association for gestational hypertension and for preeclampsia was found (Nilsson, 2004). Ward and Taylor (2015) cite an incident risk for preeclampsia of 20 to 40 percent for daughters of preeclamptic mothers; 11 to 37 percent for sisters of preeclamptic women; and 22 to 47 percent for twins. Ethnoracial factors are important, as evidenced by the high incidence of preeclampsia in African-American women. It may be that Latina women have a lower incidence because of interactions of American Indian and white race genes (Shahabi, 2013).
he hereditary predisposition for preeclampsia likely stems from interactions of literally hundreds of inherited genesboth maternal and paternal-that control myriad enzymatic and metabolic functions throughout every organ system (Triche, 2014). Plasma-derived factors may induce some of these genes in preeclampsia (Mackenzie, 2012). Thus, the clinical manifestation in any given woman with the preeclampsia syndrome will occupy a spectrum. In this regard, phenotypic expression will difer among similar genotypes depending on interactions with environmental components (Yang, 2013).
Hundreds of genes have been studied for their possible association with preeclampsia (Buurma, 2013; Sakowicz, 2016; Ward, 2015). Several that may have a significant association with the syndrome are listed in Table 40-4. However, because of the complex phenotypic expression of preeclampsia, it is doubtful that anyrone candidate gene will be found responsible. Indeed, Majander and associates (2013) have linked preeclampsia predisposition to evenetal genes on chromosome 18.
The concept of vasospasm with preeclampsia has been advanced for a century (Volhard, 1918). Systemic endothelial activation causes vasospasm that elevates resistance to produce subsequent hypertension. Concurrently, systemic endothelial cell injury promotes interstitial leakage, and blood constituents, including platelets and ibrinogen, are deposited subendothelially. Endothelial junctional proteins are also disrupted, and the subendothelial region of resistance arteries undergoes ultrastructural change (Suzuki, 2003; Wang, 2002). The much larger venous circuit is similarly involved.
With diminished blood low because of maldistribution from vasospasm and interstitial leakage, ischemia of the surrounding tissues can lead to necrosis, hemorrhage, and other end-organ disturbances characteristic of the syndrome. One important clinical correlate to this is the markedly attenuated blood volume seen in women with severe preeclampsia (Zeeman, 2009).
Injury to systemic endothelial cells is now a centerpiece of preeclampsia pathogenesis (Davidge, 2015). In this scheme, protein factor(s)-likely placental-are secreted into the maternal circulation and provoke activation and dysfunction of the systemic vascular endothelium. Many facets of the clinical syndrome of preeclampsia are thought to result from these widespread endothelial cell changes.
Intact endothelium has anticoagulant properties. lso, systemic endothelial cells, by releasing nitric oxide, blunt the response of vascular smooth muscle to agonists. Injured or activated endothelial cells may produce less nitric oxide and may secrete substances that promote coagulation and greater sensitivity to vasopressors. Further evidence of endothelial activation includes the characteristic changes in glomerular capillary endothelial morphology, greater capillary permeability, and elevated blood concentrations of substances associated with endothelial activation. Likely, multiple factors in the plasma of preeclamptic women combine to exert these vasoactive efects (Myers, 2007; Walsh, 2009).