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+
Physiology Of
Menstruation
Dr Anusha Rao P
PGY2 (OBG)
+
Menstruation is a visible manifestation of cyclic, physiologic
uterine bleeding due to shedding of the endometrium follo...
+
+HORMONES FOLLICULAR
PHASE
OVULATION LUTEAL PHASE
DAILY
PRODUCTION
(ug)
OESTRADIOL
PROGESTERONE
50
2 - 3
150-300 100
20 -3...
+
+
 Menstrual cycle can be explained in two cycles which occur
concurrently
• The ovarian cycle and
• The uterine cycle
 ...
+
THE OVARIAN
CYCLE
+ Follicular
phase
+
+
Primordial follicle
 Originate in the Endoderm
 Migrate to the genital ridge at 5-6weeks
 Maximum at 16 – 20 wks : 6 ...
+
The primordial follicle is nongrowing and consists of an oocyte,
arrested in the diplotene stage of meiotic prophase, su...
+
 The initial recruitment and growth of the primordial follicles is gonadotropin
independent and affects a cohort over s...
+
Gap junctions composed of channels formed by arrangement of
proteins known as Connexins –
 up regulated and kept open b...
+
The Pre antral Follicle
 Oocyte enlarges and is surrounded by a membrane, the zona
pellucida.
 The granulosa cells und...
+
 The granulosa cells of the preantral follicle synthesizes all 3 classes of
steroids
 Estrogens are produced more than...
+
FSH both
 initiates steroidogenesis (estrogen production) in granulosa
cells and
 stimulates granulosa cell growth and...
+
+
The Antral Follicle
 Under the influence of estrogen and
FSH, there is an increase in the
production of follicular flui...
+
P45OC17
P450arom
+
The Two-Cell,
Two-Gonadotropin System
 The aromatase activity of the granulosa cells is more than
thecal cells.
 In hu...
+
 As the follicle emerges, the theca cells are characterized by their
expression of P450c17, the enzyme step that is rat...
+
Selection of the Dominant Follicle
 The process of conversion of a single follicle to a estrogen
dominant follicle depe...
+
 The first event in the process of atresia is a reduction in FSH
receptors in the granulosa layer
 A wave of atresia a...
+
 Lower GnRH pulse frequencies favor FSH secretion, and
higher GnRH pulse frequencies favor LH secretion.
 Low levels o...
+
+
 High levels of estrogen induce the LH surge at midcycle, and
high steady levels of estrogen lead to sustained elevated...
+
Inhibin, Activin, and Follistatin
 This family of peptides is synthesized by granulosa cells in
response to FSH and sec...
+
 Inhibin
 Blocks the synthesis and secretion of FSH,
 Prevent the up-regulation of GnRH receptors by GnRH,
 Reduce t...
+
The Preovulatory Follicle
 Granulosa cells in the preovulatory follicle
enlarge and acquire lipid inclusions
 And thec...
+
 The onset of the LH surge occurs when the peak levels of
estradiol are achieved.
 In providing the ovulatory stimulus...
+
 After adequate estrogen priming, progesterone facilitates the
positive feedback response.
 And in the presence of sub...
+
 Progesterone at midcycle is significantly responsible for the
FSH surge.
 Thus ensures completion of FSH action on th...
+
Ovulation
+
 A threshold of LH concentration must be maintained for at least
14 to 27 hours in order for full maturation of the ooc...
+
LH, FSH, Progesterone, growth factors
Plasminogen activator synthesis (granulosa &theca cells)
Plasminogen Plasmin
Colla...
+
+
 Estradiol levels plunge as LH reaches its peak. This may be a
consequence of LH down-regulation of its own receptors o...
+
LUTEAL
PHASE
+
 Luteinization and the corpus luteum:
granulosa cells increase in size and assume a characteristic
vacuolated appearanc...
+
 Angiopoietin-1 binds to the endothelial Tie-2 receptor & inc.
expr. Of VEGF + LH -> Angiogenesis
 Angiopoietin-2, lea...
+
 The leukocytes in the corpus luteum secrete cytolytic
enzymes, prostaglandins, and growth factors involved in
angiogen...
+
 Luteal cell population is composed of two distinct cell types,
large and small cells.
 Large cells are derived from g...
+
 The corpus luteum rapidly declines 9 to 11 days after ovulation.
 The regression of luteal cells is induced by the es...
+
 Prostaglandin F2Alpha stimulates the synthesis of endothelin
 Endothelin-1
 inhibits luteal steroidogenesis,
 stimu...
+
+
The Luteal-
Follicular
Transition
+
 The demise of the corpus luteum results in a nadir in the circulating levels
of estradiol, progesterone, and inhibin.
...
+
+HORMONES FOLLICULAR
PHASE
OVULATION LUTEAL PHASE
DAILY
PRODUCTION
(ug)
OESTRADIOL
PROGESTERONE
50
2 - 3
150-300 100
20 -3...
+
 From the midluteal peak to menses,
 there is a 4.5-fold increase in LH pulse frequency
 FSH pulse frequency increase...
+
UTERINE CYCLE
+
 The changes in the endometrium will be discussed in five
phases:
(1) The menstrual endometrium
(2) The proliferative p...
+
+
The Proliferative Phase
 The glands :
 narrow and tubular, lined by low columnar epithelium cells.
 Mitoses
 Pseudos...
+ THE
PROLIFERATIVE
PHASE
+
 All of the tissue components demonstrate proliferation, which peaks on days
8-10 of the cycle, corresponding to peak e...
+
 The endometrium grows from approximately 0.5 mm to 3.5 to
5.0 mm in height
 Restoration of tissue constituents has be...
+ THE
SECRETOR
Y PHASE
+
 The endometrium now demonstrates a combined reaction to
estrogen and progesterone activity.
 Epithelial proliferation...
+
 Tissue components continue to display growth, but confinement in a fixed structure leads
to progressive tortuosity of ...
+
IMPLANTATION
PHASE
+
 By 13 days postovulation, the endometrium has differentiated into three
distinct zones.
 1/4th of the tissue is the u...
+
 The subepithelial capillaries and spiral vessels are engorged
 At the time of implantation, on days 21-22 of the cycl...
+
ENDOMETRIAL
BREAKDOWN
+
 In the absence of fertilization, implantation, and the consequent
lack of hCG from the trophoblast, the fixed lifespan...
+
 The following vascular sequence occurs
 With shrinkage of height, blood flow within the spiral vessels
diminishes, ve...
+
 White cells migrate through capillary walls, extending throughout the
stroma.
 During arteriolar vasomotor changes, r...
+
 In the first half of the secretory phase, acid phosphatase and
potent lytic enzymes are confined to lysosomes, stabili...
+
+
 Endometrial tissue breakdown also involves a family of
enzymes, matrix metalloproteinases
 The metalloproteinases inc...
+
 Progesterone withdrawal from endometrial cells induces matrix
metalloproteinase secretion.
 In a nonpregnant cycle, m...
+
+
 Progesterone withdrawal is associated with an increase in
VEGF receptor concentrations in the stromal cells.
 Althoug...
+
 Eventually,Leakage occurs as a result of diapedesis, and finally,
interstitial hemorrhage occurs due to breaks in supe...
+
 PAI-1 exerts an important restraining action on fibrinolysis and
proteolytic activity.
 Blood loss is also controlled...
+
 Thrombin generation in the basal endometrium in response to
extravasation of blood is essential for hemostasis.
 The ...
+
 A natural cleavage point exists between basalis and
spongiosum, and, once breached, the loose, vascular,
edematous str...
+
 Within 13 hours, the endometrial height shrinks from 4 mm to
1.25 mm.
 Menstrual flow stops as a result of the combin...
+
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Physiology of menstruation

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Physiology of menstruation

  1. 1. + Physiology Of Menstruation Dr Anusha Rao P PGY2 (OBG)
  2. 2. + Menstruation is a visible manifestation of cyclic, physiologic uterine bleeding due to shedding of the endometrium following invisible interplay of hormones mainly through H-P-O axis. Normal limits:  Frequency: 24-38 days  Regularity: +/- 2-20 days  Duration: 4-8 days  Volume: 5-80 mL
  3. 3. +
  4. 4. +HORMONES FOLLICULAR PHASE OVULATION LUTEAL PHASE DAILY PRODUCTION (ug) OESTRADIOL PROGESTERONE 50 2 - 3 150-300 100 20 -30 SERUM VALUES OESTRADIOL (pg/ml) PROGESTERONE (ng/ml) FSH (mIU/ml) LH (mIU/ml) 50 <1 10 5 300- 600 15- 20 60 150-200 >5 10 5 DAILY EXCRETION TOTAL OESTROGEN (ug) PREGNANEDIOL (mg) 10-25 <1 35- 100 25-75 3-6
  5. 5. +
  6. 6. +  Menstrual cycle can be explained in two cycles which occur concurrently • The ovarian cycle and • The uterine cycle  The Ovarian Cycle consists of  The follicular phase and  The luteal phase  The Uterine Cycle consists of  The proliferative phase and  The secretory phase
  7. 7. + THE OVARIAN CYCLE
  8. 8. + Follicular phase
  9. 9. +
  10. 10. + Primordial follicle  Originate in the Endoderm  Migrate to the genital ridge at 5-6weeks  Maximum at 16 – 20 wks : 6 – 7 million  At Birth : 2 million  At Pubery : 0.3 to 0.5 million  Only 400 – 500 follicles ovulate during a woman’s reproductive years.
  11. 11. + The primordial follicle is nongrowing and consists of an oocyte, arrested in the diplotene stage of meiotic prophase, surrounded by a single layer of spindle-shaped granulosa cells.
  12. 12. +  The initial recruitment and growth of the primordial follicles is gonadotropin independent and affects a cohort over several months  The total duration of time to achieve pre ovulatory status is approximately 85 days  First visible signs of development are  Increase in the size of oocyte  granulosa cells becoming cuboidal
  13. 13. + Gap junctions composed of channels formed by arrangement of proteins known as Connexins –  up regulated and kept open by FSH and  down regulated and closed by LH
  14. 14. + The Pre antral Follicle  Oocyte enlarges and is surrounded by a membrane, the zona pellucida.  The granulosa cells undergo a multilayer proliferation as the theca layer continues to organize from the surrounding stroma.
  15. 15. +  The granulosa cells of the preantral follicle synthesizes all 3 classes of steroids  Estrogens are produced more than androgens or progestins  An aromatase enzyme system converts androgens to estrogens and is a factor limiting ovarian estrogen production.  Aromatization is induced or activated through the action of FSH.
  16. 16. + FSH both  initiates steroidogenesis (estrogen production) in granulosa cells and  stimulates granulosa cell growth and proliferation
  17. 17. +
  18. 18. + The Antral Follicle  Under the influence of estrogen and FSH, there is an increase in the production of follicular fluid.  Oocyte and the surrounding granulosa cells are nurtured in this follicular fluid  The granulosa cells surrounding the oocyte are now designated the cumulus oophorus
  19. 19. + P45OC17 P450arom
  20. 20. + The Two-Cell, Two-Gonadotropin System  The aromatase activity of the granulosa cells is more than thecal cells.  In human preantral and antral follicles,  LH receptors are present only on the theca cells and  FSH receptors only on the granulosa  LH stimulates thecal cells to produce androgens that can then be converted, through FSH-induced aromatization, to estrogens in the granulosa cells.
  21. 21. +  As the follicle emerges, the theca cells are characterized by their expression of P450c17, the enzyme step that is rate limiting for the conversion of 21-carbon substrate to androgens.  Increasing expression of the aromatization system (P450arom) is a marker of increasing maturity of granulosa cells.  The presence of P450c17 only in theca cells and P450arom only in granulosa cells is an impressive evidence confirming the two-cell, two-gonadotropin explanation for estrogen production
  22. 22. + Selection of the Dominant Follicle  The process of conversion of a single follicle to a estrogen dominant follicle depends on  (1) a local interaction between estrogen and FSH within the follicle, :-positive feedback  (2) the effect of estrogen on pituitary secretion of FSH:- negative feedback.  Serves to withdraw gonadotropin support from the other less developed follicles.
  23. 23. +  The first event in the process of atresia is a reduction in FSH receptors in the granulosa layer  A wave of atresia among the lesser follicles, is seen to parallel the rise in estrogen.
  24. 24. +  Lower GnRH pulse frequencies favor FSH secretion, and higher GnRH pulse frequencies favor LH secretion.  Low levels of estrogen enhance FSH and LH synthesis and storage, have little effect on LH secretion, and inhibit FSH secretion.
  25. 25. +
  26. 26. +  High levels of estrogen induce the LH surge at midcycle, and high steady levels of estrogen lead to sustained elevated LH secretion.  Low levels of progesterone acting at the level of the pituitary gland enhance the LH response to GnRH and are responsible for the FSH surge at midcycle.  High levels of progesterone inhibit pituitary secretion of gonadotropins by inhibiting GnRH pulses at the level of the hypothalamus.
  27. 27. + Inhibin, Activin, and Follistatin  This family of peptides is synthesized by granulosa cells in response to FSH and secreted into the follicular fluid and ovarian venous effluent.  They are expressed in many tissues through out the body as autocrine-paracrine regulators.  Inhibin is an important inhibitor of FSH secretion.  Activin stimulates FSH release in the pituitary and augments FSH action in the ovary.  Follistatin suppresses FSH activity by binding to activin.
  28. 28. +  Inhibin  Blocks the synthesis and secretion of FSH,  Prevent the up-regulation of GnRH receptors by GnRH,  Reduce the number of GnRH receptors present,  At high concentrations, promote the intracellular degradation of gonadotropins.
  29. 29. + The Preovulatory Follicle  Granulosa cells in the preovulatory follicle enlarge and acquire lipid inclusions  And theca becomes vacuolated and richly vascular, giving the preovulatory follicle a hyperemic appearance.  The oocyte proceeds in meiosis, approaching completion of its reduction division.  Approaching maturity, the preovulatory follicle produces increasing amounts of estrogen.  Estrogen peaks approximately 24 to 36 hours prior to ovulation.
  30. 30. +  The onset of the LH surge occurs when the peak levels of estradiol are achieved.  In providing the ovulatory stimulus to the selected follicle, the LH surge seals the fate of the remaining follicles, with their lower estrogen and FSH content, by further increasing androgen superiority.  LH promotes luteinization of the granulosa in the dominant follicle, resulting in the production of progesterone
  31. 31. +  After adequate estrogen priming, progesterone facilitates the positive feedback response.  And in the presence of subthreshold levels of estradiol can induce a characteristic LH surge.  When administered before the estrogen stimulus, or in high doses (achieving a blood level greater than 2 ng/mL), progesterone blocks the midcycle LH surge.
  32. 32. +  Progesterone at midcycle is significantly responsible for the FSH surge.  Thus ensures completion of FSH action on the follicle, especially making sure that a full complement of LH receptors is in place in the granulosa layer.  As products of thecal tissue are androgens, the increase in stromal tissue in the late follicular phase is associated with a rise in androgen levels. - for atresia of lesser follicles and for libido enhancement
  33. 33. + Ovulation
  34. 34. +  A threshold of LH concentration must be maintained for at least 14 to 27 hours in order for full maturation of the oocyte to occur.  Usually the LH surge lasts 48 to 50 hours
  35. 35. + LH, FSH, Progesterone, growth factors Plasminogen activator synthesis (granulosa &theca cells) Plasminogen Plasmin Collagenase Disrupts follicular wall
  36. 36. +
  37. 37. +  Estradiol levels plunge as LH reaches its peak. This may be a consequence of LH down-regulation of its own receptors on the follicle.  Due to-  High LH causes supression of steroidogenesis  Low midcycle levels of progesterone exert an inhibitory action on further granulosa cell multiplication, and hence the drop in estrogen  Estrogen can exert an inhibitory effect on P450c17(aromatase enzyme)
  38. 38. + LUTEAL PHASE
  39. 39. +  Luteinization and the corpus luteum: granulosa cells increase in size and assume a characteristic vacuolated appearance associated with the accumulation of a yellow pigment , lutein.  theca lutein cells may differentiate from the surrounding theca and stroma to become part of the corpus luteum.
  40. 40. +  Angiopoietin-1 binds to the endothelial Tie-2 receptor & inc. expr. Of VEGF + LH -> Angiogenesis  Angiopoietin-2, leads to vascular breakdown that accompanies luteolysis.  Vascularization of the granulosa layer is essential to allow LDL- cholesterol to reach the luteal cells to provide sufficient substrate for progesterone.  By day 8 or 9 after ovulation, a peak of vascularization is reached, associated with peak levels of progesterone and estradiol in the blood.
  41. 41. +  The leukocytes in the corpus luteum secrete cytolytic enzymes, prostaglandins, and growth factors involved in angiogenesis, steroidogenesis, and luteolysis.  Endothelin-1 is a mediator of luteolysis
  42. 42. +  Luteal cell population is composed of two distinct cell types, large and small cells.  Large cells are derived from granulosa cells and the small cells from theca cells. The small cells are the most abundant.  Steroidogenesis takes place in the large cells,  Small cells contain LH and hCG receptors.  LH/hCG receptors are absent on the large cells,
  43. 43. +  The corpus luteum rapidly declines 9 to 11 days after ovulation.  The regression of luteal cells is induced by the estradiol produced by the corpus luteum.  This action of estrogen is mediated by nitric oxide.  The final signal for luteolysis, however, is prostaglandin F2 alpha, produced within the ovary in response to the locally synthesized luteal estrogen.
  44. 44. +  Prostaglandin F2Alpha stimulates the synthesis of endothelin  Endothelin-1  inhibits luteal steroidogenesis,  stimulates prostaglandin production in luteal cells.  stimulates the release of TNF Alpha,which induces apoptosis.
  45. 45. +
  46. 46. + The Luteal- Follicular Transition
  47. 47. +  The demise of the corpus luteum results in a nadir in the circulating levels of estradiol, progesterone, and inhibin.  The decrease in inhibin-A removes a suppressing influence on FSH secretion in the pituitary.  The decrease in estradiol and progesterone allows a progressive and rapid increase in the frequency of GnRH pulsatile secretion and a removal of the pituitary from negative feedback suppression.  The removal of inhibin-A and estradiol and increasing GnRH pulses combine to allow greater secretion of FSH compared with LH, with an increase in the frequency of the episodic secretion.  The increase in FSH is instrumental in rescuing approximately a 70-day- old group of ready follicles from atresia, allowing a dominant follicle to begin its emergence.
  48. 48. +
  49. 49. +HORMONES FOLLICULAR PHASE OVULATION LUTEAL PHASE DAILY PRODUCTION (ug) OESTRADIOL PROGESTERONE 50 2 - 3 150-300 100 20 -30 SERUM VALUES OESTRADIOL (pg/ml) PROGESTERONE (ng/ml) FSH (mIU/ml) LH (mIU/ml) 50 <1 10 5 300- 600 15- 20 60 150-200 >5 10 5 DAILY EXCRETION TOTAL OESTROGEN (ug) PREGNANEDIOL (mg) 10-25 <1 35- 100 25-75 3-6
  50. 50. +  From the midluteal peak to menses,  there is a 4.5-fold increase in LH pulse frequency  FSH pulse frequency increases 3.5-fold  The increase in FSH is, as noted, greater than that of LH.
  51. 51. + UTERINE CYCLE
  52. 52. +  The changes in the endometrium will be discussed in five phases: (1) The menstrual endometrium (2) The proliferative phase (3) The secretory phase (4) Preparation for implantation, and finally (5) The phase of endometrial breakdown.
  53. 53. +
  54. 54. + The Proliferative Phase  The glands :  narrow and tubular, lined by low columnar epithelium cells.  Mitoses  Pseudostratification  A continuous epithelial lining facing the endometrial cavity is formed.
  55. 55. + THE PROLIFERATIVE PHASE
  56. 56. +  All of the tissue components demonstrate proliferation, which peaks on days 8-10 of the cycle, corresponding to peak estradiol levels in the circulation and maximal estrogen receptor concentration in the endometrium  Changes are most intense in the functionalis layer in the upper two-thirds of the uterus, the usual site of blastocyst implantation.
  57. 57. +  The endometrium grows from approximately 0.5 mm to 3.5 to 5.0 mm in height  Restoration of tissue constituents has been achieved by estrogen-induced new growth as well as incorporation of ions, water, and amino acids.  An important feature of this estrogen-dominant phase of endometrial growth is the increase in ciliated and microvillous cells
  58. 58. + THE SECRETOR Y PHASE
  59. 59. +  The endometrium now demonstrates a combined reaction to estrogen and progesterone activity.  Epithelial proliferation ceases 3 days after ovulation.  Total endometrial height is fixed at roughly its preovulatory extent (5-6 mm) despite continued availability of estrogen. This limitation is due to :  Progesterone interference with estrogen receptor expression  stimulation of 17beta-hydroxysteroid dehydrogenase and sulfotransferase, which convert estradiol to estrone sulfate (which is rapidly excreted from the cell)
  60. 60. +  Tissue components continue to display growth, but confinement in a fixed structure leads to progressive tortuosity of glands and intensified coiling of the spiral vessels.  The first histologic sign that ovulation has occurred is the appearance of subnuclear intracytoplasmic glycogen vacuoles in the glandular epithelium on cycle days 17-18.  These structural alterations are soon followed by  - active secretion of glycoproteins and peptides into the endometrial cavity  -Transudation of plasma  -immunoglobulins obtained from the circulation  The peak secretory level is reached 7 days after the midcycle gonadotropin surge, coinciding with the time of blastocyst implantation
  61. 61. + IMPLANTATION PHASE
  62. 62. +  By 13 days postovulation, the endometrium has differentiated into three distinct zones.  1/4th of the tissue is the unchanged basalis, straight vessels and spindle- shaped stroma.  The midportion (approx 50% of the total) is the lace like stratum spongiosum,loose edematous stroma with tightly coiled spiral vessels and dilated glandular ribbons.  the superficial layer of the endometrium (about 25% of the height) called the stratum compactum, which has become large and polyhedral stromal cell, forming a compact, structurally sturdy layer.
  63. 63. +  The subepithelial capillaries and spiral vessels are engorged  At the time of implantation, on days 21-22 of the cycle, the predominant morphologic feature is edema of the endometrial stroma , due to inc in permeability under the influence of steroids
  64. 64. + ENDOMETRIAL BREAKDOWN
  65. 65. +  In the absence of fertilization, implantation, and the consequent lack of hCG from the trophoblast, the fixed lifespan of the corpus luteum is completed, and estrogen and progesterone levels wane.  The most prominent immediate effect of this hormone withdrawal is a modest shrinking of the tissue height and spiral arteriole vasomotor responses.
  66. 66. +  The following vascular sequence occurs  With shrinkage of height, blood flow within the spiral vessels diminishes, venous drainage is decreased, and vasodilation ensues.  Thereafter, the spiral arterioles undergo rhythmic vasoconstriction and relaxation.  Each successive spasm is more prolonged and profound, leading eventually to endometrial blanching.  Within the 24 hours immediately preceding menstruation, these reactions lead to endometrial ischemia and stasis.
  67. 67. +  White cells migrate through capillary walls, extending throughout the stroma.  During arteriolar vasomotor changes, red blood cells escape into the interstitial space. Thrombin-platelet plugs also appear in superficial vessels.  The prostaglandin content (PGF2 alpha and PGE2) in the secretory endometrium reaches its highest levels at the time of menstruation.  The vasoconstriction and myometrial contractions associated with the menstrual events are mediated by prostaglandins from perivascular cells and the potent vasoconstrictor endothelin-1, derived from stromal decidual cells.
  68. 68. +  In the first half of the secretory phase, acid phosphatase and potent lytic enzymes are confined to lysosomes, stabilized by progesterone, which are released with waning of it’s level.  These active enzymes will digest their cellular constraints, leading to the release of prostaglandins, extravasation of red blood cells, tissue necrosis, and vascular thrombosis
  69. 69. +
  70. 70. +  Endometrial tissue breakdown also involves a family of enzymes, matrix metalloproteinases  The metalloproteinases include  collagenases that degrade interstitial and basement membrane collagens;  gelatinases that further degrade collagens;  and stromelysins that degrade fibronectin, laminin, and glycoproteins
  71. 71. +  Progesterone withdrawal from endometrial cells induces matrix metalloproteinase secretion.  In a nonpregnant cycle, metalloproteinase expression is suppressed after menses by increasing estrogen levels.
  72. 72. +
  73. 73. +  Progesterone withdrawal is associated with an increase in VEGF receptor concentrations in the stromal cells.  Although the VEGF system is usually involved with angiogenesis, in this case these factors are involved in the preparation for menstrual bleeding, perhaps influencing the expression of matrix metalloproteinases.
  74. 74. +  Eventually,Leakage occurs as a result of diapedesis, and finally, interstitial hemorrhage occurs due to breaks in superficial arterioles and capillaries.  As ischemia and weakening progress, the continuous binding membrane is fragmented, and intercellular blood is extruded into the endometrial cavity.  New thrombin-platelet plugs form intravascularly upstream at the shedding surface, limiting blood loss.  Increased blood loss is a consequence of reduced platelet numbers and inadequate hemostatic plug formation.  Menstrual bleeding is influenced by activation of clotting and fibrinolysis
  75. 75. +  PAI-1 exerts an important restraining action on fibrinolysis and proteolytic activity.  Blood loss is also controlled by constriction of the spiral arteries, mediated by the perivascular cells, myofibroblasts that surround the spiral arteries.  Myofibroblasts respond to progesterone withdrawal by expressing prostaglandins and cytokines, causing cycling vasoconstriction and vasodilation
  76. 76. +  Thrombin generation in the basal endometrium in response to extravasation of blood is essential for hemostasis.  The basalis endometrium remains during menses, and repair takes place from this layer.  This endometrium is protected from the lytic enzymes in the menstrual fluid by a mucinous layer of carbohydrate products that are discharged from the glandular and stromal cells.
  77. 77. +  A natural cleavage point exists between basalis and spongiosum, and, once breached, the loose, vascular, edematous stroma of the spongiosum desquamates and collapses.  The process is initiated in the fundus and extends throughout the uterus.  In the end, the typical deflated, shallow, dense, menstrual endometrium results.
  78. 78. +  Within 13 hours, the endometrial height shrinks from 4 mm to 1.25 mm.  Menstrual flow stops as a result of the combined effects of  Prolonged vasoconstriction of the radial arteries and the spiral arteries in the basalis,  Tissue collapse,  Vascular stasis,  Estrogen-induced healing  In contrast to postpartum bleeding, myometrial contractions are not important for control of menstrual bleeding.
  79. 79. + THANK YOU

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