pre-eclampsia

pre-eclampsia, a short and simplified explanation

1. Department of Pathophysiology Medical Faculty P. J. Šafarik University Košice Preeclampsia Nasim Badarna GM- 3 2015/2016

2. outlines Introduction Classification Etiology Epidemiology Risk factors Symptoms Complication Prevention Conclusion

3. Introduction Preeclampsia, first described >100 years ago, is a common pregnancy disorder known as one of the leading causes of maternal and infant mortality .   Preeclampsia is a dangerous complication that usually occurs in the  third trimester  of pregnancy and worsens over time, characterized by hypertension , proteinuria , and other systemic disturbances.

4. hypertension (onset > 20 weeks) + proteinuria OR hypertension (onset > 20 weeks) + multisystemic signs: - CNS - pulmonary edema - renal dysfunction - liver impairment - thrombocytopenia * Proteinuria is not required for diagnosis

5. Hypertension Elevation of BP ≥140 mmHg systolic and/or ≥90 mmHg diastolic, on two occasions at least 6 hours apart.  Hypertension: SBP > 140 or DBP > 90  Severe hypertension: SBP > 160 or DBP > 110 BP > 4 hours apart

6. Proteinuria means the presence of an excess of   serum   proteins  in the urine . presence of 0.3 g or greater in a 24-hour urine specimen (abnormally high ). Can be secondary to hypertension; proteinuria in someone with high blood pressure is also a first sign of declining kidney function.

7. Classification of hypertension in pregnancy Chronic Hypertension “ Preexisting Hypertension” - present prior to pregnancy/present prior to 20 weeks Gestational Hypertension Develops in late pregnancy, after 20 weeks gestation. Mild hypertension without proteinuria or other signs of preeclampsia(absence of severe features). Resolves by 12 weeks postpartum Preeclampsia Mild Preeclampsia; absence of severe features Severe Preeclampsia; Severe features Preeclampsia superimposed on Chronic Hypertension

8. Severe Preeclampsia Severe features: Symptoms of central nervous system dysfunction = Blurred vision, scotomata , altered mental status, severe headache Symptoms of liver distention = epigastric pain Nausea, vomiting Hepatocellular injury = Serum transaminase concentration at least twice normal Systolic blood pressure ≥ 160 mm Hg or diastolic ≥ 110 mm Hg  Severe Hypertention Thrombocytopenia = <100,000 platelets per cubic milimeter Proteinuria = 5 or more grams in 24 hours Oliguria = <500 mL in 24 hours Severe fetal growth restriction Pulmonary edema or cyanosis Cerebrovascular accident

9. Pathophysiology the pathophysiology of preeclampsia remains largely unknown. However there is strong evidence that a major cause is an abnormal placenta with the involvement of the trophoblast cells found in this tissue . one subset of trophoblast , syncytiotrophoblast , which forms the epithelial layer of the villi, is in direct contact with maternal blood. The clinical syndrome arises from secondary systemic circulatory disturbances due to generalized maternal endothelial dysfunction. There are two broad categories, maternal and placental .

10. Placental Preeclampsia Placental preeclampsia appears to progress in two stages: Arises from poor development of the early placenta and its maternal blood supply, called poor placentation. This results in poor uterine and placental perfusion, yielding the second stage , a state of hypoxia and increased oxidative stress and the release of anti- angiogenic proteins along with inflammatory mediators into the maternal plasma.  A major consequence is generalized   Endothelial dysfunction.

11. poor placentation By 20 th week of pregnancy, the placenta requires increasing access to the maternal blood supply. This is created by extensive remodeling of maternal spiral arteries, which are the end arteries of the uteroplacental circulation. Remodeling depends on one of the subtypes of the trophoblasts . trophoblast invasion is inhibited, the arteries are poorly remodeled, and the capacity of the circulation is too small. This is called poor placentation. Fig. 1 poor placentation; hypoxia as a result.

12. Placental Factors That Might Cause the Maternal Syndrome A hypoxic placenta releases factors into the circulation that cause the clinical features of this condition. These clinical features appear to arise from a generalized inflammatory response, which the causes are not fully understood, But it is believed that t he hypoxic placenta suffers oxidative stress, Such stress is probably the cause of the increased release of trophoblast debris into circulation. This debris is proinflammatory

13. Placental Factors That Might Cause the Maternal Syndrome Several candidate released factors have been suggested; the strongest is the soluble receptor for vascular endothelial growth factor (VEGF)–1 , also known as sFlt1 (soluble fms -like tyrosine kinase 1). It binds vascular endothelial growth factors and deprives the systemic endothelium of essential survival factors. It is therefore anti- angiogenic  causes hypertension and proteinuria, the typical features of preeclampsia. ****higher sFlt1 concentrations in the blood

14. Immunological Considerations In preeclampsia, The abnormal implantation may stem from the maternal  immune system 's response to the placenta, due to lack of established immunological tolerance in pregnancy .

15. Epidemiology Common: affecting around 5% ~ 10% of pregnancies Mortality : 12-13 % of maternal mortality It has the potential to kill mother or baby

16. Pregnancy-Related Mortality United States (1998-2005) Fig 2 being among the leading causes of maternal death. Preeclampsia (12.3%) Other medical conditions (13.2%) Embolism (18%) PE (10%) AFE (8%) Cardiomyopathy (11.5%) CVA (6%) Anesthesia (1%) Unknown (2.1%) Hemorrhage (12.5%) Obstet Gynecol 2010 Cardiovascular disease (12.4%) Infection (11 %)

17. Risk Factors Preeclampsia in a previous pregnancy Age >40 years or <18 years Family history of pregnancy-induced hypertension Chronic hypertension Chronic renal disease Antiphospholipid antibody syndrome or inherited thrombophilia Vascular or connective tissue disease Diabetes mellitus ( pregestational and gestational) Multifetal gestation High body mass index Male partner whose previous partner had preeclampsia Hydrops fetalis Nulliparity

18. Symptoms Symptoms can include  edema  ( swelling ) , nausea, and headaches during pregnancy . Other symptoms were described with Severe preeclampsia

19. complications   Eclampsia ; if preeclampsia left untreated, it may result in   seizures   . HELLP syndrome  is defined as   hemolysis, elevated liver enzymes (liver dysfunction), and thrombocytopenia This condition may occur in 10–20% of patients with severe preeclampsia and eclampsia . the development of hemorrhagic or ischemic   stroke , acute kidney injury , and  acute respiratory distress syndrome  (ARDS). the fetus may suffer nutritional and respiratory insufficiency, asphyxia, or death .

20. Prevention Preeclampsia cannot be prevented because the pathogenesis of preeclampsia is not yet completely understood. Definitive Treatment = Delivery It is one of the most common reasons for induced pre-term delivery . antihypertensive therapy for prevention of stroke. Choice of drug therapy: Acute – IV labetalol, IV hydralazine.. Long-term – Oral methyldopa or labetalol

21. Conclusion The term ‘‘preeclampsia’’ describes a syndrome (a cluster of clinical features) not a disease. The condition is varied in its presentation, features, and outcomes. Further studies are being held for a better understanding of the etiology of preeclampsia. This helps us as doctors to find a better treatment for affected pregnant women .

22. Thank you for your attension

23. References   From the Preeclampsia Project, University of California, San Francisco Supported by National Institutes of Health Grant No. HD 24180. Received for publication January 3, 1989; revised April 19, 1989; accepted May 16, 1989. Reprint requests: James M. Roberts, MD, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, HSE-1462, San Francisco, CA 94143-0550. 6/1/IJ998 Nuffield Department of Obstetrics and Gynaecology , University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. *To whom correspondence should be addressed. E-mail: [email protected] Hypertension in Pregnancy: Report of the American College of Obstetricans and Gynecologists’ Task Force on Hypertension in Pregnancy. ACOG, 2013. District I ACOG Medical Student Education Module 2011   https://en.wikipedia.org/wiki/Proteinuria https://en.wikipedia.org/wiki/hypertension 5. SCIENCE www.sciencemag.org - W O M E N ’ S H E A L T H References and Notes K. Y. Lain, J. M. Roberts, JAMA 287, 3183 (2002). K. Duckitt , D. Harrington, BMJ 330, 565 (2005). C. W. Redman, Placenta 12, 301 (1991). G. J. Burton, E. Jauniaux , J. Soc. Gynecol. Investig . 11, 342 (2004). R. B. Ness, J. M. Roberts, Am. J. Obstet. Gynecol. 175, 1365 (1996). K. Red-Horse et al., J. Clin . Investig . 114, 744 (2004). E. Jauniaux , B. Gulbis , G. J. Burton, Placenta 24 (suppl. A) S86 (2003). S. E. Hiby et al., J. Exp. Med. 200, 957 (2004). P. Parham, Nat. Rev. Immunol . 5, 201 (2005). A. Moffett-King, Nat. Rev. Immunol . 2, 656 (2002). H. Haller et al., J. Reprod . Immunol . 23, 41 (1993). S. A. Karumanchi , Y. Bdolah , Endocrinology 145, 483 (2004). S. E. Maynard et al., J. Clin . Investig . 111, 649 (2003). N. M. Page et al., Nature 405, 797 (2000). . C. W. Redman, I. L. Sargent, Placenta 24 (suppl. A), S21 (2003). B. Huppertz et al., Placenta 24, 181 (2003) M. T. Raijmakers , R. Dechend , L. Poston, Hypertension 44, 374 (2004). N. Sattar , I. A. Greer, BMJ 325, 157 (2002). M. van Dijk et al., Nat. Genet. 37, 514 (2005). D. Haig, in Evolution in Health and Disease, S. C. Stearns, Ed. (Oxford Univ. Press, Oxford, 1999), pp. 77–90.   Redman CW, Sargent IL (2005). "Latest Advances in Understanding Preeclampsia".   Science   308   (5728): 1592–1594.   doi : 10.1126/science.1111726 . PMID   15947178 .

24. 13 ^  Jump up to: a   b   c   d   Davis, J. A.; Gallup, G. G. J. (2006). Platek , Steven M; Shackelford, Todd K, eds. "Female Infidelity and Paternal Uncertainty".   Evolutionary Perspectives on Male Anti-Cuckoldry Tactics: 191–204.   doi : 10.1017/CBO9780511617812.010 . ISBN   9780511617812 .  |chapter= ignored ( help ) ^  Jump up to: a   b   c   Longo, Dan L. (Dan Louis) (2012).   Harrison's principles of internal medicine. New York: McGraw-Hill. pp. 55–61.   ISBN   978-0-07-174889-6 .   Emile R. Mohler (2006).  Advanced Therapy in Hypertension and Vascular Disease . PMPH-USA. pp. 407–408.  ISBN   9781550093186 . Jump up ^   Jun Wu, Cizao Ren , Ralph J. Delfino , Judith Chung, Michelle Wilhelm, & Beate Ritz (2009).   "Association Between Local Traffic-Generated Air Pollution and Pre- eclampsia and Preterm Delivery in the South Coast Air Basin of California"   (PDF). Environmental Health Perspectives . Retrieved 2009-07-05 . Jump up ^   Bramham , K; Parnell, B; Nelson-Piercy, C; Seed, PT; Poston, L; Chappell, LC (Apr 15, 2014).   "Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis." .   BMJ (Clinical research ed.)   348: g2301.   doi : 10.1136/bmj.g2301 . PMC   3988319 .   PMID   24735917 . ^  Jump up to: a   b   c   d   e   f   g   h   i   j   k   l   m   n   Mustafa, Reem ; Ahmed, Sana; Gupta, Anu ; Venuto , Rocco C. (2012). "A Comprehensive Review of Hypertension in Pregnancy".   Journal of Pregnancy2012: 1–19.   doi : 10.1155/2012/105918 .       Fig.1 Epidemiology of preeclampsia and eclampsia in the United States, 1979-1986 Audrey F. Saftlas , PhD, David R. Olson, PhD, Adele L. Franks, MD, Rani K. Atrash , MD, and Robert Pokras , MS Atlanta, Georgia http://www.sciencedirect.com.sci-hub.io/science/article/pii/000293789091176D Fig. 2 Hypertension in Pregnancy: Report of the American College of Obstetricans and Gynecologists’ Task Force on Hypertension in Pregnancy. ACOG, 2013. District I ACOG Medical Student Education Module 2011 taken from Obstet Gynecol 2010   Fig. 3 SCIENCE www.sciencemag.org - W O M E N ’ S H E A L T H   Hypertension in Pregnancy: Report of the American College of Obstetricans and Gynecologists ’ Task Force on Hypertension in Pregnancy. ACOG, 2013. District I ACOG Medical Student Education Module 2011