hypertension in pregnancy,ethiopathogenesis

Obstetrics and gynaecology

1. ETIOPATHOGENESIS OF
HYPERTENSIVE DISORDERS
COMPLICATING
PREGNANCY
M.ELAKIYA
2
nd
UNIT

2. PREDISPOSING FACTORS

3. - family history of pre-eclampia and
hypertension
- race and ethinicity(common in asians)
- genetic predisposition
-Teenage pregnancy and age more than
40 yrs
-nulliparity (3-10% increased risk)
-new paternity
AGE,PARITY and PARTNER FACTORS

4. - Multiple pregnancy
- molar pregnancy
-fetal chromosomal anomalies(trisomy21)

- Diabetes mellitus
- chronic hypertension
- renal and cardiovascular diseases
- hyperhomocyteinemia

PREGNANCY FACTORS
UNDERLYING MEDICAL CONDITIONS

5. - autoimmune diseases
- Metabolic syndrome
- Antiphosholipid antiboby syndrome
:

- Psychological stress
- obesity
- environmental factors
OTHERS

6. Pre-eclampsia is considered as a two stage
disorder

7. •The Two Stage Model of preeclampsia
proposes that a poorly perfused placenta
(Stage 1) produces factors leading to the
clinical manifestations of preeclampsia
(Stage2).
•Stage 1 is not sufficient to cause the disease
but interacts with maternal constitutional
factors to result in Stage 2.

8. •The abnormalities in the development of
placental vessels in the first trimester may
result in relative placental
hypoperfusion,hypoxia and ischemia.
•The oxidatively stressed placenta releases anti-
angiogenic factors like PG’s and cytokines and
hypoxic placenta decreases the production of
proangiogenic factors.
•These changes alter the maternal systemic
endothelial function and leads to hypertension
and other systemic manifestations.

9. ETIOLOGICAL FACTORS
•Placental implantation
with abnormal
trophoblast invasion
•Immunological factors
•Endothelial cell
activation
•Genetic factors
•Imbalance between
agonist and antagonistic
factors

10. ABNORMAL TROPHOBLASTIC
INVASION
Normal implantation is characterised by extensive
remodelling of spiral arterioles within the desidua
basalis.
In the first trimester(10 – 12 weeks) trophoblasts
invades upto the desidual segments and in 16 to 18
weeks there is another wave of trophoblasts invading
upto the myometrium to invade the maternal spiral
arteries.
 In pre-eclampsia,there is failure of second wave of
trophoblast migration and there is reduction in blood
supply to fetoplacental unit

12. •In pre-eclampsia,there is failure of second
wave of trophoblast migration and there is
reduction in blood supply to fetoplacental unit

14. IMMUNOLOGICAL FACTORS
Immunological maladaptative tolerance between
maternal,paternal(placental),fetal tissues in pre-
eclampsia
•Normally there is maternal immune tolerance to
paternally derived placental and fetal antigens.
•Loss of this tolerance, or perhaps its dysregulation,
account for preeclampsia syndrome.
•Dysregulation include “immunization” from a
previous pregnancy, some inherited human
leukocyte antigen (HLA) and natural killer (NK)-cell
receptor haplotypes,and possibly shared
susceptibility genes with diabetes and hypertension

15. ENDOTHELIAL CELL ACTIVATION

16. Microvascular
coagulation
thrombocytopenia
Increased
capillary
permiability
proteinuriaedema
Vasospasm

17. GENETIC FACTORS
•Pre eclampsia is a multifactorial and polygenic
disorder.
•According to Ward and Lindheimer(2009)
-20-40 % for daughters of pre eclampsia
mothers
-11-37 % for sisters of pre eclampsia women
-22-47 % in twins

19. IMBALANCE OF AGONIST AND
ANTAGONISTIC FACTORS

 Vasoconstrictors and vasodilators
Proangiogenic and anti-angiogenic factors

20. Normally, placenta liberates angiotensinase
which degrade angiotensin II.
• Vascular synthesis of prostaglandin I2 and NO
neutralizes the vasoconstrictive effect of
angiotensin II.
• Increased level of VEGF restores the
uteroplacental blood flow to normal.
• All these maintain blood pressure in normal
state during pregnancy.
VASODILATOR AND VASOCONSTRICTORS

21. IN PRE-ECLAMPSIA
• PGI2 production
•TXA2
•PGI2 : TXA2
• Sensitivity to ATII
•Nitric oxide Deficiency
VASOCONSTRICTION

22. PRO ANGIOGENIC AND ANTI
ANGIOGENIC FACTORS
•A variety of proangiogenic(VEGF,PlGF) and
antiangiogenic(sFlt-1) are elaborated by the
developing placenta and their balance is
important for normal placental development.
•sFlt-1 antagonises the proangiogenic activity by
binding to VEGF AND PlGF
•Soluble endoglin(sEng) is a coreceptor for TGF
produced by the placenta is an anti angiogenic
factor and is another important mediator in pre
eclampsia

24. PATHOGENESIS
•Basic pathology involved is
Vasospasm
Endothelial cell dysfunction
Vasospasm is a result of imbalance between
vasodilator and vasoconstrictors
Endothelial dysfunction is due to oxidative stress
and inflammatory mediators .Both are in a vicious
cycle.

25. •VASOSPASM :
-Vascular constriction increase in resistance
and causes increased blood pressure.
•ENDOTHELIAL CELL ACTIVATION :
- due to release of placental factors and circulating
endothelial cells(CEC) leads to endothelial
dysfunction
•INCREASED PRESSOR RESPONSES - Sensitivity to
AG II
•NITRIC OXIDE – vasodilator ,it is produced from L-
arginine by endothelial cells
In pre-eclampsia- synthesis
•ENDOTHELINS – vasoconstrictor,produced from
human endothelium;levels are high in pre-eclampia

27. PATHOLOGICAL EFFECTS

28. CARDIOVASCULAR CHANGES
 peripheral resistance due to hypertension
leading to increased afterload and decreased
cardiac output
 cardiac preload due to reduced hypervolemia
of pregnancy.
Endothelial activation and extravasation of
intravascular fluid into extracellular space
leading to pulmonary edema.

29. HEMODYNAMIC CHANGES
•Vasoconstriction and
increased endothelial
permeability
•Decrease in blood volume
compared to normal
pregnancy
•Third spacing of fluid due to
increased capillary
permeability

30. PLATELETS
•Endothelial activation Platelet activation &
aggregation platelet deposition at sites of
endothelial damage platelet exhaustion

+
MICROANGIOPATHIC HEMOLYSIS AND
HEPATOCELLULAR NECROSIS

THROMBOCYTOPENIA
HELLP SYNDROME

31. COAGULATION DYSFUNCTION
•Increased factor VIII consumption.
•Increased levels of fibrinopeptides A and B
and fibrin degradation products
•Decreased level of regulatory protein –
Antithrombin III,protein C and S
•Coagulopathy due to abnormal endothelial
expression of procoagulants.
•Increased risk of DIC

32. LIVER CHANGES
Periportal
hemorrhagic
necrosis
Subcapsular
hematoma
Stretching /rupture
of glisson ‘s capsule
Epigastric pain
Raised serum
transaminases
HELLP
syndrome

33. RENAL CHANGES

34. • Glomerular capillary endotheliosis blocking
the filtration barrier.
• Renal tubular lesions are common in patients with
eclampia. It may also lead to acute renal failure.

35. CEREBRAL CHANGES
Forced vasodilatation leads to vasogenic edema
cortical and subcortical petechial hemorrhages
Posterior reversible encephalopathy syndrome and
seizures

36. •ENDOCRINE CHANGES



• VISUAL CHANGES
- SCOTOMA,
- BLURRED VISION,
- DIPLOPIA

- RETINOPATHY
- BLINDNESS

37. PLACENTAL CHANGES
•In pre eclampsia, the placental vessels may be
occluded by fibrinoid material and exhibits
atherosis.
•There is increased synctial knots,villous
necrosis.
•This leads to microinfarcts in placenta and is
responsible for abruption due to desidual
necrosis, separation and hemorrhage

39. CLINICAL TYPES
PRE- ECLAMPSIA
MILD SEVERE

40. CLINICAL FEATURES

42. REFERENCES
•Mudaliar and Menon’s Clinical obstetrics(12
th

edition)
•Williams obstetrics(24
th
edition)