Endometriosis pathophysiology On the Web
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The exact pathogenesis of endometriosis is not clear; several theories have been set forth. The Sampson theory of retrograde menstruation, the coelomic metaplasia theory, and the lymphatic and vascular dissemination theory explain the implantation and invasion of the endometrial tissue outside the uterine cavity. Immunologic factors and genetic factors are also thought to play a role in the pathogenesis of endometriosis.
Translocation of the endometrial cells
The exact pathogenesis of endometriosis is still unknown. However, several theories have been put forward to explain the presence of viable and hormonally active endometrium outside the uterine cavity. These proposed theories are:
- Sampson's theory of retrograde menstruation
- This 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 this theory include the higher risk of developing endometriosis in patients with cervical stenosis and congenital outflow obstructions which result in a greater retrograde efflux, resulting in the implantation of endometrial tissue in the peritoneal cavity.
- This theory, however, doesn't explain the disease process in premenarcheal girls and newborns.
- Coelomic metaplasia theory
- This theory postulates that endometriosis is a result of metaplasia of the cells lining the visceral and parietal 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
- The stem cell theory:
Implantation of the endometrial cells
- The presence of endometrial cells alone outside the endometrial tissue is not endometriosis. The translocated endometrial cells must attach to the surrounding tissues, survive immune defense, and be affected by hormonal changes (estrogen). This is facilitated by various factors that influence the disease process:
- The endometrial stromal cells are essential for the attachment of the endometrial cells to the surrounding tissue.
- Ectopic endometrial cells 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.
- Aberrant integrin expression has 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 for invasion of the endometrial cells.
- Numerous metalloproteases and plasmin facilitate the degradation of the extracellular matrix and the 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 increased estrogen levels. The estrogen levels are dependent on the aromatase activity which catalyzes the conversion of ovarian androstenedione into estrone.
- Endometrial cells in patients with endometriosis have increased levels of aromatase, leading to increased estrogen levels, resulting in excess proliferation.
- Endometrial cells also have resistance to progesterone which controls the proliferation of the endometrial cells. Progesterone resistance results in uncontrolled proliferation.
- The reduction of excess estrogen and resistance to progesterone forms the basic principles 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 by endometriosis include:
- Less common sites affected include:
- 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 development of endometriosis.
- Polymorphisms in genes coding for the cytokines and toll-like receptors are also described to increase the risk of endometriosis.
- Postive family history of endometriosis in a 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.
- The gross appearance of the endometriosis lesions depends on the site, activity, day of the menstrual cycle, duration of the disease, and the presence of fibrosis.
- On laparoscopy, 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 called "chocolate cyst."
- Extensive endometriosis can result in fibrosis of the pelvic structures which can be visualized on abdominal laparoscopy.
- Microscopy of the biopsy tissue will demonstrate the presence of the endometrial stromal cells and glandular cells.
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