Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts
An English physiologist and Greek obstetrician described two of the three key elements of the pathophysiology of preeclampsia in some remarkable experiments in the early 1950’s (1). Kenneth Franklin and John Sophian noticed blanching of the kidneys with redistribution of the renal blood flow from the cortex to the medulla, and, oliguria after inflating balloons in rabbit uteri . Denervating the kidneys abolished the “uterorenal reflex”. They did not study the sensory mechanism in the uterus.
Recent studies demonstrate similarities between the narrowing of uterine arterioles in preeclampsia, and, similar narrowing in different gynaecological syndromes including chronic pelvic pain with, or without, endometriosis, vulvodynia, irritative bladder and bowel syndromes, adenomyosis etc. (Fig. 1a-b). In both there is irregular hyperplasia of the tunica media and intima. In the gynaecological syndromes this is associated with circumferential layers of injured, abnormal nerve profiles (2, Fig B). These abnormal nerve profiles may express purinergic “stretch” receptors that elicit the “uterorenal reflex” in preeclampsia (3). In the obstetric syndromes that include preeclampsia, there are no circumferential nerves because the arterioles elongate to reach the placental bed during pregnancy whereas the nerves do not (4, Fig A). Injuries to nulliparous uterine nerves result from physical efforts during defaecation and evacuation of the uterus and result in release of cytokines that cause (a) regrowth of abnormal, injured nerves, and, (b) hyperplasia of adjacent tissues including denervated arteriolar walls (2).
The clinical associations of preeclampsia including age, nulliparity, diabetes mellitus, hydatidiform mole, multiple pregnancy, polyhydramnios , pre-existing renal disease, fetal hydrops, etc are largely explained in “early-onset” and “late-onset” preeclampsia by perivascular and myometrial reinnervation respectively (3, 4)). Predicting preeclampsia with some precision may become possible once the prior sources of neural injury and pathophysiology of the preeclamptic syndromes are fully understood.
(2) Atwal G, du Plessis D, Armstrong G, Slade R, Quinn M.
Uterine innervation after hysterectomy for chronic pelvic pain with, and without,
endometriosis.
Am J Obstet Gynecol. 2005; 193(5):1650-5.
(3) Quinn MJ.
Pre-eclampsia - The "uterine reinnervation" view.
Med Hypoth 2014; 83(5):575-9.
(4) Quinn MJ.
Preeclampsia: two placental phenotypes, one etiology.
Am J Obstet Gynecol. 2014; 211(3):313-4.
Rapid Response:
The cause of preeclampsia
An English physiologist and Greek obstetrician described two of the three key elements of the pathophysiology of preeclampsia in some remarkable experiments in the early 1950’s (1). Kenneth Franklin and John Sophian noticed blanching of the kidneys with redistribution of the renal blood flow from the cortex to the medulla, and, oliguria after inflating balloons in rabbit uteri . Denervating the kidneys abolished the “uterorenal reflex”. They did not study the sensory mechanism in the uterus.
Recent studies demonstrate similarities between the narrowing of uterine arterioles in preeclampsia, and, similar narrowing in different gynaecological syndromes including chronic pelvic pain with, or without, endometriosis, vulvodynia, irritative bladder and bowel syndromes, adenomyosis etc. (Fig. 1a-b). In both there is irregular hyperplasia of the tunica media and intima. In the gynaecological syndromes this is associated with circumferential layers of injured, abnormal nerve profiles (2, Fig B). These abnormal nerve profiles may express purinergic “stretch” receptors that elicit the “uterorenal reflex” in preeclampsia (3). In the obstetric syndromes that include preeclampsia, there are no circumferential nerves because the arterioles elongate to reach the placental bed during pregnancy whereas the nerves do not (4, Fig A). Injuries to nulliparous uterine nerves result from physical efforts during defaecation and evacuation of the uterus and result in release of cytokines that cause (a) regrowth of abnormal, injured nerves, and, (b) hyperplasia of adjacent tissues including denervated arteriolar walls (2).
The clinical associations of preeclampsia including age, nulliparity, diabetes mellitus, hydatidiform mole, multiple pregnancy, polyhydramnios , pre-existing renal disease, fetal hydrops, etc are largely explained in “early-onset” and “late-onset” preeclampsia by perivascular and myometrial reinnervation respectively (3, 4)). Predicting preeclampsia with some precision may become possible once the prior sources of neural injury and pathophysiology of the preeclamptic syndromes are fully understood.
References
(1) Sophian GJ
Toxaemias of Pregnancy.
Butterworth & Co. Ltd., 1953.
(2) Atwal G, du Plessis D, Armstrong G, Slade R, Quinn M.
Uterine innervation after hysterectomy for chronic pelvic pain with, and without,
endometriosis.
Am J Obstet Gynecol. 2005; 193(5):1650-5.
(3) Quinn MJ.
Pre-eclampsia - The "uterine reinnervation" view.
Med Hypoth 2014; 83(5):575-9.
(4) Quinn MJ.
Preeclampsia: two placental phenotypes, one etiology.
Am J Obstet Gynecol. 2014; 211(3):313-4.
Competing interests: No competing interests