Proteinuria is the surrogate objective marker that defines the system wide endothelial leak, which characterizes the

preeclampsia syndrome preeclampsia is best described as a pregnancy-specific syndrome that can affect virtually every organ system abnormal laboratory findings in tests of renal, hepatic, and hematological function increase the certainty of preeclampsia. Persistent premonitory symptoms of eclampsia, such as headache and epigastric pain, also increase the certainty. That said, some women may have atypical preeclampsia with all aspects of the syndrome, but without hypertension or proteinuria, or both (Sibai and Stella, 2009).

Headaches or visual disturbances such as scotomata can be premonitory symptoms of eclampsia. Epigastric or right upper quadrant pain frequently accompanies hepatocellular necrosis, ischemia, and edema that stretch Glisson capsule. This characteristic pain is frequently accompanied by elevated serum hepatic transaminase levels. Thrombocytopenia is also characteristic of worsening preeclampsia. It probably is caused by platelet activation and aggregation as well as microangiopathic hemolysis induced by severe vasospasm. Other factors indicative of severe preeclampsia include renal or cardiac involvement as well as obvious fetal-growth restriction, which attest to its duration. Eclampsia The onset of convulsions in a woman with preeclampsia that cannot be attributed to other causes is termed eclampsia. The seizures are generalized and may appear before, during, or after labor. In older reports, up to 10 percent of eclamptic women, especially nulliparas, did not develop seizures until after 48 hours postpartum (Sibai, 2005). Preeclampsia as a Two-Stage Disorder Observations that abnormal interfaces between maternal, paternal, and fetal tissues may cause preeclampsia have led to hypotheses that the syndrome is a two-stage disorder. In this scenario, there is a spectrum to include "maternal and placental preeclampsia" (Ness and Roberts, 1996). According to Redman and colleagues (2009), stage 1 is caused by faulty endovascular trophoblastic remodeling that downstream causes the stage 2 clinical syndrome (Fig. 34-1). There certainly is evidence that some cases of preeclampsia fit this theory. Importantly, stage 2 is susceptible to modification by preexisting maternal conditions that include cardiac or renal disease, diabetes, obesity, or hereditary influences. Such compartmentalization seems artificial, and it seems logical that there likely is a continuous process. Thus, although perhaps helpful to classify the syndrome for research purposes, preeclampsia is clinically more realistically a continuum of worsening disease. Moreover, evidence is accruing that many "isoforms" exist as discussed below. Etiology Writings describing eclampsia have been traced as far back as 2200 BC (Lindheimer and colleagues, 2009). And an imposing number of mechanisms have been proposed to explain its cause. Instead of being simply "one disease," preeclampsia appears to be a culmination of

factors that likely involve a number of maternal, placental, and fetal factors. Those currently considered important include: 1. Placental implantation with abnormal trophoblastic invasion of uterine vessels 2. Immunological maladaptive tolerance between maternal, paternal (placental), and fetal tissues 3. Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy 4. Genetic factors including inherited predisposing genes as well as epigenetic influences A. Normal third-trimester placental implantation shows proliferation of extravillous trophoblasts from an anchoring villus. These trophoblasts invade the decidua and extend into the walls of the spiral arteriole to replace the endothelium and muscular wall. This remodeling creates a dilated low-resistance vessel. B. Placenta in preeclamptic or fetalgrowth restricted pregnancy shows defective implantation. This is characterized by incomplete invasion of the spiral arteriolar wall by extravillous trophoblasts and results in a small-caliber vessel with high resistance.