Hipertensi pada Kehamilan

The Working Group classification of hypertensive disorders complicating pregnancy as shown in

Table 34-1 describes four types of hypertensive disease:
1. Gestational hypertensionformerly termed pregnancy-induced hypertension. If
preeclampsia syndrome does not develop and hypertension resolves by 12 weeks
postpartum, it is redesignated as transient hypertension
2. Preeclampsia and eclampsia syndrome
3. Preeclampsia syndrome superimposed on chronic hypertension
4. Chronic hypertension.

Indikator Keparahan Preeklamsia

Insiden dan Faktor Risiko

Preeclampsia often affects young and nulliparous women, whereas older
women are at greater risk for chronic hypertension with superimposed
preeclampsia. Other factors include environmental, socioeconomic, and even
seasonal influences.
Other risk factors associated with preeclampsia include obesity, multifetal
gestation, maternal age older than 35 years, and African-American ethnicity.
Obesity was a major risk factor.
Etiopathogenesis

Any satisfactory theory concerning the etiology and pathogenesis of preeclampsia must account
for the observation that gestational hypertensive disorders are more likely to develop in women
who:
Are exposed to chorionic villi for the first time
Are exposed to a superabundance of chorionic villi, as with twins or hydatidiform mole
Have preexisting renal or cardiovascular disease
Are genetically predisposed to hypertension developing during pregnancy.
Regardless of precipitating etiology, the cascade of events that leads to the
preeclampsia syndrome is characterized by a host of abnormalities that
result in vascular endothelial damage and subsequent vasospasm,
transudation of plasma, and ischemic and thrombotic sequelae.
Preeclampsia as a Two-Stage Disorder

Schematic outlines the theory that the preeclampsia syndrome is a "two-stage disorder." Stage 1
is preclinical and characterized by faulty trophoblastic vascular remodeling of uterine arteries
that causes placental hypoxia. Stage 2 is caused by release of placental factors into the maternal
circulation causing systemic inflammatory response and endothelial activation. (Adapted from
Borzychowski, 2006, and Redman, 2009, and their colleagues.)

Etiologi
preeclampsia appears to be a culmination of factors that likely involve a number of maternal,
placental, and fetal factors. Those currently considered important include:
1. Placental implantation with abnormal trophoblastic invasion of uterine vessels
2. Immunological maladaptive tolerance between maternal, paternal (placental), and fetal
tissues
3. Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy
4. Genetic factors including inherited predisposing genes as well as epigenetic influences.
Abnormal Trophoblastic Invasion

A. Normal third-trimester placental implantation shows proliferation of extravillous trophoblasts

from an anchoring villus. These trophoblasts invade the decidua and extend into the walls of the
spiral arteriole to replace the endothelium and muscular wall. This remodeling creates a dilated
low-resistance vessel. B. Placenta in preeclamptic or fetal-growth restricted pregnancy shows
defective implantation. This is characterized by incomplete invasion of the spiral arteriolar wall
by extravillous trophoblasts and results in a small-caliber vessel with high resistance.

Thus, it is likely that the abnormally narrow spiral arteriolar lumen impairs
placental blood flow. Diminished perfusion and a hypoxic environment
eventually lead to release of placental debris that incites a systemic
inflammatory response
Immunological Factors
Maternal immune tolerance to paternally derived placental and fetal
antigens. Loss of this tolerance, or perhaps its dysregulation, is another
theory cited to account for preeclampsia syndrome.
Redman and colleagues (2009) recently reviewed the possible role of immune maladaptation in
the pathophysiology of preeclampsia. Early in a pregnancy destined to be preeclamptic,
extravillous trophoblast express reduced amounts of immunosuppressive human leukocyte
antigen G (HLA-G). This may contribute to defective placental vascularization in stage 1. Recall
that as discussed in Chapter 3, Immunogenicity of the Trophoblasts, during normal pregnancy, Thelper (Th) lymphocytes are produced so that type 2 activity is increased in relation to type 1
termed type 2 bias (Redman and Sargent, 2008). Th2 cells promote humoral immunity, whereas
Th1 cells stimulate inflammatory cytokine secretion. Beginning in the early second trimester in
women who develop preeclampsia, Th1 action is increased and the Th1/Th2 ratio changes.
Contributors to an enhanced immunologically mediated inflammatory reaction are stimulated by
placental microparticles, as well as by adipocytes (Redman and Sargent, 2008).

Endothelial Cell Activation

In many ways, inflammatory changes are thought to be a continuation of the stage 1 changes
caused by defective placentation discussed above. In response to placental factors released by
ischemic changes or by any other inciting cause, a cascade of events is set in motion (Taylor and
colleagues, 2009). Thus, antiangiogenic and metabolic factors and other inflammatory mediators
are thought to provoke endothelial cell injury.

Faktor Nutrisi (karena kurang konsumsi makan antioksidan)

Faktor Genetik

Pathogenesis

Vasospasme
Vascular constriction causes increased resistance and subsequent hypertension. At the same time,
endothelial cell damage causes interstitial leakage through which blood constituents, including
platelets and fibrinogen, are deposited subendothelially. With diminished blood flow because of
maldistribution, ischemia of the surrounding tissues would lead to necrosis, hemorrhage, and
other end-organ disturbances characteristic of the syndrome.

Endothelial Cell Activation

Intact endothelium has anticoagulant properties, and endothelial cells blunt the response of
vascular smooth muscle to agonists by releasing nitric oxide. Damaged or activated endothelial
cells may produce less nitric oxide and secrete substances that promote coagulation and increase
sensitivity to vasopressors (Gant and co-workers, 1974).

Increased Pressor Responses

pregnant women normally develop refractoriness to infused vasopressors. Women with early
preeclampsia, however, have increased vascular reactivity to infused norepinephrine and
angiotensin II. Moreover, increased sensitivity to angiotensin II clearly precedes the onset of
gestational hypertension. Gant and colleagues (1974) showed that normotensive nulliparas
remained refractory to infused angiotensin II, but those who subsequently became hypertensive
lost this refractoriness several weeks before the onset of hypertension.

Prostaglandin
Penurunan produksi endothelial prostasiklin (PGI2) dan peningkatan sekresi tromboxan A2
sehingga sensitifitas terhadap angiotensin 2 meningkat kemudian terjadi vasokonstriksi. Ini
terjadi pada 22 minggu sebelum terjadinya preeclamsia.

Nitric Oxide
This potent vasodilator is synthesized from L-arginine by endothelial cells. Inhibition of nitric
oxide synthesis increases mean arterial pressure, decreases heart rate, and reverses the
pregnancy-induced refractoriness to vasopressors. In humans, nitric oxide likely is the compound
that maintains the normal low-pressure vasodilated state characteristic of fetoplacental perfusion.

Endothelins
These 21-amino acid peptides are potent vasoconstrictors, and endothelin-1 (ET-1) is the primary
isoform produced by human endothelium . aktivasi endothelial menyebabkan peningkatan
sekresi ET-1 sehingga terjadi vasokontriksi yang lebih parah.