**2. Pathophysiology**

AFE was first described in the 1920s by J.R. Meyer. It was later recognized as a syndrome in 1941 when Steiner and Lushbaugh reported autopsy findings of 32 women who died suddenly during childbirth. The common histopathological finding among these women was the presence of amniotic fluid debris in the pulmonary vasculature [1]. Therefore, the historical hypothesis was based on an obstruction of the pulmonary arteries from amniotic fluid or fetal debris [1, 3]. Medical advancements in the 1980s allowed for more frequent use of the pulmonary artery catheter to obtain arterial histologic specimens from living patients [1]. There were several reports of pathologic findings that were previously thought to be diagnostic of AFE found in pregnant women that did not have AFE. These findings called into question previous cases diagnosed as AFE that were based solely on pathologic findings.

The second and more commonly accepted theory is that AFE results from a complex sequence of reactions involving an abnormal activation of proinflammatory mediators in the host leading to an immunologic response [1–7]. This response is similar to the systemic inflammatory response syndrome (SIRS). Amniotic fluid contains several procoagulant factors including platelet-activating factor, leukotrienes, bradykinin, cytokines, thromboxane, and arachidonic acid, which aids in the understanding of why disseminated intravascular coagulation (DIC) is observed in 80% or more of women diagnosed with AFE [1, 7, 8]. In conjunction with these responses, a profound hemodynamic change leads to the maternal collapse and death in patients with AFE. Thus, during the first minutes, a sudden increase in pulmonary vascular resistance as a result of an inflammatory/anaphylactoid vasoconstriction leads to a right ventricular dysfunction with dilation of the right ventricular chambers, with a left shift of the interventricular septum and a decrease of the left ventricular filling pressures, with hypotension and cardiovascular collapse [9]. This severe pulmonary vasoconstriction produces an oxygen shunt, with ventilation-perfusion mismatching and severe hypoxia. Finally, left ventricular failure may be present as a consequence of myocardial injury secondary to some inflammatory mediators or myocardial ischemia [10].

Complement activation is thought by some to play a role in the pathophysiology of AFE. Virtually all patients diagnosed with AFE develop some degree of acute respiratory distress syndrome (ARDS). Various case series evaluating serum complement levels in patients with AFE have noted significantly decreased levels of C3 and C4 compared to a control group of normal laboring patients who all had complement levels within the normal range [7]. Decreased levels of C3 are thought to be consistent with complement activation.
