ALL ABOUT PREECLAMPSIA - Preeklampsia - Hipertensi dalam kehamilan

-seizures are only one of several clinical manifestation of “severe” preeclampsia.

-Proposed etiologies include cerebral vasospasm with local ischemia, hypertensive encephalopathy with hyperperfusion, vasogenic edema, and endothelial damage.

-Exactly how magnesium acts as an anticonvulsant in eclampsia is not known. Several mechanisms have been proposed, including selective vasodilatation of the cerebral vasculature,

protection of endothelial cells from damage by free radicals, prevention of calcium ion entry into ischemic cells, and/or as a competitive antagonist to the glutamate Nmethyl- D-aspartate receptor (which is epileptogenic).

-Magnesium also appears to selectively increase cerebral blood flow and oxygen consumption in women with preeclampsia

-The maintenance dose of magnesium sulfate is 2 to 3 g/h administered as a continuous

intravenous infusion. The maintenance phase is given only if a patellar reflex is present

(loss of deep tendon reflexes is the first manifestation of symptomatic hypermagnesemia),

respirations are greater than 12 per minute, and urine output is greater than 100 mL in 4 hours.

Reference:

Errol r. Norwitz, md, phd,* chaur-dong hsu, md, Mph,† and john t. Repke, md†.acute complications Of preeclampsia. Clinical obstetricsandgynecology Volume 45, number 2, 308–329 © 2002, lippincott williams & wilkins, inc.

Patogenesis PREEKLAMPSIA terkait Plasenta

- The pathogenesis of preeclampsia is complex; numerous genetic, immunologic, and environmental factors interact. It has been suggested that preeclampsia is a two-stage disease (1). The first stage is asymptomatic, characterized by abnormal placental development during the first trimester resulting in placental insufficiency and the release of excessive amounts of placental materials into the maternal circulation. This in turn leads to the second, symptomatic stage, wherein the pregnant woman develops characteristic hypertension, renal impairment, and proteinuria and is at risk for the HELLP syndrome (hemolysis, elevated liver function enzymes and low platelets), eclampsia, and other endorgan damage.

Placentation Abnormalities (Stage I)

- Pathologic examination of placentas from preeclamptic pregnancies generally reveals placental

infarcts and sclerotic narrowing of arteries and arterioles, with characteristic diminished endovascular invasion by cytotrophoblasts and inadequate remodeling of the uterine spiral arterioles (2). Although gross pathologic changes are not always seen in the placentas of women with preeclampsia

- It is believed that placental angiogenesis is defective in preeclampsia, as evidenced by failure of the cytotrophoblasts to convert from a more epithelial to endothelial phenotype, based on cell surface marker studies (6,7). Normally, invasive cytotrophoblasts downregulate the expression of adhesion molecules that are characteristic of their epithelial cell origin and adopt a cellsurface adhesion phenotype that is typical of endothelial cells, a process that is referred to as pseudovasculogenesis (7,8). In preeclampsia, cytotrophoblast cells fail to undergo this switching

of cell-surface integrins and adhesion molecules (5). This abnormal cytotrophoblast differentiation is an early defect that may eventually lead to placental ischemia.

- Moreover,mechanical constriction of the uterine arteries produces hypertension, proteinuria, and, in some species, glomerular endotheliosis, supporting an causative role for placental ischemiain the pathogenesis of preeclampsia

The Maternal Syndrome (Stage II)

-The abnormal placentation that results from failure of trophoblast remodeling of uterine spiral arterioles is thought to lead to the release of secreted factors that enter the mother’s circulation, culminating in the clinical signs and symptoms of preeclampsia. All of the clinical manifestations of preeclampsia can be attributed to glomerular endotheliosis, increased vascular

permeability, and a systemic inflammatory response that results in end-organ damage and/or hypoperfusion. These clinical manifestations typically occur after the 20th week of pregnancy.

-mechanism of hypertension and proteinuria in preeclampsia is not well understood.

- Eclampsia, the possibility that severe hypertension might disturb cerebral autoregulation and disrupt the blood–brain barrier. The cerebral edema of eclampsia predominantly involves the posterior, parieto-occipital lobes and is similar to images described in reversible posterior leukoencephalopathy syndrome.

Reference:

Michelle Hladunewich,* S. Ananth Karumanchi,† and Richard Lafayette‡.Pathophysiology of the Clinical Manifestations of Preeclampsia.Clin J Am Soc Nephrol 2: 543-549, 2007. doi: 10.2215/CJN.03761106

Mekanisme kerja MgS04 pada pasien Preeklampsia

1.      Sistem susunan syaraf dan cerebro vaskuler. Mekanisme dan aksi magnesium sulfat mesih belum diketahui dan menjadi pokok pembahasan. Beberapa penulis berpendapat bahwa aksi magnesium sulfat di perifer pada neuromuskular junction dengan minimal atau tidak ada sama sekali pengaruh pada sentral. Tapi sebagian besar penulis berpendapat bahwa aksi utamanya adalah sentral dengan efek minimal blok neuromuskuler. Borges dan Gucer (1978) mengajukan bukti yang meyakinkan bahwa ion magnesium menimbulkan efek pada susunan saraf pusat yang jauh lebih spesifik dari pada depresi umum.

2.      Sistem neuromuskular Magnesium mempunyai pengaruh depresi langsung terhadap otot rangka. Kelebihan magnesium dapat menyebabkan :

- Penurunan pelepasan asetilkolin pada motor end-plate oleh syaraf simpatis.

- Penurunan kepekaan motor end-plate terhadap asetilkolin.

- Penurunan amplitudo potensial motor end-plate.

Pengaruh yang paling berbahaya adalah hambatan pelepasan asetilkolin. Akibat kelebihan magnesium terhadap fungsi neuromuskular dapat diatasi dengan pemberian kalsium, asetilkolin dan fisostigmin. Bila kadar magnesium dalam darah melebihi 4 meq/liter reflek tendon dalam mulai berkurang dan mungkin menghilang dalam kadar 10 meq/liter. Oleh karena itu selama pengobatan magnesium sulfat harus dikontrol refleks fatela

3.      Sistem kardiovaskular. Kadar magnesium 2-5 meq/liter dapat menurunkan tekanan darah. Hal ini terjadi karena pengaruh vasodilatasi pembuluh darah, depresi otot jantung dan hambatan gangguan simpatis. Magnesium sulfat dapat menurunkan tekanan darah pada wanita hamil dengan preeklampsia dan eklampsia, wanita tidak hamil dengan tekanan darah tinggi serta pada anak-anak dengan tekanan darah tinggi akibat penyakit glomerulonefritis akut.

4.      Sistem pernapasan. Magnesium dapat menyebabkan depresi pernapasan bila kadarnya lebih dari 10 meq/liter bahkan dapat menyebabkan henti napas bila kadarnya mencapai 15 meq/liter

5.      Uterus. Hutchinson dkk meneliti 32 penderita yang diberi 4 gram MgSO4 secara intravena dan mendapatkan adanya penurunan kontraksi uterus yang nyata pada 21 penderita , pada 7 penderita terdapat penurunan kontraksi uterus yang sedang dan pada 4 penderita malah di dapatkan penambahan kekuatan kontraksi uterus.

Pada tahun 1959, Hall melakukan penelitian invitro efek magnesium sulfat pada miometrium. Pada penelitian ini megnesium sulfat menyebabkan relaksasi bila konsentrasi mencapai 8-19 mEq/1, penghambatan sempurna dicapai bila konsentrasi magnesium 14-30 mEq/1. pada penelitian invivo, digunakan magnesium sulfat dengan kadar dalam darah 5-8 mEq/1. Toksisitas tampak bila kadar dalam darah mencapai kurang lebih 10 mEq/1. Hall juga mendemontrasikan perpanjangan proses persalinan pada penderita preeklampsia yang diberikan pengobatan dengan magnesium sulfat. Lama proses persalinan secara berlangsung sebanding dengan kadar magnesium sulfat dalam darah.

Kadar magnesium dalam serum untuk tokolitik dipertahankan pada kadar 4-9 mg/dl. Bila digunakan sebagai tokolitik, toksisitas magnesium sulfat sangat jarang meskipun kecepatan pemberiannya kurang lebih 4 g/jam atau pasien penderita penyakit ginjal. Refleks patella akan menghilang bila kadar magnesium plasma 9-13 mg/dl, depresi pernapasan terjadi pada kadar 14 mg/dl. Sebagai antodotum untuk toksisitas magnesium adalah 1 g kalsium glukonas yang dinerikan secara intravena.

More info and reference:

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