PRETES 4 Dr. Syah Rini Wisdayanti Sp.OG,M.Kes

TD-S> 140 mm Hg

dan atau

TD-D> 90 mm Hg

<20

Minggu

usia hamil

Kronis/ kehamilan dg

hipertensi Preeklampsia

Superimposed

>20

Minggu

usia hamil

Tanda/ gejala

klinis dan lab

abnormal

Organ tidak

terlibat

Gestasional

hipertensi

Preeklampsia,

Sindroma

Hellp,

Eklampsia

HIPERTENSI DALAM

KEHAMILAN

KLASIFIKASI DAN DIAGNOSIS

HIPERTENSI TERKAIT KEHAMILAN

KRITERIA DIAGNOSIS

DAN KOMPLIKASI

FAKTOR RESIKO

( PNPK preeklamsia)

PATOFISIOLOGI

TEORI MALADAPTIF IMUN

FETUS ( TROFOBLAS )

ANTIGEN

IBU ( MATERNAL ) HLA

G

SEL

NK

Pada kondisi Normal

• Saat trofoblas melakukan invasi ( sebagai antigen janin ) melakukan invasi

ke maternal imun ( bagian ibu ) maka bagian ibu akan mengeluarkan sel NK

yang berfungsi mengontrol invasi trofoblas

• SEL NK berkerja dengan cara

1. Merangsang pelepasan VEGF ( proangigenik faktor )

2. Produksi IL – 8 dan If 10 ( untuk membatasi infasi trofoblas sd tunika

muskularis a. spiralis)

• HLA berfungsi melindungi extravili trofoblas dari penolakan sistem imun

dengan cara modulasi sel naturan killer ibu dimana HLA G membuat sel

trofoblas dikenali sebagai zat yang dapat diterima oleh tubuh ibu ( sisi

maternal )sehingga dapat melakukan invasi

Pada preeklamsi

Terjadi abnormalitas ekspresi HLA G -- sel trofoblas tidak dikenali dengan

baik dihancurkan sel NK gagal Invasi

(william obs 24 pg 97)

KEGAGALAN REMODELING A. SPIRALIS

NORMAL :

Trofoblas menginfasi tunika muskularis

a. spiralis dan jaringan sekitar arteri (

jaringan matrik sekitar arteri menjadi

gembur dan lunak memudahkan

memberikan ruangan a. spiralis untuk

distensi dan dilatasi Dampak :

• Penurunan resistensi vaskuler dan

peningkatan aliran uteroplasenta

Preeklamsia

Terjadi kegagalan invasi sel trofoblas ke

lapisan tunika muskularis a. spiralis dan

jaringan matrik sekitarnya

Dampak :

• Peningkatan resistensi vaskuler dan

penurunan aliran uteroplasenta

RADIKAL BEBAS

Aliran uteroplasenta yang berkurang Plasenta iskemic dan hipoksia

Dilepaskannya oksidan dan radikal

bebas

( HIDROXIL )

HIDROXIL akan merubah as. Lemak

tidak jenuh ( di membran sel )

diubah menjadi PEROKSIDASE

LEMAK

PEROKSIDASE LEMAK akan beredar diseluruh tubuh dalam alirandarah

dan merusak membran endotel seluruh tubuh ( sistemik )

Terjadi disfungsi endotel

(william obs 24 )

DAMPAK KERUSAKAN ENDOTEL

1. Terjadi gangguan fungsi endotel , dimana fx endotel

adalah

1. Mengekspresikan PIGF ( plasenta insulin growth factor)

2. Mengahasilkan NO ( nitrit okside ) suatu dilatator potent

3. Menghasilakan prostasiklin ( vasodilatator kuat )

4. Menghasilkan EDRF ( endotelian derived relaxing factor )

2. Endotel yang rusak akan mengaktifkan faktor pembekuan darah yang

akan menghasilkan fibrin untuk menumpat lapisan endotel yang rusak ,

dampaknya :

• Produksi tromboksan meningkat ( tomboksan adalah suatu

vasokonstriktor kuat )

• Kadar fibronektin meningkat

• Peningkatan endotelin 1 ( suatu vasokonstriktor kuat )

DAMPAK KERUSAKAN ENDOTEL

3.Untuk mengatasi kerusakan tubuh akan mengkompensasi dengan

usaha :

• Meingkatnya pembentukan VRGF ( vaskular endotelial growth factor )pg

112

• Meningkatnya sFLT – 1 ( soluble FMS like tyrosine factor )

Ket :

- VEGF ( vascular endotelial growth factor ): berfungsi menginisiasi vaskulogenesis, angiogenesis dan

meningkatkan lama dan fungsi dari sel trofoblas

- Reseptor terbanyak pada plasenta adalah VEGF reseptor 1 dan VEGF soluble (dikenal pula dengan

sFlt-1 ) banyak terlibat pada kasus preeklamsia dan PJT

- FGF ( fibrobals growth factor ) berkorelasi dengan pertumbuhan janin meningkat pada diabetes (

ditandai dengan plasenta besar dan makrosomia)

- Epidermal growth factor ( EGF ) meningkat pada serum pasien dengan penyakit trofoblas

-

CLINICAL CONFERENCE OBSTETRIC REPORT 12

(preeclamsia etiology and clinical practice , www. Cambridge . Org ))

DAMPAK KERUSAKAN ORGAN

• Eklampsia

• Amaurosis (kebutaan sementara)

• Edema paru

• Ruptur hepar

• Sindrom HELLP

• Hipertensi kronis

• Kardiomiopati hipertensi

• Abrupsio plasenta

SINDROMA HELLP

Merupakan komplikasi Preeklampsia dan Eklampsia

dimana terdapat Hemolisis, Fungsi liver abnormal dan

Trombositopenia.

Dapat terjadi antepartum : 72%, postpartum : 28% (< 48

jam : 80%; >48 jam : 20%)

Wanita dengan Preeklampsia yang dipersulit oleh

sindrom HELLP biasanya memiliki hasil yang lebih

buruk daripada mereka yang tidak memiliki

• 0,5 – 0,9% dari semua kehamilan

• 10 – 20% kasus pada Preeklampsia berat

Karakteristik

• 68% kasus terjadi pada usia kehamilan antara 28 – 36

minggu

• Umumnya pada multipara

• Onsetnya cepat

• Riwayat hipertensi dan proteinuria

• Pada 50% kasus disertai berat badan berlebih dan edema

generalisata

SINDROMA HELLP

ANGKA KEJADIAN

Perubahan patologi Sindroma HELLP: spasme vaskuler, kerusakan endotel vaskuler, konsumsi dan agregasi platelet, deposisi fibrin, iskemi

Kerusakan mekanisme imunitolerans maternal

Aktivasi kompleks dan peningkatan anafilatoksin C3a dan C5a dan kompleks C5b-9 terminal menstimulasi makrofag, leukosit, trombosit

Sintesis substansi aktif vaskuler yang menginduksi konstriksi spastik pembuluh darah, agregasi dan konsumsi platelet akibat kerusakan endotel

Trombositopenia, hemolysis dan peningkatan enzim hati

PATOFISIOLOGI

SINDROMA HELLP

Faktor yang dapat memprediksi HELLP: Membran sinsitiotrofoblas yang memisahkan darah maternal dan fetal mempunyai abnormalitas pada brush

border

Dalam darah wanita simptomatik, konsentrasi mRNA untuk Flt1 (VEGFR-1) dan Eng beberapa kali lipat lebih tinggi pada Sindrom HELLP

Solubel HLA-DR (sHLA-DR) dalam darah ibu meningkat pada trimester kedua dan ketiga menandakan peningkatan reaksi imun maternal terhadap sel-sel janin yang

bersirkulasi yang mengeskpresikan antigen paternal

239 gen down-regulation terlibat pada Sindrom HELLP.

Histopatologi plasenta: thrombosis intravilus dan infark vilus rendah, peningkatan apoptosis dan marker proliferasi tinggi, ekspresi Fas ligand (FasL)

tinggi dan ekspresi vilus trofoblas meningkat

PLASENTAL PATOGENESIS

SINDROMA HELLP

Mikroangipati trombotik

Kerusakan pada endotel vaskular oleh zat anti-angiogenik dan paparan TNF-a yang berinteraksi dengan Von-Willbrand Factor (VWF) pada Sindrom HELLP menyebabkan mikroangiopati

trombotik

Anemia hemolitik mikroangiopati (MAHA)

Terjadi akibat sel darah merah terfragmentasi saat melewati pembuluh darah dengan endotelium dan fibrin yang rusak

Disseminated intravascular coagulation

Mikropartikel fetal menyebabkan aktivitas tissue factor (TF) meningkat. Aktivasi inhibitor mungkin berlebihan menyebabkan fibrin dan agregasi trombosit muncul dalam mikrosirkulasi,

menyebabkan DIC

Mikroangipati trombotik

Kerusakan pada endotel vaskular oleh zat anti-angiogenik dan paparan TNF-a yang berinteraksi dengan Von-Willbrand Factor (VWF) pada Sindrom HELLP menyebabkan mikroangiopati trombotik

MEKANISME PATOGENETIK

PADA SINDROMA HELLP

Disfungsi liver dan ginjal

Derivat FasL plasenta (CD95L) toksik pada hepatosit. FasL memicu produksi TNFa menyebabkan apoptosis dan nekrosis hepatosit. Disfungsi ginjal biasanya disebabkan oleh endoteliosis

glomerulus

Respon inflamasi: DIC fulminan superakut.

Respon inflamasi dengan aktivasi koagulasi dan komplemen akibat partikel sinsitiotrofoblas dan produk plasental yang berinteraksi dengan sel imun maternal dan sel endotel vaskuler

Hipertensi (85%)

Proteinuri (87%)

Nyeri kuadran kanan atas

atau epigastrium (40 –

90%)

Mual dan muntah (29 –

84%)

Sakit kepala (33 – 60%)

Perubahan visual (10 –

20%)

Perdarahan mukosa (10%)

Jaundice (5%)

SINDROMA HELLP

GEJALA KLINIS

SINDROMA HELLP

TANDA

Hemolisis : Dx setidaknya 2 hal berikut

• Anemia hemolysis mikroangiopati (MAHA)

Ditemukannya Schzocytes dan Burr cells pada apusan darah

tepi

• Hemoglobin , Bilirubin (> 1,2 mg/dL), Haptoglobin

Peningkatan Enzim Hepar

• Peningkatan Asparate Aminotransferase (AST) atau Alanine

Minotransferase (ALT) setidaknya 2 kali diatas normanl

• Laktat dehydrogenase setidaknya 2 kali diatas normal

Trombositopenia

• Kadar Trombosit < 100.000/mm3

KRITERIA DIAGNOSIS

Acute fatty liver of

pregnancy

Acute pancreatitis

Antiphospholipid

syndrome

Cholecystitis

Disseminated herpes

simplex

Fulminant viral hepatitis

Hemolytic uremic

syndrome

DIAGNOSIS BANDING

Hemorrhagic or septic

shock

Immune

thrombocytopenic

purpura

Stroke

Systemic lupus

erythematosus

Thrombotic

thrombocytopenic

purpura

CARA KERJA MGSO4

produksi vasodilatasi ringan hingga sedang

Berkerja pada neuromuskular junction dengan cara : me ↓jumlah asetilkolin yang dibebaskan dari celah presinap dan me↓ sensitifitas motor end plate

menurunkan sistem saraf pusat dan perifer, mekanisme aksi magnesium melibatkan depresi sistem saraf pusat yang dimediasi oleh reseptor N-methyl-D-aspartate (NMDA);

me↓ hiperaktivitas uterine meningkatkan aliran darah uterine

NIFEDIPINE SEBAGAI TERAPI LINI PERTAMA

TD sitole > 160 mmHg atau TD diastole > 110

Menetap selama 15 menit

Berikan nifedipin 10 mg oral

Evaluasi TD ulang 20 menit kemudian

masih melampaui ambang batas beri

nifedipin 20 mg oral

Evaluasi TD ulang 20 menit kemudian

masih tinggi -> beri nifediipin 20 mg oral

kedua

Evaluasi TD ulang 20 menit kemudian

masih tinggi -> beri Labetolol 40 mg IV selama 2 menit

Konsultasi fetomaternal , anastesi dan subspesialis perawatan

kritis

Jika ambang batas telah

tercapai ulangi Ukur TD

1jam 1st

• Setiap 10 menit

1 jam 2nd

• Setiap 15 menit

1 jam 3rd

• Setiap 30 menit

4 jam selanjutnya

• Setiap jam

Emergent therapy for

acute – onset, severe

hypertension during

pregnancy and the post

partum periode

The American College of

Obstetricians and Gynecologist

committee opinion No 623, April

2017

• 1. Which of the following drugs are not accepted to be safe for

treating pregnancy hypertension?

• A. Nifedipine

• B. Hydralazine

• C. Magnesium sulphate

• D. Methyl dopa

• E. Diuretics

2. Which of the following is true regarding ABO incompatibility

between mother and the foetus?

• A. May affect the first pregnancy.

• B. Worsens with successive pregnancies

• C. Usually causes significant anaemia of the foetus at birth.

• D. Often requires exchange transfusion.

• E. Is caused by the Rh(D) antigen.

• 3. Which of the following statements concerning

eclampsia is not correct?

• A. Disseminated intravascular coagulation is an associated

hazard

• B. It is the commonest cause of maternal death in the

United Kingdom

• C. It occurs following delivery in about 20−25% of cases

• D. Placental abruption is a recognised association

• E. The maternal mortality rate is highest when it occurs in

the postpartum period

4. Which of the following is correct regarding

hyperemesis gravidarum?

• A. Occurs in 5% of pregnancies

• B. Is associated with missed miscarriage

• C. Is associated with raised maternal alpha-

feto protein levels

• D. Is associated with raised hCG levels

• E. Is commonly due to pyelonephritis

5. Which of the following is not true

concerning pethidine analgesia in labour?

• A. Analgesic effect takes 10−15 minutes to

become apparent

• B. Causes an elevation of the APGAR scores

• C. Causes loss of foetal cardiac beat-to-beat

variability

• D. Is 50% protein bound

• E. Patient-controlled analgesia provides

better pain relief than nurse-controlled

analgesia

6. The bladder is at risk of damage at the

time of which of the following surgery?

• A. Repair of enterocoele

• B. Classical caesarean section

• C. Lower segment caesarean section

• D. Uterine myomectomy

• E. Laparoscopy

7. Which of the following is not true regarding urinary tract infection in pregnancy?

• A. It is associated with preterm labour

• B. It is commonly due to staphylococci

• C. Acute pyelonephritis is associated with intrauterine growth retardation

• D. There is no known, statistically proven association with foetal lie

• E. It may present with vomiting.

8.Which of the following is a recognised

complication of external cephalic

version?

• A. Positive Kleihauer test

• B. Fetal bradycardia

• C. Transient maternal hypertension

• D. Premature rupture of the

membranes

• E. All the above

9.Which of the following is true regarding secondary post-partum haemorrhage?

• A. It is abnormal bleeding that occurs 12 hours postpartum

• B. It may be due to infection

• C. It cannot be controlled by uterine contracting agents

• D. Occurs following 5% of births

• E. Can usually be diagnosed by ultrasound examination of the pelvic organs

10. Which of the following is true regarding the termination of pregnancy?

• A. Is illegal after 20 weeks’ gestation

• B. After 16 weeks is most safely achieved by hysterotomy

• C. Requires the signature of two gynaecologists

• D. Can be achieved by the intra-muscular administration of prostaglandins.

• E. Complications include infertility in about 2% of cases.

11.Which of the following factor does not predispose to ectopic pregnancy?

• A. Endometriosis

• B. Intrauterine contraceptive device

• C. Ovarian fibroids

• D. Pelvic inflammatory disease

• E. Progesterone only contraceptive pill

12. Which of the following is true regarding the

raised alphafetoprotein (AFP) levels at 16 weeks

gestation?

• A. Is an indication for amniocentesis

• B. Is caused by gastroschisis

• C. Accurate dating of pregnancy is not required

for its assessment

• D. May be due to Down syndrome

• E. Should be confirmed by a repeat blood test

13. Which of the following statement regarding induction of

labour is correct?

• A. Can be achieved by amniotomy

• B. Is easiest when the cervix is in a posterior position

• C. Could be achieved by an ergometrine infusion

• D. Is indicated with an uncomplicated dichorionic twin

pregnancy of greater than 36 weeks’ gestation

• E. Cannot be achieved by intravenous prostaglandin

infusion.

14. Which of the following statement is not correct

regarding the first stage of labour?

• A. The latent phase may last for more than

four hours

• B. The active phase should be associated with

cervical dilatation at a rate of at least 1 cm.

per hour

• C. The active phase starts when the cervix is

effaced and 3 cm dilated

• D. Is best charted using a partogram

• E. Epidural anaesthesia has an adverse effect

on the rate of progress in the first stage of labour

15. Which of the following is a recognised complication of a lower segment caesarean

section performed under regional anaesthesia?

• A. Aspiration of gastric contents

• B. Delayed respiratory depression with hydrophilic opioids

• C. Evidence of myocardial ischaemia on the electrocardiograph

• D. Venous air embolism

• E. All the above

16. Which of the following is not true regarding a high foetal head at term in a

primipara?

• A. Can be caused by placenta praevia

• B. Can be caused by a lower-segment uterine fibroid

• C. Is associated with incorrect pregnancy dating

• D. Is an indication for a caesarean section

• E. Has a higher incidence in patients of African origin.

17. Foetal well-being in the third trimester can be usefully assessed by which of the

following parameters?

• A. Serial assessment of symphyseal fundal height

• B. Ultrasound measurement of crown–rump length

• C. Measurement of serum alpha-fetoprotein levels

• D. Measurement of serum oestradiol levels.

• E. None of the above

18. Which of the following is not correct regarding the detection of β-hCG levels during

early pregnancy?

• A. levels which rise less than 50% in 48 hours at 6 weeks may indicate ectopic

pregnancy

• B. levels > 8,000 i.u./l with no scan evidence of an intrauterine pregnancy strongly

suggest ectopic pregnancy

• C. levels < 1,000 i.u./l at 8 weeks suggest ectopic pregnancy or pregnancy failure

• D. levels are above normal in hydatidiform mole

• E. None of the above

19. Which of the following is true concerning sickle

cell disorders in pregnancy?

• A. Sickle cell disorders are most common in

women of Asian origin.

• B. A sickle cell crisis can be precipitated in

conditions of heightened oxygen tension.

• C. Sickle cell disorders are associated with an

increased incidence of hypertension during

pregnancy.

• D. Sickle cell disease results from a variant on

the alpha globin chain.

• E. Partner screening is recommended during

the second trimester

20. Which of the following is not correct

concerning maternal cardiac disease in

pregnancy?

• A. A classification system exists to

determine the mortality risk.

• B. Involvement of the aorta in Marfan’s

syndrome increases the mortality.

• C. The foetus has an increased risk of

congenital heart disease.

• D. Mitral stenosis is an infrequent

complication following rheumatic

heart disease.

• E. Women with primary pulmonary

hypertension should be advised

against pregnancy

21. Which of the following statement is correct regarding the early

pregnancy loss?

• A. Is usually due to hormone deficiency.

• B. Is due to an abnormal karyotype in approximately 5% of cases.

• C. Intrauterine pregnancy cannot co-exist with tubal pregnancy.

• D. An intrauterine pregnancy should be visible on transvaginal

scan if the HCG is > 1,000 i.u./l.

• E. Always needs evacuation

22. Which of the following is not true regarding thyroid

disease in pregnancy?

A. Hyperthyroidism may be associated with IUGR

B. Thiouracil may cause severe liver disease

C. Congenital hypothyroidism is not routinely

screened for in the UK

D. Thyrotoxicosis is associated with increased hepatic

metabolism of “the Pill”

E. raised T_3 and T_4 levels are found in hyperemesis

and molar pregnancy

23. Which of the following is not true concerning

thalassaemia in pregnancy?

• A. Thalassaemia minor may be suspected on a

blood film.

• B. Thalassaemia is particularly

concentrated in a broad band

encompassing the Mediterranean and

Middle East.

• C. The carrier rate in the UK is

approximately 1 in 10,000.

• D. A woman with α-thalassaemia minor can

be reassured that the baby will be healthy.

• E. Presence of thalassaemia trait has no

association with the occurrence of

preeclampsia.

24. Which of the following is not a side effect of alphamethyldopa?

• A. Depression

• B. Nasal congestion

• C. Oedema

• D. Pyrexia

• E. Visual disturbances

25. Which of the following is true regarding hypertension in pregnancy?

• A. It is of little significance unless accompanied by proteinuria

• B. It causes foetal growth restriction in more than half of affected women

• C. It is not associated with an increased incidence of bleeding from placental

praevia

• D. It should be assessed by admission to hospital

• E. It is a contraindication to the use of intramuscular ergometrine.