pathophysiology of preeclampsia March 12, 2008

preeclampsia

preeclampsia is a condition of new-onset hypertension, proteinuria, and edema most often appearing after 20 weeks of pregnancy.

pathogenesis is still poorly understood. existing literature favors preexisting maternal endothelial dysfunction that are triggered by pregnancy. observations that support this include:

• women with preexisting vascular disease are more susceptible
• high plasma fibronectin (involved in wound healing),  Factor VIII antigen, and thrombomodulin (coactivator of anticoagulant Protein C)
• impaired vasodilation (decrease flow-mediation, NO, prostacyclin) and increased vasoconstriction (high endothelins, thromboxanes)

some other possible etiologies include:

• immune rejection of the placenta
• compromised placental perfusion
  • incomplete cytotrophoblastic growth into the myometrial layer

pathophysiology is thought to involve an unregulated release of free thrombin occurs. this can proceed to DIC. a number of factors may cause this:

• an imbalance between circulatory VEGF and anti-VEGF (sFlt-1, sEng) factors shifts against angiogenesis
  
  • this could lead to inadequate vascularization of the placenta
  • could be a primary placental ischemia or secondary to other ischemic factors
• placental hypoperfusion due to abnormal uterine vasculature that is unable to accommodate the normal rise in blood flow to the fetus/placenta
  • this can lead to atherosis, fibrinoid necrosis, thrombosis, sclerotic narrowing of arterioles, and placental infarction
  • could be a primary placental ischemia or secondary to other ischemic factors

one unifying hypothesis:

HELPP

one variant of preeclampsia is HELPP, an abbreviation of:

• Hemolytic anemia
• Elevated Liver enzymes
• Low Platelet count

this condition involves preeclampsia with headache, malaise, edema, and right upper quadrant pain. HELPP often indicates that preeclampsia has triggered hepatic failure.

preeclamptic patients are already prone to spontaneous hemorrhages. the liver is thought to be particularly prone because fibrin split products can deposit in the reticuloendothelial system of the liver. multiple previous subclinical spontaneous hemorrhages within the small hepatic sinusoids and arterioles may go unnoticed symptomatically and leave the liver in a fragile state. fibrin thrombi may be left uncleared in the liver.

occasionally, a trigger (such as DIC) may cause extreme hypoperfusion of the liver, leading to infarction. periportal necrosis can coalesce and form a subcapsular hematoma with rupture of Glisson’s capsule. this results in intraperitoneal hemorrhage.

this progression is rare, but has a high mortality. right upper quadrant pain along with preeclamptic pain is a diagnostic hallmark for HELPP. however, it is best diagnosed with abdominal ultrasound. termination of pregnancy is considered the first step in treatment.

eclampsia

the patient may progress to full eclampsia, which is only defined by convulsions, and is often accompanied by seizures or coma. though preeclampsia often occurs prior to eclampsia, but no preeclamptic signs have to appear for eclamptic convulsion. the underlying pathophysiology is thought to be the same as preeclampsia with additional fulminant DIC triggering vasospasms and the convulsions.

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