Gestational hypertension
Preeclampsia-eclampsia
Chronic hypertension
Preeclampsia superimposed
upon chronic hypertension
BP N
Proteinuria
()
Gestational
Hypertension
BP
20th week
of pregnancy
BP N
Proteinuria 12 weeks
()
postpartum
Gestational hypertension
Preeclampsia-eclampsia
Chronic hypertension
Preeclampsia superimposed
upon chronic hypertension
BP N
Proteinuria
()
BP
20th week
of pregnancy
BP N/
Proteinuria 12 weeks
(+)
postpartum
Gestational hypertension
Preeclampsia-eclampsia
Chronic hypertension
Preeclampsia superimposed
upon chronic hypertension
BP
BP
delivery
BP
12 weeks
postpartum
Gestational hypertension
Preeclampsia-eclampsia
Chronic hypertension
Superimposed preeclampsia
upon chronic hypertension
BP
BP
12 weeks Proteinuria
postpartum ( - )/(+)
Endothelial dysfunction
An imbalance between relaxing and
contracting factors between
anti -and pro-coagulant mediators
or growth-inhibiting and growth
promoting factors.
1. Placental ischemia
2. Very low-density lipoprotein
versus toxicity-preventing activity
3. Immune maladaptation
4. Genetic imprinting
5. Deficiency of catechol-Omethyltransferase / 2methoxyestradiol
6. The role of RAS
Decreased
uterine
placental blood
flow
Placenta
ischemia
Placental release of factors
Endothelial dysfunction
ET-1
TBX
NO
Renal
pressure
natriuresi
s
PG2
ANG II Sensitivity
Total
periphera
l
resistanc
e
HYPERTENSI
ON
Lipid peroxides
Cytokines
Placental
ischemia
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
NAD(P)H oxidase
O2
eNOS
NO
iNOS
Big ET-1
NF - B
MMP-2
ONOO
PGI2
synthase
ET-1 (132 )
Endothelial cell
1. Placental ischemia
2. Very low-density lipoprotein
versus toxicity-preventing activity
3. Immune maladaptation
4. Genetic imprinting
5. Deficiency of catechol-Omethyltransferase / 2methoxyestradiol
6. The role of RAS
FFA levels
endothelial cell
triglyceride
accumulation
cytokinemediated
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 / 2methoxyestradiol
6. The role of RAS
1. Placental ischemia
2. Very low-density lipoprotein
versus toxicity-preventing activity
3. Immune maladaptation
4. Genetic imprinting
5. Deficiency of catechol-Omethyltransferase / 2methoxyestradiol
6. The role of RAS
Genetic factors
Environment factor
(deficiency in nutritions?)
Endothelial
damage
Placental
deficiency
Clinical signs of
preeclampsia
Increased
demand from
embryo?
1. Placental ischemia
2. Very low-density lipoprotein
versus toxicity-preventing activity
3. Immune maladaptation
4. Genetic imprinting
5. Deficiency of catechol-Omethyltransferase / 2methoxyestradiol
6. The role of RAS
1. Placental ischemia
2. Very low-density lipoprotein
versus toxicity-preventing activity
3. Immune maladaptation
4. Genetic imprinting
5. Deficiency of catechol-Omethyltransferase / 2methoxyestradiol
6. The role of RAS
Reciprocal
renal RAS
Vascular dysfunction:
systemic and multi-organ
effects
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
Uteroplacental
insufficiency
Vascular
dysfunction
Kidney
Proteinuria
Deficient
vascular
remodeling
Activation
of decidual
RAS
sFLT1
s EnG
Placental hypoxia
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
Maternal Outcome
Fetal Compromise
Severe Disease
Mild Disease
oth
Good end
elium
elium
EC Dysfunction
Placental
Ischemia
Acute
Atherosis
Cytokine-Mediated
Oxidative Stress
Shallow Trophoblast
Invasion in
Spiral Arteries abnormal CTB integrin switching
abnormal decidual CK activity
EC Adhesion
Molecules
(neutrophil
recruitment)
Immune Maladaptation
Genetic Conflict
Risk Factors
Family history
Nulliparity
Multiple pregnancy
Preexisting diabetes
Previous preeclampsia
Antiphospholipis syndrome
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