Table 2.

Consecutive sequence of pathophysiologic events associated with preeclampsia.

	Pathophysiologic Process	Figure	Predisposing Factors/Mechanisms	Clinics [references]
Inflammation	Preimplantation fetal signaling	2A	Genetic predisposition	Paternal preeclampsia [8,9]
	Maternal response	2B	Preconceptional paternal antigen immune memory	Primipaternity [6,9]
Local adaptation	Local maternal immune tolerance	2B	Maternal immunologic precondition	Auto-immune disease [13,14]
	Local inflammation	2B	Maternal immunologic precondition	Auto-immune disease [13,14], immune suppression [40]
	Local vascular adaptation	2B	Maternal cardiovascular/endothelial precondition	CV disease [13,14], endoth dysfunction [18]
Systemic adaptation	Systemic maternal immune tolerance	2C	Maternal immunologic precondition	Auto-immune disease [13,14]
	Systemic cardiovascular adaptation	2C	Maternal cardiovascular/endothelial precondition	CV disease [13,14], endoth dysfunction [18]
Early oxidative stress	Local tissue damage & inflammation	4	Maternal (immunologic) precondition	Auto-immune disease [13,14]
	Intercellular mediators, chemokines	4	Genetic/immunologic precondition	Genetic diseases [7.8.10.11], auto-immune diseases [13,14]
IVS hemodynamics	Veno-lymphatic remodelling & Arterial plugging	2C	Venous/ body volume dysfunction	(Subclinical) CV disease [41], body constitution [42,43]
		2C	Maternal immunologic dysfunction	Auto-immune disease [13,14]
	Spiral artery remodelling	1	Maternal arterial/endothelial dysfunction	CV disease [13,14], endoth dysfunction [18]
		1	Arterial response to poor venous adaptation	CV disease [13,14], endoth dysfunction [18]
Systemic Hemodynamics	Body water volume	3	Preconceptional low/high body water volume	Maternal body constitution [83.93], renal disease [13.14]
	Body water expansion upon early CV dysfunction	3	Extravasation/poor intravascular expansion	CV disease [13,14], renal disease [13.14], endoth dysfunction [18]
	Volume induced endoth dysfunction	3	Maternal constitutional/CV/endoth precondition	CV disease [13,14], renal disease [13.14], endoth dysfunction [18]
	Raised venous tone/venous hypertension	4	Maternal precondition	Aut NS [44], endoth dysfunction [18]
	External venous compression	4	Preconceptional raised intra-abdominal pressure	Maternal body constitution [83.93], renal disease [13.14]
		4	Increased gestational rise of intra-abdominal pressure	Large uterine volume [13,14]
Late oxidative stress	Intercellular mediators, chemokines	4	Genetic/immunologic precondition	Genetic [7.8.10.11], maternal disease [13.14], endoth [18], Aut NS [44]
	Systemic inflammation	4	Genetic/immunologic precondition	Genetic [7.8.10.11], maternal disease [13.14], endoth [18], Aut NS [44]
		4	Developing during pregnancy	Genetic [7.8.10.11], maternal disease [13.14], endoth [18], Aut NS [44]

CV: cardiovascular; Endoth: endothelium; Aut NS: autonomic nervous system; IVS: intervillous space.