS (continued)– Get opportunistic cancers

» Non-Hodgkins lymphoma

» Kaposi’s sarcoma

• HIV also has predilection to attack G-I cells & CNS cells– Get malabsorption, colitis, and proctitis

– Dementia

• Diagnosis– ELISA (enzyme-linked immunosorbent assay)

– Western blot test

• Treatment– AZT = reverse transcriptase inhibitors

– Protease inhibitors

– Fusion inhibitors

• Chlamydia– Most frequent bacterial STD– Known as the “silent STD”– Transmitted via oral, anal, or genital intercourse

» Oral route can lead to conjunctivitis– If symptomatic, get urethritis – Incubation = 1-3 weeks

• Gonorrhea– Bacterial– Incubation = 1-3 weeks (usually less than 1 week)– Very similar in signs & symptoms to chlamydia– Antibiotic resistance

• Syphilis– Bacterial – Can get primary, secondary, and tertiary forms– New cases at an all time low– Primary = hard, painless chancre in 2-3 weeks ------------ see pictures– Secondary syphilis may appear 1-3 months later– Then latency for years & then possible tertiary syphilis

• Chancroid– Soft chancre (painful) with

bubo(necrotizing ulceration & lymphadenopathy) in 1 week

• See pictures

– Bacterial

– Frequent in developing tropical countries

– Increasing in urban USA

• Genital Herpes– Type I & type II

– Short incubation of 2-7 days

– See pictures

• Hepatitis B & C– Transmitted in body fluids

• Genital warts– Very contagious

– First exposure incidence:– 40% ---to--- 90%

– Viral; HPV– 120 different serotypes– A few cause dysplasia &

neoplasia– Condylomata accuminatum

– Benign growths– See picture

– Prolonged incubation of 1-6 months

– Most frequent STD– Estimated that 60% of

sexually active young women in USA have it

– New vaccine available