Pre-eclampsia remains a leading cause of maternal and perinatal mortality and Pre-eclampsia is generally defined as new hypertension. Guidelines for preeclampsia prevention treatment; magnésio e a internação precoce em casos de pré-eclâmpsia são Fisiopatologia da. La preeclampasia -eclampsia- PE- constituye la máxima complicación de la clínica ocitocina podría participar en la fisiopatología del parto por su actividad.

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It is classically defined by new -onset hypertension and proteinuria after 20 weeks of gestation. In recent years, we have witnessed a substantial advance in the understanding of the pathogenesis of this condition.

In the clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy fissiopatologia identify women at high risk of developing pre-eclampsia, and only two interventions are strongly recommended by the World Health Organization for prevention of pre-eclampsia: Delivery is the only known cure.

Diagnosis; pre-eclampsia; pregnancy; prevention; treatment; vascular endothelial growth factor. Pre-eclampsia PE is a human pregnancy-specific disease defined by the onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman. Worldwide, PE is responsible for approximately 50, maternal deaths annually 1. In this review, the authors describe the pathogenesis, epidemiology, diagnosis, prevention and management of Eclampsiq.

There are many theories, and disagreements, about the final event that precipitates PE.


It seems that several different initial insults converge into a common pathophysiology pathway or two common pathophysiologies, if considering early – and late -onset PE. However, it appears clear that all subtypes of disease are characterized by a disruption of vascular remodeling and a systemic antiangiogenic response.

Ffisiopatologia underlying mechanisms contributing to these changes still remain to be elucidated and might overlap. At the beginning of a successful pregnancy, cytotrophoblast cells of fetal origin migrate through the decidua and part of the myometrium and invade maternal spiral arteries.

This invasion is regulated by several factors, including the cytotrophoblast differentiation from an epithelial to endothelial phenotype pseudovasculogenesis and the immunological interaction between HLA molecules C, E and G and uterine natural killer cells 2.

The maternal spiral arteries become larger vessels of low resistance and are responsible for maintaining blood flow to the developing fetus and placenta.

In pre -eclamptic women, cytotrophoblast cells do not express specific adhesion molecules of the endothelial phenotype and are unable to penetrate the myometrium. The maternal spiral arteries do not turn into larger vascular channels, leading to a decrease fisopatologia uteroplacental blood flow and an increase in uterine vascular resistance 3.

The mechanical constriction of uterine arteries induces placental hypoperfusion and ischaemia. Poor trophoblast invasion of maternal spiral arteries is an early event in disease progression.

However, this phenomenon in not unique to PE, since it also occurs in intrauterine growth restriction in the absence of hypertension, suggesting that it alone is unable to trigger the disease 4. Placentation also requires an extensive angiogenesis to establish an appropriate vascular network to supply fetal needs. The placenta produces a wide variety of pro-angiogenic proteins vascular endothelial growth factor [VEGF] and placental growth factor [PlGF]and angiogenesis inhibitors, such as soluble fms -like tyrosine kinase 1 sFlt -1 and soluble endoglin sEngan inhibitor of capillary formation.

The balance between these pro and antiangiogenic mediators determines normal placental development 4. The reduced uteroplacental perfusion and placental ischaemia causes a release of antiangiogenic factors. Similarly, studies have found an association between the increased placental expression and circulating levels of sEng and the development of PE. Furthermore, Venkatesha et al.

Some in vitro models suggest that hypoxia is not only a consequence of abnormal trophoblast invasion of maternal spiral arteries, but also a cause of it. Burton and Jauniaux 11 showed that pre-eclamptic placentas have multiple markers of oxidative stress, which would not be predicted by hypoxia alone, suggesting a causal role for hypoxia-reperfusion injury in PE pathogenesis.

According to this theory, high-resistance maternal spiral arteries create alternating periods of hypoxia and normal oxygenation as the vessels contract and relax.

An in vitro model showed that reoxygenation of hypoxic tissue results in the production of pro -inflammatory cytokines and sFlt Some articles highlight the role of a maternal immune response in the pathogenesis of PE 12, Several immune-associated conditions for example, autoimmune diseases increase the probability of a woman developing PE. Primiparity and a change of sexual partner are risk factors for PE, suggesting that the response to paternal antigens also plays a role.


Some authors consider that PE arises from an exaggerated maternal vascular inflammatory response with a preponderance of Th1 – type cytotoxic reaction This hypothesis is supported by some studies that show an abundance of soluble markers of neutrophil activation in PE and activation of the complement system. These three cytokines have been used to create animal models that demonstrate the role of inflammation in PE.

La Marca et al. Orshal and Khalil 17 showed that IL-6 administration causes similar increases in blood pressure and proteinuria in pregnant rats, although sFLT-1 levels in these animals were not assessed. Additionally, exposure of an ILknockout mouse to a hypoxic environment during pregnancy resulted in PE symptoms, whereas only fetal growth restriction occurred in wild-type mice exposed to hypoxia Lai et al. Inhibition of IL by passive immunization i.

In rats, the injection of anti-AT1-receptor antibodies during pregnancy induces hypertension, proteinuria and defects in vascular remodelling. The VEGF plays a critical role in the maintenance of normal glomerular endothelial integrity and genetic glomerular VEGF deficiency has been shown to result in endotheliosis with loss of fenestrae.

The VEGF acts as an autocrine factor on the podocyte, reducing apoptosis and promoting podocyte surviva l Circulating sFlt1, originating from the placenta, is able to bind and sequester VEGF, resulting in endothelial cell damage. Nephrin is an essential component of the slit diaphragm, but it also signals within the podocyte, regulating the actin cytoskeleton and, thereby, the podocyte shape.

VEGF interacts with the cytoplasmic domain of nephrin and through this binding reduces podocyte cell size, regulates the foot process structure and glomerular filter integrity Moreover, animals exposed to high levels of sEng had focal endotheliosis without significant proteinuria, whereas those that were exposed to both sEng and sFlt1 developed massive proteinuria and severe endotheliosis.

Since eNOS is of prime importance in regulating vascular tone and also displays angiogenic properties, abrogation of eNOS as a result of elevated sEng levels induces endothelial cell injury and defects in vasodilation The clinical manifestations of PE are non-specific even in severe disease. The diagnosis of PE depends on assessing blood pressure and proteinuria, typically by a 24 -hour urine collection.

The use of the urine protein to creatinine ratio is a more convenient method for the patient, however its use in pregnancy is controversial, and published studies are discordant The most widely accepted diagnostic criteria for PE are presented in Table I. Serum creatinine often remains normal or only slightly increased 1 Renal tubular function is also impaired in PE, with an early dysfunction of uric acid tubular secretion.

The urine sediment is usually benign. The histologic lesion associated with PE is glomerular endotheliosis The glomeruli are enlarged and solidified as a result of narrowed or occluded capillary lumens due to swollen native endothelial cells and, to a lesser extent, mesangial cells. Glomerular cellularity is not significantly increased and the endothelial changes are limited to the glomerular capillaries; arterioles are typically unaffected.

Vascular thrombosis seen on light microscopy is unusual. Others changes, such as proeminent podocytes with protein reabsorption droplets and endocapillary foam cells, are secondary to proteinuria. Immunofluorescence may reveal the presence of fibrin deposits in glomeruli Some authors report low-level glomerular immunoglobulin deposition in severe PE that probably represents non-immunologic insudation Electron microscopy reveals endothelial cells with loss of fenestrations, cytoplasmic swelling owing to fluid and lipid accumulation and capillary occlusion.

Mesangial cells may show similar changes. Severe PE comprises more substantial blood pressure elevations, a greater degree of proteinuria and symptoms of target organ involvement. PE can also be classified into early-onset and late -onset 27 and these subtypes may represent different forms of the disease. Early-onset PE before the 34 th week of gestation is often associated with abnormal uterine and umbilical artery Doppler ultrasound waveforms, fetal growth restriction and adverse maternal and perinatal outcomes.

Late-onset PE after the 34 th week of gestation seems to be strongly associated with maternal features for example, body mass indexnormal or slightly increased uterine artery resistance index and minimal fetal involvement Several factors have been proven to increase the risk of PE, such as: Screening for PE attempts to identify high-risk pregnancies in an effort to modify antenatal care and institute preventive measures in order to reduce maternal and fetal complications.


In the clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy to identify women at a high risk of developing PE. Guidelines from the National Institute for Health and Clinical Excellence NICE 29 recommend routine screening for specific risk factors for PE nulliparity, older age, high body mass index, family history of PE, underlying renal disease or chronic hypertension, multiple pregnancy, more than 10 years between pregnancies, and a personal history of PE.

The detection rates of early-PE and late-PE were Large scale prospective studies are, however, required to evaluate the power of this integrated approach in the clinical practice. The general term prevention can have three different connotations: Primary prevention of PE involves avoiding pregnancy in women at high risk, lifestyle modification or improving nutrient intake in the entire population. Secondary prevention, in the context of PE, implies breaking off the disease process before clinically recognizable disease emerges.

Fisiopatologai prevention relies on the use of treatment to avoid PE complications. A number of trials, reviews, and protocols evaluating strategies for the prevention of PE are available in the scientific literature. Despite the variety of possible prophylactic interventions described, studies have produced disappointing results.

Interventions such as rest, exercise, reduced salt intake, garlic, marine oil, daily supplementation with magnesium, vitamin C, D or E, diuretics, progesterone and nitric oxide showed insufficient evidence to modify the outcomes of PE 33,34, The treatment of PE depends essentially on illness severity, gestational age and fetal wellbeing.

Delivery is the best treatment for PE, but an expectant approach is also recognized in specific situations. Worsening maternal condition such as AKIeclampsia or signs of fetal compromise, are considered indications for prompt delivery regardless of gestational age.

Figure 1 represents a proposed algorithm for PE management Administration of intravenous fluids should be started as soon as possible, not only to restore or maintain renal perfusion, but also to prevent hypovolemia and ensure an adequate uteroplacental perfusion and fetal wellbeing.

However, fluid balance should be monitored closely to avoid overload, since women with severe disease are at risk of pulmonary oedema and significant third-spacing. Some of the antihypertensive drugs commonly used in the general population angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists are contraindicated in pregnancy.

Diuretics are not recommended because of the high risk for volume depletion and are only indicated for treatment of pulmonary oedema. There are some controversies regarding the best drug for the treatment of fisiopatologka during pregnancy.

The most commonly used drugs are methyldopa, s -blockers and dihydropyridine calcium channel blockers such as nifedipine. Methyldopa is regarded as a first-line drug for the maintenance treatment of hypertension in pregnancy, because it is safe, effective and the subject of many studies 28, Intravenous hydralazine and labetalol are recommended for the treatment of hypertensive emergencies.

However, some authors associate the use of hydralazine with a higher risk of persistent fisiopxtologia, hypotension, caesarean delivery, oliguria, abruptio placentae, abnormal fetal heart rate, and low Apgar scores These authors consider that the results are not fisiopatologja enough to guide clinical practice but do not support the use of hydralazine as a first -line drug for the treatment of hypertensive crises in pregnancy.

Other complications of AKI can arise in PE, particularly hyperkalemia, metabolic acidosis and anaemia.

Pre-eclampsia: its pathogenesis and pathophysiolgy

The administration of insulin, glucose and ion exchange resin are recommended for eclapmsia treatment of hyperkalemia. There are no published data regarding the use of resin in pregnant women, but this drug has a local action within the gastrointestinal tract, therefore, there is no reason for a fetal deleterious effect.

This fact has to be taken into account when correcting metabolic acidosis with sodium bicarbonate.