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