Classification and Pathogenesis of Pre-eclampsia
Classification of Pre-eclampsia:
1. Mild Pre-eclampsia:
Is defined as systolic blood pressure (SBP) of at least 140 mmHg and/or diastolic blood pressure (DBP) of at least 90 mmHg on at least two occasions at least 6 hours apart after the 20th week of gestation in women known to be normotensive before pregnancy and before 20 weeks of gestation plus proteinuria (≥ 300 mg/24 h.). If 24 h. urine collection is not available, then proteinuria is defined as a concentration of at least 30 mg/dL (at least 1+ on dipstick) in at least two random urine samples collected at least 6 hours apart.
➧ Serum urate levels are often elevated in pre-eclampsia. Hyperuricemia is associated with perinatal complications, and although elevated levels have not predicted adverse maternal outcomes, urate is frequently measured in clinical practice.
2. Severe Pre-eclampsia:
Is defined as sustained elevations in SBP to at least 160 mmHg and/or in DBP to at least 110 mmHg for at least 6 hours in association with abnormal proteinuria or if there is hypertension in association with severe proteinuria (≥5 g/24 h.). In addition, pre-eclampsia is considered severe in the presence of multiorgan involvement such as pulmonary edema, oliguria (< 500 mL/24 h.), thrombocytopenia (platelet count < 100000 / mm³), abnormal liver enzymes in association with persistent epigastric or right upper quadrant pain, or persistent severe central nervous system (CNS) symptoms (altered mental status, headaches, blurred vision or blindness).
➧ A severe variant of pre-eclampsia also features hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). This condition occurs in about 1/1000 pregnancies. Predisposing factors are positive family history, hypertension, diabetes, preexisting renal disease, multiple pregnancies, and poor obstetric history. Pre-eclampsia with hepatic dysfunction, without hemolysis, may occur in severe pre-eclampsia.
Pathogenesis of Pre-eclampsia:
➧ The etiology of preeclampsia remains unknown; however, defective remodeling of spiral arteries during trophoblast invasion is a recognized predisposing factor for pre-eclampsia. Abnormal trophoblast differentiation and incomplete invasion by the placenta of uterine blood vessels leads to the formation of a placenta in which uterine spiral arteries fail to undergo the normal thinning out of muscular walls that permits enhanced perfusion of the placenta. Thus, perfusion of the intervillous space is impaired, leading to placental hypoxia.
➧ Pre-eclampsia is characterized by placental hypoxia and/or ischemia, excessive oxidative stress, in association with endothelial dysfunction. The release of soluble factors from the ischemic placenta into maternal plasma plays a central role in the ensuing endothelial dysfunction, the most prominent feature of this disease.
➧ Endothelial dysfunction in pre-eclampsia results from an antiangiogenic state mediated by high circulating levels of soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin in concert with low levels of proangiogenic factors like placental growth factor (PlGF), vascular endothelial growth factor (VEGF). The placenta makes sFlt1 in large amounts, but circulating mononuclear cells are an extra source of sFlt1 in pre-eclampsia.
➧ High-circulating levels of sFlt-1 predate the onset and the severity of pre-eclampsia. Thus sFlt1 acts as a potent inhibitor of VEGF and PIGF by binding these molecules in the circulation and other target tissues, such as the kidneys. Thus excessive sFlt-1 plays a central role in the induction of the pre-eclampsia phenotype as sFLt-1 decreases VEGF binding to its receptor which reduces phosphorylation of endothelial nitric oxide synthase (eNOS) by VEGF leading to reduced eNOS.
Other Pathophysiologic Mechanisms:
Include immunologic intolerance between fetoplacental and maternal tissues, placental and endothelial dysfunction, immune maladaptation to paternal antigens, exaggerated systemic inflammatory response, maladaptation to the cardiovascular or inflammatory changes of pregnancy, dietary deficiencies, and genetic abnormalities.
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