Preeclampsia is a serious medical condition characterized by high blood pressure that develops during pregnancy, typically after 20 weeks of gestation. This disorder can affect various organ systems in the mother and also poses risks to the unborn baby. Understanding the underlying biological processes, known as pathophysiology, provides insights into how the condition develops and impacts the body.
Abnormal Placental Development
The initial events leading to preeclampsia originate early in pregnancy with placental development, the organ responsible for nourishing the fetus. In a typical pregnancy, specialized placental cells called trophoblasts deeply invade the maternal uterine wall. These cells remodel the maternal spiral arteries, transforming them from narrow, high-resistance vessels into wide, low-resistance conduits. This remodeling ensures a robust and consistent blood supply to the developing fetus.
In preeclampsia, this remodeling process is often incomplete or shallow. The trophoblasts fail to adequately invade the muscular layers of the spiral arteries, leaving these vessels narrow and less adaptable. This structural abnormality restricts the blood flow to the placenta. This insufficient blood flow leads to placental hypoperfusion (inadequate blood supply) and localized hypoxia (lack of oxygen). This generates stress within the placenta, initiating a cascade of events that contribute to the disease.
Systemic Endothelial Dysfunction
The stressed and oxygen-deprived placenta releases proteins into the mother’s bloodstream. These substances are anti-angiogenic factors, which interfere with the formation and maintenance of healthy blood vessels. Two prominent examples are soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng).
These anti-angiogenic proteins target and neutralize proteins that promote vessel health, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). VEGF and PlGF are crucial for maintaining the integrity and function of the endothelium, which is the delicate inner lining of all blood vessels. When sFlt-1 and sEng bind to and inhibit VEGF and PlGF, the widespread endothelial lining becomes damaged and dysfunctional. This systemic endothelial dysfunction allows fluids and proteins to leak out of the blood vessels, disrupting normal physiological processes across multiple organ systems.
Exaggerated Inflammatory Response
The compromised placental environment and damaged endothelium trigger an inflammatory response. The stressed placenta releases cellular debris and pro-inflammatory substances into the circulation. This activates the maternal immune system, leading to over-activation of immune cells and the release of inflammatory messengers, known as cytokines.
This heightened systemic inflammation is more pronounced than the mild, physiological inflammation typically observed during a healthy pregnancy. The continuous presence of inflammatory cytokines and activated immune cells further exacerbates damage to blood vessel linings. This creates a destructive feedback loop, where endothelial dysfunction promotes inflammation, and inflammation, in turn, intensifies endothelial damage. This cycle contributes to the progression of preeclampsia.
Resulting Organ-Specific Damage
The widespread endothelial dysfunction and exaggerated inflammatory response manifest as damage in maternal organs, leading to the signs and symptoms of preeclampsia. In the kidneys, the filtering units known as glomeruli become damaged and “leaky” due to compromised endothelial cells. This allows large amounts of protein, which should normally be retained in the blood, to spill into the urine, a condition known as proteinuria.
The generalized damage to the endothelium throughout the circulatory system causes blood vessels to constrict and lose their ability to relax properly. This systemic vasoconstriction directly leads to the hallmark sign of preeclampsia: persistently high blood pressure, or hypertension. Reduced blood flow and cellular damage in the liver can cause inflammation and dysfunction of liver cells. This can result in symptoms such as pain in the upper right abdomen and elevated liver enzymes, which are detectable in blood tests.
In severe cases, the brain can be significantly affected by vasospasm, where blood vessels in the brain suddenly narrow, and increased permeability of the endothelial lining. This can lead to fluid leakage and swelling within the brain, contributing to symptoms like severe headaches and visual disturbances. The most severe neurological manifestation is eclampsia, characterized by the onset of seizures in a woman with preeclampsia, directly linked to this cerebral dysfunction.