Endometriosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Overview
Pathophysiology
Pathogenesis
Translocation of the endometrial cells
The exact pathogenesis of endometriosis is still unknown, however several theories were put forward to explain the the presence the of viable and hormonally active endometrium outside the uterine cavity. The theories proposed include the following:[1]
- Sampson's theory of retrograde menstruation: The theory postulates that the viable endometrial tissue passes in a retrograde fashion via the fallopian tubes to reach the peritoneal cavity and subsequently implants onto the pelvic structures and organs.
- Factors favoring the theory include the higher risk of developing endometriosis in patients with cervical stenosis and congenital outflow obstructions which result in a greater retrograde efflux, and also the implantation of endometrial tissue in the peritoneal cavity resulted in the disease.
- This theory, however, doesn't explain the disease process in premenarchal girls and new borns.
- Coelomic metaplasia theory: This theory postulates that endometriosis is a result of metaplasia of the cells lining the visceral and abdominal peritoneum following various hormonal, environmental, or infectious stimuli. This theory is supported by the evidence that the abdominal, pelvic, and thoracic peritoneum, the Mullerian ducts, the germinal epithelium of the ovary and the endometrium are all derived from the coelomic wall epithelium explaining the occurrence of endometriosis at these sites.
- Embryonic rest theory: This theory proposes that endometrial tissue arises from the cells remaining from Mullerian duct migration during embryonic development, following estrogen stimulation.
- The stem cell theory: This theory is based on experimental evidence explaining the fact that the endometrial stem cells from the basalis layer and the bone marrow-derived stem cells can travel via the retrograde fashion or via the lymphatic or vascular system resulting in endometriosis.
Implantation of the endometrial cells
- The presence of endometrial cells alone outside the endometrial tissue doesn't cause endometriosis. The translocated endometrial cells must attach to the surrounding tissues, survive the immune defense and be receptive to the harmonal changes of estrogen. This is facilitated by various factors which influence the disease process:
- The endometrial stromal cells are essential for the attachment of the endometrial cells to the surrounding tissue.
- Eutopic endometrial in endometriosis are resistant to cell mediated immunity and have increased proliferative capacity.
- The ectopic endometrial cells have an increased aromatase expression leading to increased estrogen concentrations.
- Abberant integrin expression is also been described as a factor involved in the process of implantation.
Invasion and growth of the endometrial cells
- The endometrial glandular cells are involved in the process of invasion.
- Degradation of the extracellular matrix due to the increased proteolytic activity allows in the invasion of the endometrial cells.
- Numerous metalloproteases and plasmin help in the degradation of the extracellular matrix and in establishment of an endometrial lesion outside the uterine cavity.
Proliferation of the endometrial cells
- The functional endometrium in the uterine cavity proliferates in response to the increase in estrogen levels. The estrogen levels are dependent on the aromatase activity which catalyses the conversion of ovarian androstenedione into estrone.
- Endometrial cells in patients with endometriosis have increased levels in the aromatase levels leading to increased estrogen levels resulting in excess proliferation.
- The endometrial cells also have resistance to progesterone which controls the proliferation of the endometrial cells resting in uncontrolled proliferation.
- The reduction of excess estrogen and resistance to progesterone forms the basic principle for the medical therapy of endometriosis.
Commonly affected sites in endometriosis
- Endometriosis lesions commonly occur in the dependent areas with ovaries being the most common site.
- Other common sites affected include:
- Pelvic peritoneum lining the uterus
- Posterior cul-de-sac
- Round and broad ligaments of the uterus
- Lymph nodes
- Less common sites affected include:
- Cervix
- Vagina
- Vulva
- Rectosigmioid
- Anterior abdominal wall
- Surgical scars
- Urinary bladder
- Kidney
- Lung
- Arms
- Legs
- Urinary tract
Genetics
- Cell mediated immunity defenses and aromatase activity are essential for the growth of the translocated tissue. Polymorphisms in the genes coding for them are described in women with endometriosis explaining the genetic predisposition to develop endometriosis,
- Polymorphisms in the genes coding for the cytokines and toll like receptors are also described to increase the risk of endometriosis.
- Postive family history of endometriosis in first degree relative is associated with a six times higher risk of developing endometriosis.
- Heterogenicity of chromosome 17 and aneuploidy is described in patients with endometriosis.
Gross Pathology
- The gross appearance of the lesions depend on the site, activity, day of the menstrual cycle, duration of the disease, and the presence of fibrosis.
- On laproscopy, endometriosis affecting the pelvic organs appears as raised dark non hemorrhagic lesions. They can also appear brown, black, white, yellow, pink or clear lesions based on the amount of blood supply.
- Endometriosis of the ovary appears as a dark necrotic tissue and is coined as "chocolate cyst".
- Extensive endometriosis can result in fibrosis of the pelvic structures which can be visualized on abdominal laproscopy.
Microscopic Pathology
- Microscopy of the the biopsy tissue will demonstrate the presence of the endometrial stromal cells and glandular cells.
References
- ↑ Bulun, Serdar E. (2009). "Endometriosis". New England Journal of Medicine. 360 (3): 268–279. doi:10.1056/NEJMra0804690. ISSN 0028-4793.