Preeclampsia Flashcards
Preeclampsia is defined as..
An abnormal condition of pregnancy characterised by onset of acute hypertension after the 24th week of gestation
Signs of preeclampsia
Hypertension
Proteinuria
Oedema
Percentage of all pregnancy affected by preeclampsia
5-8%
Incidence of PE increases with
Gestational age of mother
Multiple gestations
Mild form of PE
Systolic BP >140mmHg and diastolic >90mmHg
Severe form of PE
Systolic BP >160mmHG and diastolic >110mmHg
First stage of defective trophoblast invasion
Occurs early in pregnancy
Uteroplacental circulation remaining in a state of high resistance can be detected by..
Increased resistance of the uterine arteries
Albaiges et al., 2000
Persistant state of underperfusion produces..
Placental hypoxia and oxidative stress
Systemic inflammatory response and endothelial dysfunction leads to..
the onset of clinical symptoms of PE
Ness and Roberts, 1996
Studies show PE disease with strong familial predisposition
Reported that women with first-degree relatives with PE have 5 times more risk of developing
Those with second-degree have double the risk
(Graves 1998, Salonen 2000)
Goddard et al 2007 study
Evaluated 775SNPs in 190 genes in >350 PE mother and offspring pairs
Goddard et al 2007 detected..
6 genes with a significant maternal-foetal genotype interaction related to PE
Goddard et al 2007 6 genes..
IGF1 IL4R GNB3 CSF1 THBS4
Multifactorial polygenic inheritance with..
A genetic component in the development of PE
Trogstad et al., 2004
Uteroplacental variations in renin-angiotensin system
ACVR2
STOX1
Placental angiogenesis heritable variations
PIGF
VEGF
Flt-1
Endogelin
Sovio et al study
Showed that the ratio of sFlt to PIGF can be used as a predictive value of PE
Single association signal close to Fms-like tyrosine kinase 1 on what chromosome
13
Fms-like tyrosine kinase 1 encodes
Soluble Fms-like tyrosine kinase 1
a splice variant of the VEGF
What does soluble Fms-like tyrosine kinase
Exerts antiangiogenic activity by inhibiting signalling of proangiogenic factos
Fms-like tyrosine kinase 1 pathway is central in preeclampsia pathogenesis because..
Excess circulating soluble Fms-like tyrosine kinase 1 in the maternal plasma leads to hallmark features of PE
(Gray et al 2018)
Obesity increases overall risk of preeclampsia by..
2-3 fold
Bodnar et al 2005
Risk of preeclampsia increases with..
obesity
Increasing BMI
Increased risk of PE is present in..
Caucasian and African-American women
Bodnar et al 2007
Features of obesity that provide insight into pathophysiology of PE
Inflammation
Oxidative stress
Inflammation and PE
Adipose tissue generates several inflammatory mediators that can alter endothelial function
Produced more actively in obese individuals
Circulating C-reactive protein are
Inflammatory mediators produced by the liver as well as adipocytes
Circulating C-reactive proteins are elevated in..
Early pregnancy prior to development of PE
Wolf et al 2001 showed
Strong assocation with PE and obese women
circulating C-reactive proteins
Interleukin-6 is a
Potent inflammatory mediator
Interleukin-6 leads to
Vascular damage and is associated with obesity and insulin resistance
Grimble 2002
Tumour necrosis factor alpha (TNF-α) is also produced in adipose tissue BUT
Studies have shown that TNF-α is not higher in obese pregnant women compared to non-obese controls
Founds et al 2008
Autophagy plays an important role in..
Trophoblast function under physiologically low oxygen conditions in normal pregnancy
Autophagy is a process of..
Self-degradation of cellular components in which double-membrane autophagosomes sequester organelles and fucse with lysosomes so that the contents can be digested by lysosomes
Mizushima et al 2010
Autophagy is important in
Extravillous trophoblasts (EVT) invasion and vascular remodelling under physiologically low oxygen conditions
EVTS invade the..
Uterine myometrium up to 1/3 in depth and migrate along the lumina of spiral arterioles replacing the maternal endothelial lining
Autophagy impaired by sENG may be involved in..
(4 things)
Saito and Nakashima 2013
Poor placentation due to impairedEVT invasion and poor vascular remodelling
Systemic inflammation by activating inflammasome and induction of ER stress
Inadequate tolerance by reducing the pool of Treg cells in PE
Cure of PE
Delivering the baby
NHS, 2018
Treatment for severe PE
Hospitalisation and complete bedrest
High protein diet to compensate for loss of protein and increase nutrients for foetus
Magnesium sulphate (4-7.5 mEg/L) helps excretion of fluid to reduce BP and in more severe cases stop convulsions and seizures
Complications
High mortality if undiagnosed
Risk of cerebral haemorrhave
Circulatory collapse
Renal failure
