Pre-eclampsia: pathophysiology and clinical implicationsBMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l2381 (Published 15 July 2019) Cite this as: BMJ 2019;366:l2381
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The “cause” of preeclampsia was largely described in some innovative experiments by a Greek gynaecologist and English physiologist working in Oxford and London in the early 1950s (1). Building on some physiological work describing the renal corticomedullary “shunt” in blast victims by Josep Trueta (Professor of Orthopaedics, Oxford), John Sophian inflated balloons in rabbit uteri (2). The kidneys turned white – immediately. When he severed the uterorenal nerves, there was no response; the kidneys remained fully perfused. Sophian argued that there was “increased tension” in the uterus that was transmitted to the kidneys causing a renal corticomedullary “shunt”, and, activation of the renin-angiotensin system. Removal of the “stretch” (at delivery) reversed the syndrome. KJ Franklin, FRS, reported some “experimental findings of obstetrical interest” (3) ! Our group has added “purinergic” P2X3 receptors in arterioles (“early-onset”) and myometrium (“late-onset”) that are induced by denervatory uterine injuries, as the likely initiators (4). Full accounts of preeclampsia (5) as one of the “great” obstetric and gynaecological syndromes caused by injuries to uterine nerves are available on the website (6, www.preeclampsiaexplained.com)
LC Chesley, a contemporary, recorded Sophian’s findings in the first edition of his classic textbook however they had disappeared by the fourth edition (7). Pregnancy hypertension often contributes to fetal hypertension, possibly through passive transfer of vasopressor substances, that provides support for DJ Barker’s hypothesis of the “fetal origins of adult diseases” (8). Adult hypertension is also the consequence of injuries to visceral, vasomotor nerves that release cytokines and growth factors to cause hyperplasia of the tunica media of denervated visceral arterioles (9). Preeclampsia is not a mystery, it is a temporary, though important, part of a lifelong spectrum of largely-preventable, hypertensive disorders that may originate in the uterus and significantly shorten our lives.
1. Sophian GJ. Toxaemias of Pregnancy. Butterworth & Co. Ltd., 1953.
2. Trueta J, Barclay AE (1948) Studies of the Renal Circulation. Published by Charles C. Thomas Springfield.
3. Franklin KJ, Winstone NE (1955) A review of some experimental findings of obstetrical interest. J Obstet Gynaecol Br Emp 62: 29-36.
4. Wu XQ, Cai YY, Xia WT, Quinn MJ (2016) The aetiology of pre-eclampsia, 1945-1953. BJOG 123: 2130.
5. Zhou ZY, XU XX, WU XQ, Quinn MJ. Preeclampsia; the uterine denervation view. Injuries to uterine nerves, the uterorenal “reflex”, and, renal corticomedullary shunt. Clin Obstet Gynecol Reprod Med 2019; 5:1-6
6. Wu XQ, Zhou ZY, XU XX, Quinn MJ. Arteriolar injuries in clinical obstetric and gynecologic syndromes. Clin Obstet Gynecol Reprod Med 2019; 5(1) 1-7.
7. Chesley LC “Hypertensive disorders in pregnancy” New York, New York Appleton-Century Crofts, 1978.
8. Yang WX, Zhang HJ, Quinn MJ. Fetal hypertension. Am J Med 2019 (in press)
9. Li YY, Gu QR, Chen GR, Quinn MJ (2018) Arteriolar injury in hypertension. Am J Med 131: e133-e134.
Competing interests: No competing interests