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DEFINITION

Gestational hypertension Preeclampsia Eclampsia Chronic hypertension Preeclampsia superimposed upon chronic hypertension

Elevated BP first detected after 20 weeks of gestation without proteinuria = transient hypertension
Gestational Hypertension
BP N BP BP N

Proteinuria ()

20th week of pregnancy

Proteinuria 12 weeks () postpartum

Gestational hypertension Preeclampsia-eclampsia Chronic hypertension Preeclampsia superimposed upon chronic hypertension

The syndrome of new onset of hypertension & proteinuria after 20 weeks of gestation in a previously normotensive woman
Preeclampsia - Eclampsia
BP N BP BP N/

Proteinuria ()

20th week of pregnancy

Proteinuria 12 weeks (+) postpartum

Gestational hypertension Preeclampsia-eclampsia Chronic hypertension Preeclampsia superimposed upon chronic hypertension

SBP > 140 mmHg and / or DBP > 90 mmHg that antedates pregnancy, is present before the 20th week of pregnancy, and persists longer than 12 weeks postpartum
Chronic Hypertension
BP BP BP BP

Proteinuria 20th week Proteinuria () () of pregnancy

delivery

12 weeks postpartum

Gestational hypertension Preeclampsia-eclampsia Chronic hypertension Superimposed preeclampsia upon chronic hypertension

Worsening HT w/ new onset proteinuria in a woman w/ chronic HT


Superimposed preeclampsia upon Underlying HT
BP Proteinuria () BP Proteinuria 20th week (+) of pregnancy BP
12 weeks Proteinuria postpartum ( - )/(+)

Functions of the endothelium Regulate vascular permeability Regulate vascular cell growth Mediate inflammatory and immune mechanism Modulate lipid oxidation ( metabolic activity )

Endothelial dysfunction
An imbalance between relaxing and contracting factors between anti -and pro-coagulant mediators or growth-inhibiting and growth promoting factors.

Endothelial cell dysfunction appears to be the central pathomechanism in the pathogenesis of preeclampsia

FIGURE 1. Abnormal placentation in preeclampsia


In normal placental development, invasive cytotrophoblasts of fetal origin invade the maternal spiral arteries, transforming them from small-caliber resistance vessels to high-caliber capacitance vessels capable of providing placental perfusion adequate to sustain the growing fetus. During the process of vascular invasion, the cytotrophoblasts differentiate from an epithelial phenotype to an endothelial phenotype, a process referred to as pseudovasculogenesis or vascular mimicry (left). In preeclampsia, cytotrophoblasts fail to adopt an invasive endothelial phenotype. Instead, invasion of the spiral arteries is shallow, and they remain small caliber, resistance vessels (right). Maynard S,,Annu. Rev. Med. 2008. 59:6178

1. Placental ischemia 2. Very low-density lipoprotein versus toxicity-preventing activity 3. Immune maladaptation 4. Genetic imprinting 5. Deficiency of catechol-Omethyltransferase / 2-methoxyestradiol 6. The role of RAS

Decreased uterine placental blood flow

Placenta ischemia Placental release of factors

Endothelial dysfunction
ET-1 TBX NO PG2 ANG II Sensitivity

Renal pressure natriuresis

Total peripheral resistance

HYPERTENSION
Am J Physiol Heart Circ Physiol 294: H541H550,2008

Lipid peroxides Cytokines

Placental ischemia

Endothelial cell damage

Platelet aggregation

PGI2 NO Endothelin Mitogenic factors (eg, PDGF)

Systemic vasoplasm

Thromboxane A2 Serotonin, PDGF Thrombin

Organ flow

Intravascular coagulation

oxLDL ANG II

TNF-

ICAM 1
LOX-1 AT1R TNFR eNOS iNOS

NAD(P)H oxidase

Big ET-1

O2

NO

NF - B
MMP-2 ET-1 (132 )

ONOO PGI2 synthase Endothelial cell

Role of oxidative stress in the mediation of endothelial cell dysfunction in preeclampsia

Expert Reviews in Molecular Medicine 2006

The place of oxidative stress in the three-stage model of the disease

HUM ONTOGENET 2(1), 2008, 2938

1. Placental ischemia 2. Very low-density lipoprotein versus toxicity-preventing activity 3. Immune maladaptation 4. Genetic imprinting 5. Deficiency of catechol-Omethyltransferase / 2-methoxyestradiol 6. The role of RAS

FFA 15 - 20 weeks before the onset of clinical disease

FFA levels endothelial cell triglyceride accumulation

Sera from preeclampsia women have both a higher ratio of FFA to albumin
lipolitic activity resulting in enhanced endothelial cell uptake of FFA

cytokine-mediated oxidative stress ischemia-reperfusion mechanisms or / and activated leukocytes

1. Placental ischemia 2. Very low-density lipoprotein versus toxicity-preventing activity 3. Immune maladaptation 4. Genetic imprinting 5. Deficiency of catechol-Omethyltransferase / 2-methoxyestradiol 6. The role of RAS

Normal : Interaction between decidual leukocytes and invading cytotrophoblast cells is essential for normal trophoblast invasion and development. Immun maladaptation

Shallow invasion of spiral arteries by endovascular cytotrophoblast cells and endothelial cell dysfunction mediated by an increased decidual release of cytokines, proteolytic enzymes, and free radical species NK cells Th1 predominant inflammatory response profile increased interferon- and TNF- endothelial damage and inflammation systemically

Further investigation !!!!

1. Placental ischemia 2. Very low-density lipoprotein versus toxicity-preventing activity 3. Immune maladaptation 4. Genetic imprinting 5. Deficiency of catechol-Omethyltransferase / 2-methoxyestradiol 6. The role of RAS

Genetic factors
Environment factor
(deficiency in nutritions?)

Endothelial damage

Placental deficiency

Increased demand from embryo?

Clinical signs of preeclampsia

Kanasaki K,Kalluri R, Kidney International,2009

1. Placental ischemia 2. Very low-density lipoprotein versus toxicity-preventing activity 3. Immune maladaptation 4. Genetic imprinting 5. Deficiency of catechol-Omethyltransferase / 2-methoxyestradiol 6. The role of RAS

Figure 2. The putative role of COMT/2-methoxyestradiol (2-ME) in pregnancy. In normal pregnancy, 2-ME may have a role in regulating hypoxia-inducible factor (HIF)1a in diverse ways. In preeclampsia, low COMT/2-ME levels may induce accumulation of HIF-1a, vascular defect, placental hypoxia, and inflammatory responses in the placenta. Such a response may induce placental defects and result in suppression of placental-derived estradiol and further reduction in 2-ME levels. COMT, catechol-Omethyltransferase; CYP450, cytochrome 450.

1. Placental ischemia 2. Very low-density lipoprotein versus toxicity-preventing activity 3. Immune maladaptation 4. Genetic imprinting 5. Deficiency of catechol-Omethyltransferase / 2-methoxyestradiol 6. The role of RAS

Deficient uteroplacental perfusion pressure and blood flow

Progesterone and other mediators


Vascular dysfunction: systemic and multi-organ effects

Reciprocal renal RAS

Uteroplacental RAS

Chronic subpressor angiotensin II

Figure 3. Pathogenesis of preeclampsia Proximate biochemical-molecular event is the activation of uterine RAS. Uterus is the clipped kidney with reduced perfusion pressure, and the two kidneys are the nonclipped kidney with reciprocal suppression of renal RAS, which is manifested in the systemic circulation. RASrenin-angiotensin system.

HYPERTENSION

Deficient vascular remodeling

Proteinuria

Kidney

sFLT1 s EnG

Uteroplacental insufficiency

Activation of decidual RAS

Placental hypoxia

Vascular dysfunction

Elevated subpressor Ang II Vascular maladaptation

Figure 4 : Decidual RAS activation and the placental release of antiangiogenic factors may explain the manifestations of human preeclampsia
Current Opinion in Nephrology and Hypertension 2007, 16:213220

Fetal Compromise

Maternal Outcome Severe Disease Mild Disease

Hypovolemia Vasoconstriction Platelet Aggregation


Balance

presence of underlying disorders: (maternal susceptibility genes) chronic hypertension hyperhomocysteinemia thrombophilic disorders obesity, syndrome X diabetes mellitus

EC Dysfunction

Placental Ischemia
Acute Atherosis

Increased STB Deportation In End-Stage Disease


Cytokine-Mediated Oxidative Stress

EC Adhesion Molecules (neutrophil recruitment)

Shallow Trophoblast Invasion in Spiral Arteries abnormal CTB integrin switching


abnormal decidual CK activity

Immune Maladaptation Genetic Conflict

Risk Factors
Age > 40 years, primiparae

Unadjusted relative risk (95% confidence interval)


1.68 (1.23 2.29) 1.96 (1.34 2.87) 2.90 (1.70 4.93) 2.91 (1.28 6.61) 2.93 (2.04 4.21)

Age > 40 years, multiparae Family history


Nulliparity Multiple pregnancy Preexisting diabetes Prepregnancy body mass index > 35 Previous preeclampsia

3.56 (2.54 4.99)


4.29 (3.52 5.49) 7.19 (5.85 8.83) 9.72 (4.34 21.75)

Antiphospholipis syndrome

SUMMARY THE PATHOMECHANISM OF PREECLAMPSIA

PENCEGAHAN
PEMBATASAN KALORI, CAIRAN, DIIT RENDAH GARAM TIDAK MENCEGAH HIPERTENSI DALAM KEHAMILAN BAHKAN MEMBAHAYAKAN JANIN MANFAAT ASPIRIN, KALSIUM DLL. BELUM TERBUKTI DETEKSI DINI DAN PENANGANAN CEPAT-TEPAT

ALUR TERAPI
HIPERTENSI KARENA KEHAMILAN TANPA PROTEINURIA
HAMIL > 37 MG HAMIL < 37 MG TERMINASI KEHAMILAN PEMANTAUAN TEKANAN DARAH MENINGKAT PREEKLAMPSIA

PENGELOLAAN

HIPERTENSI DALAM KEHAMILAN TANPA PROTEINURIA


JIKA KEHAMILAN < 37 MINGGU
RAWAT JALAN PEMANTAUAN TEKANAN DARAH, PROTEINURIA & KONDISI JANIN TIAP MINGGU BILA KONDISI JANIN MEMBURUK / GANGGUAN PERTUMBUHAN JANIN RAWAT DAN PERTIMBANGKAN TERMINASI KEHAMILAN

JIKA KEHAMILAN > 37 MINGGU


TERMINASI KEHAMILAN

ALUR TERAPI
PREEKLAMPSIA RINGAN

HAMIL > 37 MG

TERMINASI KEHAMILAN PEMANTAUAN


TEKANAN DARAH, PROTEINURIA, REFLEKS, KONDISI JANIN

HAMIL < 37 MG

KENAIKAN PROTEINURIA

GANGGUAN PERTUMBUHAN JANIN TERMINASI KEHAMILAN

KENAIKAN TEKANAN DARAH RAWAT INAP

PREEKLAMPSIA

PENGELOLAAN

PREEKLAMPSIA RINGAN

JIKA KEHAMILAN < 37 MINGGU DAN TIDAK TERJADI PERBAIKAN, LAKUKAN PENILAIAN 2 KALI/MG RAWAT JALAN
PEMANTAUAN TEKANAN DARAH, urin, refleks, kondisi janin. Banyak istirahat. Dieet biasa TIDAK PERLU PENGOBATAN Konseling pasien dan keluarga tntang tanda dan bahaya preeklamsia dan eklamsia

PENGELOLAAN

PREEKLAMPSIA RINGAN
JIKA KEHAMILAN < 37 MINGGU DAN TIDAK MEMUNGKINKAN RAWAT JALAN, RAWAT DI RS
PEMANTAUAN TEKANAN DARAH 2X/HR, PROTEINURIA 1X/HR & KONDISI JANIN BANYAK ISTIRAHAT DIIT BIASA TIDAK PERLU PENGOBATAN TIDAK PERLU DIURETIK, KECUALI TERDAPAT EDEMA PARU, DEKOMPENSASI KORDIS & GAGAL GINJAL AKUT PERTUMBUHAN JANIN TERHAMBAT PERTIMBANGKAN TERMINASI PROTEINURIA KELOLA SEBAGAI PREEKLAMPSIA BERAT TEKANAN DIASTOLIK TURUN SAMPAI NORMAL PASIEN DIPULANGKAN ISTIRAHAT & PERHATIKAN TANDA PREEKLAMPSIA BERAT TEKANAN DIASTOLIK NAIK RAWAT

PENGELOLAAN

PREEKLAMPSIA RINGAN

JIKA KEHAMILAN > 37 MINGGU PERTIMBANGKAN TERMINASI KEHAMILAN


SERVIKS MATANG LAKUKAN INDUKSI OKSITOSIN 5 IU / 500 ml DEKSTROSE 5% 10 TETES/MENIT ATAU PROSTAGLANDIN SERVIKS BELUM MATANG PROSTAGLANDIN / MISOPROSTOL / KATETER FOLEY / BEDAH CAESAR

ALUR TERAPI
PREEKLAMPSIA BERAT DAN EKLAMPSIA
KEJANG
ANTI KONVULSAN

ANTI KONVULSAN ANTI HIPERTENSI PASANG INFUS KESEIMBANGAN CAIRAN PENGAWASAN OBSERVASI TANDA VITAL, REFLEKS, DJJ, EDEMA PARU, UJI PEMBEKUAN DARAH

OLIGURIA SINDROM HELLP KOMA RUJUK

PERSALINAN 12 JAM (EKLAMPSIA) / 24 JAM (PREEKLAMPSIA)

GAWAT JANIN

PARTUS PERVAGINAM

BEDAH CAESAR

PENGELOLAAN

PREEKLAMPSIA BERAT & EKLAMPSIA

PENGELOLAAN KEJANG
ANTI KONVULSAN PERLENGKAPAN PENGELOLAAN KEJANG LINDUNGI DARI TRAUMA BARINGKAN PASIEN UNTUK MENGURANGI RRESIKO ASPIRASI O2 4-6 LITER/MEN

PENGELOLAAN

PREEKLAMPSIA BERAT & EKLAMPSIA

PENGELOLAAN UMUM
JIKA DIASTOLIK > 110 mmHg BERIKAN ANTI HIPERTENSI SAMPAI DIASTOLIK ANTARA 90-100 mmHg PASANG INFUS RINGER LAKTAT UKUR KESEIMBANGAN CAIRAN KATETERISASI URIN JIKA JUMLAH URIN < 300 ML/JAM PANTAU EDEMA PARU PENGAWASAN OBSERVASI TANDA VITAL, REFLEKS & DJJ TIAP 1 JAM LAKUKAN UJI PEMBEKUAN DARAH

PENGELOLAAN

MAGNESIUM SULFAT
DOSIS AWAL MgSO4 40% 4 g , diencerkan , IV SELAMA 5-10 MENIT

DOSIS PEMELIHARAAN
SEBELUM MgSO4 PERIKSA

MgSO4 40% 6 g drip DENGAN 500cc rl 15 tetes per menit


RR 16 KALI/MENIT REFLEKS PATELLA + URIN 30 ML/JAM DALAM 4 JAM TERAKHIR

HENTIKAN PEMBERIAN
SIAPKAN ANTIDOTUM

REFLEKS PATELLA URIN < 30 ML/JAM . FREKUENSI PERNAPASAN <16 X/MNT BANTU PERNAFASAN DENGAN VENTILATOR KALSIUM GLUKONAS 1 g (20 ML 10% IV PERLAHAN-LAHAN SAMPAI ADA PERNAFASAN

PENGELOLAAN

DIASEPAM
DOSIS AWAL DIASEPAM 10 MG IV SELAMA 2 MENIT

DOSIS PEMELIHARAAN
PEMBERIAN MELALUI REKTUM

DIASEPAM 40 MG / 500 ML RINGER LAKTAT TIDAK MELEBIHI 100 MG/JAM


DIASEPAM 20 MG DALAM SEMPRIT 10 ml JIKA MASIH ADA KEJANG DOSIS TAMBAHAN 10 MG/JAM DAPAT DIBERIKAN MELALUI KATETER URIN KE DALAM REKTUM

PENGELOLAAN

ANTI HIPERTENSI
DOSIS AWAL HIDRALAZIN 5 MG IV SELAMA 5 MENIT

DOSIS PEMELIHARAAN JIKA TIDAK TERSEDIA HIDRALAZIN

HIDRALAZIN TIAP JAM ATAU 12.5 MG IM TIAP 2 JAM NIFEDIPIN 5 MG SUBLINGUAL, RESPONS TIDAK MEMBAIK 10 MENIT TAMBAHAN 5 MG SUBLINGUAL LABETOLOL 10 MG IV RESPONS TIDAK MEMBAIK 20 MG IV METILDOPA 3X 250-500 mg/hari

PENGELOLAAN PERSALINAN
Harus diusahakan segera setelah keadaan pasien stabil. PREEKLAMPSIA BERAT PERSALINAN DALAM 24 JAM Periksa serviks Serviks matang, lakukan pemecahan ketuban, induksi persalinan dengan oksitosin Jika pervaginam tdk dpt diharapkan PREEKLAMPSIA PERSALINAN DALAM 24 JAM, EKLAMPSIA PERSALINAN DALAM 12 JAM, lakukan seksio sesarea Gawat janin lakukan seksio sesarea Serviks belum matang, janin hidup , lakukan seksio sesarea

BILA DILAKUKAN BEDAH CAESAR


TIDAK ADA KOAGULOPATI ANESTESIA TERPILIH ANESTESIA UMUM

JIKA TIDAK TERSEDIA ANESTESI UMUM


JANIN MATI BBLR LAKUKAN PERSALINAN PERVAGINAM

JIKA PEMATANGAN SERVIKS BAIK INDUKSI OKSITOSIN 5 IU / 500 ML DEKSTROSE 5% ATAU PROSTAGLANDIN

LAKUKAN RUJUKAN BILA:

OLIGURIA (<400 ML/24 JAM) SINDROM HELLP KOMA BERLANJUT > 24 SETELAH KEJANG

JAM

PERAWATAN POSTPARTUM

ANTI KONVULSAN DITERUSKAN SAMPAI 24 JAM POSTPARTUM / KEJANG TERAKHIR ANTI HIPERTENSI JIKA TEKANAN DIASTOLIK > 110 mmHg PEMANTAUAN JUMLAH URIN

Hipertensi kronik
Jika pasien sblm hamil sudah mndapat obat anti hipertensi dan terkontrol dgn baik, lanjutkan Jika tekanan diastol 110 mmHg atau tekana sistol 160 mmHg atau lbh, berikan antihipertensi Jika terdapat proteinuri, pikirkan superimposed preeklamsia, tangani seperti pre eklamsia

Pantau pertumbuhan dan kondisi janin Tdk ada komplikasi tunggu sampai aterm Gawat janin : terminasi Pertumbuhan janin terhambat : nilai serviks, serviks matang induksi persalinan , belum matang ya matangkan dulu dgn prostaglandin atau kateter foley

Patofisiologi Preeklampsia
Gangguan Plasentasi (remodelling arteri spiralis)

Hipoperfusi Plasenta

Pelepasan Faktor-faktor dari Plasenta


(TNF-, stress oksidatif)

Disfungsi Endotel

Gangguan Pressure Natriuresis Ginjal

Vasokonstriksi Sistemik

Hipertensi