Menstrual Cycle Lect 2013

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    Menstrual cycle

    Physiology

    Dr. Atef Abood

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    Ovaries

    Primordial follicle one layer of squamouslike follicle

    cells surrounds the oocyte

    Primary follicle two or more layers of cuboidalgranulosa cells enclose the oocyte

    Secondary follicle has a fluid-filled space betweengranulosa cells that coalesces to form a centralantrum

    Graafian follicle secondary follicle at its mostmature stage that bulges from the surface of theovary

    Ovulation ejection of the oocyte from the ripeningfollicle

    Corpus luteum ruptured follicle after ovulation

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    Oogenesis

    At puberty, one activated primary oocyte producestwo haploid cells

    The first polar body

    The secondary oocyte

    The secondary oocyte arrests in metaphase II and isovulated

    If penetrated by sperm the second oocyte completes

    meiosis II, yielding: One large ovum (the functional gamete)

    A tiny second polar body

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    Ovarian Cycle

    Monthly series of events associated with the

    maturation of an egg

    Follicular phase period of follicle growth

    (days 114)

    Luteal phase period of corpus luteum

    activity (days 1428)

    Ovulation occurs midcycle

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    Follicular Phase

    This phase is under the effect of FSH and to a little extent LH.

    It starts by activation of several; primordial follicles.

    At the 6th day only one follicle starts to grow rapidlybecoming a dominant follicle called the Graffian follicle while

    the others regress. The primordial follicle, directed by the oocyte, becomes a

    primary follicle

    Primary follicle becomes a secondary follicle The theca folliculi and granulosa cells cooperate to produce estrogens

    The zona pellucida forms around the oocyte The antrum is formed

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    Follicular Phase (Cont.)

    The secondary follicle becomes a vesicular

    follicle

    The antrum expands and isolates the oocyte and

    the corona radiata

    The full size follicle (vesicular follicle) bulges from

    the external surface of the ovary

    The primary oocyte completes meiosis I, and thestage is set for ovulation

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    Ovulation

    Ovulation occurs when the ovary wall ruptures

    and expels the secondary oocyte

    Mittelschmerz a twinge of pain sometimes

    felt at ovulation

    1-2% of ovulations release more than one

    secondary oocyte, which if fertilized, results in

    twins

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    Luteal Phase

    After ovulation, the ruptured follicle collapses,granulosa cells enlarge, and along with internalthecal cells, form the corpus luteum

    The corpus luteum secretes progesterone and

    estrogen If pregnancy does not occur, the corpus luteum

    degenerates in 10 days, leaving a scar (corpusalbicans)

    If pregnancy does occur, the corpus luteum produceshormones until the placenta takes over that role (atabout 3 months)

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    Uterine (Menstrual) Cycle

    Series of cyclic changes that the uterineendometrium goes through each month in responseto ovarian hormones in the blood

    : Menstrual phase Days 1-5

    uterus sheds all but the deepest part of the endometrium

    Days 6-14: Proliferative (preovulatory) phaseendometrium rebuilds itself

    Days 15-28: Secretory (postovulatory) phase

    endometrium prepares for implantation of theembryo

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    Endometrium

    Has numerous uterine glands that change in length

    as the endometrial thickness changes

    Stratum functionalis:

    Undergoes cyclic changes in response to ovarian hormones

    Is shed during menstruation

    Stratum basalis:

    Forms a new functionalis after menstruation ends

    Does not respond to ovarian hormones

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    Proliferative phase

    Duration: 2 weeks

    Thickness: 0.5mm 5mm

    Under the influence of estrogens from the developing

    follicle, the endometrium increases rapidly in thickness

    from the fifth to the fourteenth days of the menstrual

    cycle.

    As the thickness increases, the uterine glands are

    drawn out so that they lengthen, but they do notbecome convoluted or secrete to any degree. These

    endometrial changes are also called the preovulatory or

    follicular phase of the cycle.

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    Secretory phase

    Duration: 2 weeks

    Thickness: 5-6mm After ovulation, the endometrium becomes more

    highly vascularized and slightly edematous underthe influence of estrogen and progesterone from

    the corpus luteum. The glands become coiled and tortuous, and they

    begin to secrete a clear fluid. Consequently, thisphase of the cycle is called the secretory or luteal

    phase. Late in the luteal phase, the endometrium, like the

    anterior pituitary, produces prolactin, but thefunction of this endometrial prolactin is unknown.

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    Menses

    If fertilization does not occur, progesterone levels fall,depriving the endometrium of hormonal support

    Spiral arteries kink and go into spasms and endometrialcells begin to die

    The functional layer begins to digest itself

    Spiral arteries constrict one final time then suddenlyrelax and open wide The rush of blood fragments weakened capillary beds

    and the functional layer sloughs Nonclotting menstrual blood mainly comes from artery

    (75%) Interval: 24-35 days (28 days). duration: 2-6 days. the

    first day of menstrual bleeding is consideredy by day 1 Shedding: 30-50 ml

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    Menstruation

    Menstrual blood composition

    is predominantly arterial, with only 25% of theblood being of venous origin. It contains tissuedebris, prostaglandins, and relatively large amountsof fibrinolysin from endometrial tissue. Thefibrinolysin lyses clot, so that menstrual blood doesnot normally contain clots unless the flow isexcessive.

    The usual duration: 3-5 days, but flows as short as 1day and as long as 8 days can occur in normal women.

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    Menstruation

    The amount of blood lost may range normally

    slight spotting to 80 mL; the average amount lost

    is 30 mL.

    Loss of more than 80 mL is abnormal. Obviously,

    The amount of flow can be affected by various

    factors, including the thickness of the

    endometrium, medication, and diseases that

    affect the clotting mechanism. After

    menstruation, a new endometfrom rium

    regenerates from the stratum basale.

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    Menses (Cont.) When the corpus luteum regresses, hormonal

    support for the endometrium is withdrawn.

    The endometrium becomes thinner, which adds tothe coiling of the spiral arteries. Foci of necrosis

    appear in the endometrium, and these coalesce. There is in addition spasm and then necrosis of the

    walls of the spiral arteries, leading to spottyhemorrhages that become confluent and produce

    the menstrual flow.

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    Menses (Cont.)

    The vasospasm is probably produced by locally

    released prostaglandins. There are large

    quantities of prostaglandins in the secretory

    endometrium and in menstrual blood, and

    infusions of PGF2 produce endometrial necrosisand bleeding.

    One theory of the onset of menstruation holds

    that in necrotic endometrial cells, lysosomalmembranes break down, with the release of

    enzymes that foster the formation of

    prostaglandins from cellular phospholipids.

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    Changes of other genital organs

    Cervix

    During follicular phase estrogen causes mucus to be

    thin,clear, watery and the the midcycle a drop can be

    stretched into a long, thin thread that may be 8-12cm or more in length. In addition, it dries in an

    arborizing, fern-like pattern

    During luteal phase progesterone causes mucus to

    be thick, opaque, tenacious and cellular and loss of

    ability to form fern like appearance.

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    Changes of other genital organs

    Cyclic changes in the vagina

    Under the influence of estrogens, the vaginal

    epithelium becomes cornified,

    Under the influence of progesterone, a thick

    mucus is secreted, and the epithelium proliferates

    and becomes infiltrated with leukocytes.

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    Changes of other genital organs

    Cyclic changes in the breast Estrogens cause proliferation of mammary ducts.

    progesterone causes growth of lobules and alveoli.

    The breast swelling, tenderness, and painexperienced by many women during the 10 days

    preceding menstruation are probably due to

    distention of the ducts, hyperemia, and edema of

    the interstitial tissue of the breast. All these changesregress, along with the symptoms, during

    menstruation.

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    Establishing the Ovarian Cycle

    During childhood, ovaries grow and secrete

    small amounts of estrogens that inhibit the

    hypothalamic release of GnRH

    As puberty nears, GnRH is released; FSH and

    LH are released by the pituitary, which act on

    the ovaries

    These events continue until an adult cyclic

    pattern is achieved and menarche occurs

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    Hormonal Interactions During the Ovarian

    Cycle

    Day 1 GnRH stimulates the release of FSH and LH

    FSH and LH stimulate follicle growth and maturation, and low-level estrogen release

    Rising estrogen levels: Inhibit the release of FSH and LH

    Estrogen levels increase and high estrogen levels have apositive feedback effect on the pituitary, causing a suddensurge of LH

    The LH spike stimulates the primary oocyte to completemeiosis I, and the secondary oocyte continues on tometaphase II

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    Hormonal Interactions During the Ovarian

    Cycle

    Day 14 LH triggers ovulation

    LH transforms the ruptured follicle into a corpus

    luteum, which produces inhibin, progesterone, and

    estrogen These hormones shut off FSH and LH release and

    declining LH ends luteal activity

    Days 26-28 decline of the ovarian hormones

    Ends the blockade of FSH and LH

    The cycle starts anew

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    Summary of hormonal control of the cycle

    In an important sense, regression of the corpus luteum

    (luteolysis) starting 3-4 days before menses is the key to themenstrual cycle. PGF2 appears to be a physiologic luteolysin,

    but this prostaglandin is only active when endothelial cells

    producing ET-1 are present. Therefore it appears that at least in

    some species luteolysis is produced by the combined action ofPGF2

    and ET-1. In some domestic animals, oxytocin secreted by

    the corpus luteum appears to exert a local luteolytic effect,

    possibly by causing the release of prostaglandins. Once

    luteolysis begins, the estrogen and progesterone levels fall andthe secretion of FSH and LH increases. A new crop of follicles

    develops to start a new cycle

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    Menstrual Abnormalities

    Anovulatory cycle

    Amenorrhea

    Primary amenorrhea: period never occurs

    Secondary amenorrhea stop of the cycle after normal

    periods have occurred. Menorrahgia: excessive bleeding during

    menstruation

    Hypomenorrhea: scanty or little bleeding

    Metrorrahgia: bleeding between cycles.

    Oligomenorrhea: reduced frequency of the periods.