Sunday, July 18, 2010

CONSULT ROUNDS: Severe Pre eclampsia

Severe Pre eclampsia and eclampsia can occur post partum leading to severe HTN and intracranial damage. Preeclampsia, the syndrome of hypertension and proteinuria that heralds the seizures of eclampsia, remains one of the great mysteries in the field of obstetrics.

It is a diseases of the placenta and the kidney is a major target. Endothelial damage is the hallmark of the disease. Preeclampsia is characterized by a constellation of signs and symptoms, including the new onset of hypertension and proteinuria during the last trimester of pregnancy, usually associated with edema and hyperuricemia.  It occurs only in the presence of the placenta, even when there is no fetus (as in hydatidiform mole) and remits dramatically postpartum. The placenta in preeclampsia is usually abnormal, with evidence of hypoperfusion and ischemia. Severe Pre eclampsia is even more dangerous and it almost leads to termination of pregnancy or delivery. 20% of the cases of both pre eclampsia and eclampsia can be post partum.

Risk Factors :
Multiple gestation
Molar pregnancies
Older maternal age
Family history of preeclampsia (paternal side)
Preexisting hypertension
Chronic renal disease
Diabetes mellitus
Thrombotic vascular disease

Clinical Findings :

The clinical findings of severe preeclampsia are unified by the presence of systemic endothelial dysfunction and microangiopathy, in which the target organ may be the brain (seizures or eclampsia), the liver [the hemolysis, elevated liver function tests, and low platelet count (HELLP) syndrome], or the kidney (glomerular endotheliosis and proteinuria).

Renal dysfunction, proteinuria, and renal pathology
Preeclampsia is associated with a characteristic glomerular lesion, "glomerular capillary endotheliosis” or “bloodless” glomeruli which is a similar lesion seen in Thrombotic Microangiopathy or injury post use of avastin. The pattern of injury is MPGN like, but there are no deposits. Nephrologists have taken an active role in this disease and now we know that the state of this disease is due to decreased VEGF in the body. A factor called placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1 that fall after delivery. Studies now have demonstrated that increased circulating sFlt1 in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PlGF, resulting in endothelial dysfunction in vitro that can be rescued by exogenous VEGF and PlGF. Additionally, VEGF and PlGF cause microvascular relaxation of rat renal arterioles in vitro that is blocked by sFlt1. Finally, administration of sFlt1 to pregnant rats induces hypertension, proteinuria, and glomerular endotheliosis, the classic lesion of preeclampsia. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia. Also, when you have a VEGF knockout mice, you also get a similar renal pathology as you see in pre eclampsia.

Deepti Torri, MD

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