Uterus Flashcards
What does the presence of plasma cells (B cells) indicate on an EMB and what is the frequency?
Chronic endometritis, present in 10% biopsies done for AUB
When does implantation occur?
5-7 days after ovulation
What are the 3 cytokines expressed by the endometrium during implantation?
CSF-1, IL-1, LIF
What does the blastocyst express during implantation?
Heparin binding EGF (HB-EGF)
What are integrins?
Cell surface receptors involved in cell-cell and cell-matrix binding
Integrin expression is temporally related to implantation
What the important integrins found during implantation?
alpha-5, beta-6 integrin
What happens to NK cell concentration during implantation?
Increases
Define AUB?
Menstrual flow outside of normal volume (80cc), duration (5d), regularity or frequency (q21-35d)
What is Reeds Syndrome?
- Rare inherited condition characterized by multiple cutaneous leiomyomas and, in women, uterine leiomyomas.
- Predisposes for renal cell cancer, an association denominated hereditary leiomyomatosis and renal cell cancer
- Increased risk of uterine leiomyosarcoma
What is the most common cause of AUB?
Fibroids
What is the mechanism of growth of fibroids?
TGF-β dysregulation
Describe the onset of menses
Instead of vascular events, the new model of the initiation of menstruation is an enzymatic autodigestion of the functional layer of the endometrium and its subsurface capillary plexus
Describe cessation events of menses
Coagulation mechanisms, local vasoconstriction, and re-epithelialization -> homeostasis
What are the embryological origins of the kidneys?
Metanephric
What are the embryological origins of the Wolffian ducts?
Mesonephric
What are the embryological origins of the Mullerian ducts?
Paramesonephric
What is the most common uterine anomaly associated with RPL?
Septum
When is canalization of the vagina complete?
22 weeks gestation
Starts around 18 weeks gestation
Which is the uterine anomaly associated with poorest reproductive outcome?
Septum
What is the risk of pregnancy loss associated with a uterine septum?
LBR after getting it fixed? PTD? IUFD?
65% risk of pregnancy loss
LBR - 80%
PTD - 5%
IUFD - 15%
Unicornuate uterus
Risk of pregnancy loss?
breakdown by trimester? IUFD? Ectopic?
Risk of PTD?
other risk?
50% risk of pregnancy loss
25% 1st trimester SAB
10% 2nd trimester SAB
10% IUFD
5% Ectopic
PTD - 20%
Other - breech
What is the risk of pregnancy loss associated with a uterine didelphys?
40% risk of pregnancy loss
What is the risk of pregnancy loss associated with a bicornuate uterus?
30-40% risk of pregnancy loss
When does the ambisexual period of mullerian development occur and what is it?
Up to 8 weeks and is the period when both ducts co-exist
When do the paramesonephric ducts fuse?
~10 weeks; forms a T shape
Describe the risk of pregnancy loss associated with a unicornuate uterus in the first trimester?
24% risk of SAB in 1st trimester
Describe the risk of preterm delivery associated with a unicornuate uterus?
20% risk of PTD
Describe the risk of SAB in second trimester associated with a unicornuate uterus?
10% 2nd trimester SAB
Is an HSG able to differentiate between a bicornuate and septate uterus?
No
What is the hypothesized role played by Human leukocyte antigen G (HLA-G) in implantation?
Modulates cytokine secretion to control trophopblastic cell invasion and to maintain a local immunotolerance
What are the effects of P4 on implantation?
High P4 levels -> perivascular growth/decidualization -> suppression of prostaglandin, cytokine, MMP expression
What are the most abundant lymphoid cells in perimenstrual endometrium?
NK cells
Describe concentration of NK cells during proliferative and secretory phase?
- Few present in proliferative phase
- Comprise 15-25% of cells in stroma during secretory phase – possibly due to endometrial PRL production?
What are the proposed purpose of NK cells in implantation?
May have a role in initiating/maintaining decidualization, modulate trophoblast invasion & placentation
How is endometrial dating performed? (9 features)
Glandular Changes:
- Tortuosity
- Mitoses
- Orientation of nuclei (pseudostratfied or palisading)
- Subnuclear cytoplasmic vacuoles (first histologic sign of ovulation)
- Secretory exhaustion (luminal secretions)
Stromal Changes:
- Edema
- Mitoses
- Predecidua
- Granular Lymphocyte infiltrate
Describe the granular lymphocyte infiltrate component of endometrial dating
CD3+ T cells only 1-2% of lymphoid cells in endometrium and increase prior to menstruation
Ratio of CD4 (helper-) / CD8 (cytotoxic-T cells) in endometrium is reversed compared w/ peripheral blood
CD8 cells active during proliferative phase, diminished in secretory phase
Few B cells and plasma cells present
When does prostaglandin content reach its highest levels and what are the specific prostaglandins observed?
Prostaglandin content (PGF2a/PGE2) in secretory endometrium reaches highest levels at menstruation
Name the cell types seen in the healthy endometrium that are known to vary by the menstrual cycle.
Macrophages, neutrophils and NK cells
Describe the features of B and T cells
Part of adaptive immunity that are activated by specific antigen
Rate of pregnancy loss due to bicornuate uterus
30-40%
Progesterone effect on endometrium (5)
- Arrest of glandular proliferation → small inactive glands
- Pseudosecretion
- Stromal hyperplasia
- Decidualized strong with granulocytes and thin sinusoidal blood vessels
- Atrophy
Layers of endometrium (2)
- Functionalis (upper ⅔, responsive to hormones, sheds)
- Basalis (lower ⅓, grows rapidly during proliferation phase)
Dating endometrium:
When do you see prominent spiral arteries? due to what?
and what happens next?
Days 21-22, due to P4
Inc in edema between stromal cells, stromal cell hypertrophy with accumulation of cytoplasmic eosinophilia (predecidual change) and resurgence of stromal mitoses
How does withdrawal of estrogen and progesterone cause apoptosis?
Enzymatic autodigestion - With waning of E and P, lysosome enzymes released into the cytoplasm -> enzymes digest their cellular constraints -> release of prostaglandins, extravasation of red blood cells, tissue necrosis, and vascular thrombosis
Menses – what causes bleeding to stop?
- result of the combined effects of prolonged vasoconstriction of the radial arteries and the spiral arteries in the basalis, tissue collapse, vascular stasis, and estrogen-induced “healing.”
- Thrombin generation in the basal endometrium in response to extravasation of blood is essential for hemostasis.
(Thrombin promotes the generation of fibrin, the activation of platelets and clotting cofactors, and angiogenesis.)
How do NSAIDs help AUB? And by how much?
Inhibit prostaglandin synthesis
by 20-40%
18 yo presents with menorrhagia. Testing would include:
- aPTT
- ristocetin factor
- vWF
Most common inherited bleeding disorder among women with menorrhagia & prevalence?
vWD - 13%
Therapeutic estrogen for AUB has what effect on endometrium? and at high dose?
- Stimulates endometrial re-epithelialization and proliferation and stabilizes lysosomal enzymes
- High-dose estrogen therapy also stimulates clotting at the capillary level.
What progestin drug has most potent effect on endometrium
Norethindrone
What part of menstrual cycle determines cycle intervals and frequency?
Follicular phase
