Endometriosis pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
The exact [[pathogenesis]] of [[endometriosis]] is not clear | 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 [[Endometrium|endometrial tissue]] outside the [[uterine cavity]]. [[Immunological|Immunologic]] factors and [[genetic]] factors are also thought to play a role in the pathogenesis of [[endometriosis]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
| Line 32: | Line 32: | ||
====Invasion and growth of the endometrial cells==== | ====Invasion and growth of the endometrial cells==== | ||
*The [[Endometrium|endometrial]] glandular cells are involved in the process of invasion.<ref name="pmid27424048">{{cite journal| author=Smarr MM, Kannan K, Buck Louis GM| title=Endocrine disrupting chemicals and endometriosis. | journal=Fertil Steril | year= 2016 | volume= 106 | issue= 4 | pages= 959-66 | pmid=27424048 | doi=10.1016/j.fertnstert.2016.06.034 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27424048 }} </ref> | *The [[Endometrium|endometrial]] glandular cells are involved in the process of invasion.<ref name="pmid27424048">{{cite journal| author=Smarr MM, Kannan K, Buck Louis GM| title=Endocrine disrupting chemicals and endometriosis. | journal=Fertil Steril | year= 2016 | volume= 106 | issue= 4 | pages= 959-66 | pmid=27424048 | doi=10.1016/j.fertnstert.2016.06.034 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27424048 }} </ref> | ||
*Degradation of the [[extracellular matrix]] due to the increased [[proteolytic]] activity allows | *Degradation of the [[extracellular matrix]] due to the increased [[proteolytic]] activity allows for invasion of the [[Endometrium|endometrial]] cells. | ||
*Numerous [[Proteases|metalloproteases]] and [[plasmin]] | *Numerous [[Proteases|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==== | ====Proliferation of the endometrial cells==== | ||
*The functional [[endometrium]] in the [[uterine cavity]] proliferates in response to | *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]].<ref name="pmid28109841">{{cite journal| author=Patel S| title=Disruption of aromatase homeostasis as the cause of a multiplicity of ailments: A comprehensive review. | journal=J Steroid Biochem Mol Biol | year= 2017 | volume= 168 | issue= | pages= 19-25 | pmid=28109841 | doi=10.1016/j.jsbmb.2017.01.009 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28109841 }} </ref> | ||
*[[Endometrial]] cells in patients with [[endometriosis]] have increased levels of [[aromatase]], leading to increased [[estrogen]] levels, resulting in excess proliferation. | *[[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. | *[[Endometrial]] cells also have resistance to [[progesterone]] which controls the [[proliferation]] of the endometrial cells. [[Progesterone]] resistance results in uncontrolled proliferation. | ||
Latest revision as of 12:11, 17 August 2017
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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
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.
Pathophysiology
Pathogenesis
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:[1][2][3][4][5]
- 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.[6]
- 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
- This theory proposes that endometrial tissue arises from the cells remaining from Müllerian 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 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.[7]
- 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.[8]
- 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.[9]
- Other common sites affected by endometriosis 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[10]
- Vagina
- Vulva
- Rectosigmoid[11]
- Anterior abdominal wall[12]
- Surgical scars[13]
- Urinary bladder
- Kidney[14]
- Lungs
- 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 development of endometriosis.[15][16]
- 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.
Associated Conditions
Endometriosis is associated with an increased risk of developing ovarian cancer.[17][18]
Gross Pathology
- 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.
Microscopic Pathology
- Microscopy of 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.
- ↑ Greene AD, Lang SA, Kendziorski JA, Sroga-Rios JM, Herzog TJ, Burns KA (2016). "Endometriosis: where are we and where are we going?". Reproduction. 152 (3): R63–78. doi:10.1530/REP-16-0052. PMC 4958554. PMID 27165051.
- ↑ Nothnick W, Alali Z (2016). "Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment". F1000Res. 5. doi:10.12688/f1000research.7504.1. PMC 4760268. PMID 26949527.
- ↑ Begum T, Chowdhury SR (2013). "Aetiology and pathogenesis of endometriosis - a review". Mymensingh Med J. 22 (1): 218–21. PMID 23416836.
- ↑ Benagiano G, Habiba M, Brosens I (2012). "The pathophysiology of uterine adenomyosis: an update". Fertil Steril. 98 (3): 572–9. doi:10.1016/j.fertnstert.2012.06.044. PMID 22819188.
- ↑ Templeman C (2009). "Adolescent endometriosis". Obstet Gynecol Clin North Am. 36 (1): 177–85. doi:10.1016/j.ogc.2008.12.005. PMID 19344855.
- ↑ Smarr MM, Kannan K, Buck Louis GM (2016). "Endocrine disrupting chemicals and endometriosis". Fertil Steril. 106 (4): 959–66. doi:10.1016/j.fertnstert.2016.06.034. PMID 27424048.
- ↑ Patel S (2017). "Disruption of aromatase homeostasis as the cause of a multiplicity of ailments: A comprehensive review". J Steroid Biochem Mol Biol. 168: 19–25. doi:10.1016/j.jsbmb.2017.01.009. PMID 28109841.
- ↑ Fritel X (2007). "[Endometriosis anatomoclinical entities]". J Gynecol Obstet Biol Reprod (Paris). 36 (2): 113–8. doi:10.1016/j.jgyn.2006.12.003. PMID 17275210.
- ↑ Park HM, Lee SS, Eom DW, Kang GH, Yi SW, Sohn WS (2009). "Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix: a case report". J Korean Med Sci. 24 (4): 767–71. doi:10.3346/jkms.2009.24.4.767. PMC 2719211. PMID 19654969.
- ↑ Hernández-Ramírez DA, Cravioto-Villanueva A, Barragan-Rincón A (2008). "[Rectal endometriosis: entity difficult to diagnose.]". Rev Gastroenterol Mex. 73 (3): 159–62. PMID 19671503.
- ↑ Collins AM, Power KT, Gaughan B, Hill AD, Kneafsey B (2009). "Abdominal wall reconstruction for a large caesarean scar endometrioma". Surgeon. 7 (4): 252–3. PMID 19736896.
- ↑ Chung MK, Jarnagin B (2009). "Early identification of interstitial cystitis may avoid unnecessary hysterectomy". JSLS. 13 (3): 350–7. PMC 3015962. PMID 19793476.
- ↑ Dirim A, Celikkaya S, Aygun C, Caylak B (2009). "Renal endometriosis presenting with a giant subcapsular hematoma: case report". Fertil Steril. 92 (1): 391.e5–7. doi:10.1016/j.fertnstert.2009.04.013. PMID 19476941.
- ↑ Fan W, Huang Z, Xiao Z, Li S, Ma Q (2016). "The cytochrome P4501A1 gene polymorphisms and endometriosis: a meta-analysis". J Assist Reprod Genet. 33 (10): 1373–1383. doi:10.1007/s10815-016-0783-4. PMC 5065559. PMID 27525656.
- ↑ Blakemore J, Naftolin F (2016). "Aromatase: Contributions to Physiology and Disease in Women and Men". Physiology (Bethesda). 31 (4): 258–69. doi:10.1152/physiol.00054.2015. PMID 27252161.
- ↑ Thomsen LH, Schnack TH, Buchardi K, Hummelshoj L, Missmer SA, Forman A; et al. (2017). "Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review". Acta Obstet Gynecol Scand. 96 (6): 761–778. doi:10.1111/aogs.13010. PMID 27565819.
- ↑ Lassus H, Pasanen A, Bützow R (2015). "[Is endometriosis a premalignant condition to ovarian carcinoma?]". Duodecim. 131 (19): 1777–84. PMID 26638662.