Just a presentation covering most of the known etiology and pathophysiology behind PIH

1. Pathophysiology of
Pregnancy Induced Hypertension
Dr. Anusha Rao P
PGY-2 (OBG)

2. • Hypertension is one of the commonest
medical disorders in pregnancy, and a leading
cause of maternal and perinatal mortality.
• Incidence lies between 5-10% and is gradually
increasing.

3. • Normal pregnancy is characterised by:
• Increase in plasma volume(preload) starts from 6th wk,
plateaus at 30th wk. (+50%) so fall in haematocrit.
• Increase in cardiac output, from 5th wk, peaks at 30-34
wks, remains static till term, increases further in labour
and immediately following delivery.
• Decrease in PVR.
• So results in physiological decrease in mean BP during
second trimester but it raises to normal value as
pregnancy advances.

4. • Hypercoagulable state
• 50% Increase in fibrinogen
• 15% fall in platelets
• ESR raised by 4times
• Decreased fibrinolytic activity
• Increase in clotting factors I, VII, IX, X but others
decrease
• All these help to effectively achieve hemostasis
during delivery.

6. EARLY GTN
AETIOLOGY
•BEFORE 30WKS
•SEVERE ADVANCES TO
PREECLAMPSIA
PATHOPHYSIOLOGY
• HIGH INCIDENCE OF POOR
PLACENTATION
• HEMODYNAMIC CHANGES-
VASOCONSTRICTION,
DECREASE CO
PROGNOSIS
POOR PERINATAL
PROGNOSIS
LATE GTN
AETIOLOGY
AFTER 34WKS
BENIGN N RARELY
ADV TO
PREECLAMPSIA
PATHOPHYSIOLOGY
NO E/O PLACENTAL
ISCHAEMIA
HEMODY-INC PLASMA
VOL,CO,NORMAL PVR
PROGNOSIS
GOOD PERINATAL
OUTCOME
6

7. ETIOLOGY
Observation that gestational hypertensive disorders are more
likely to develop in women with the following characteristics:
• Are exposed to chorionic villi for the first time
• Are exposed to a superabundance of chorionic villi, as with
twins or hydatidiform mole
• Have preexisting conditions of endothelial cell activation or
inflammation such as diabetes or renal or cardiovascular
disease
• Are genetically predisposed to hypertension developing
during pregnancy.

8. ETIOLOGY-MECHANISMS
• Placental implantation with abnormal
trophoblastic invasion of uterine vessels
• Immunological maladaptive tolerance
between maternal, paternal (placental), and
fetal tissues
• Maternal maladaptation to cardiovascular or
inflammatory changes of normal pregnancy
• Genetic factors including inherited
predisposing genes and epigenetic influences.

10. • IMMUNOLOGICAL MECHANISMS:
• Loss of maternal immune tolerance to paternally
derived placental and fetal antigens is –dysregulation.
• Risk of pre- eclampsia is appreciably enhanced in
circumstances in which formation of blocking
antibodies to placental antigenic sites might be
impaired.
• Immune maladaptation in preeclampsia in women
destined to be preeclamptic, extravillous trophoblasts
early in pregnancy express reduced amounts of
immunosuppressive non classic HLA G.

12. Incident risk for preeclampsia of
• 20 to 40 percent for daughters of
preeclamptic mothers;
• 11 to 37 percent for sisters of preeclamptic
women;
• and 22 to 47 percent for twins.

13. PATHOGENESIS
• Vasospasm
• Endothelial cell activation
• Increased pressor response
• Prostaglandins
• Nitric oxide
• Endothelins
• Angiogenic and antiangiogenic proteins
(soluble Fms-like Tyrosine kinase 1 and soluble
endoglin)

14. Two stage disorder

15. • 2 Stage process
1. Preclinical (≤20 weeks):
– Inadequate invasion of maternal spiral arterioles by
fetal cytotrophoblasts Insufficient maternal
vascular remodeling and angiogenesis
2. Clinical (normally >20 weeks):
– Oxidatively stressed/hypoxic placenta
 Generalized systemic inflammatory response with
release of anti-angiogenic factors, inflammatory
cytokines, and trophoblast debris
 Maternal syndrome

16. NORMAL PREGNANCY:
• Fetal trophoblast invade walls of spiral arteries
• This disrupts their smooth muscle layer and
converts them into venous-like channels
• Remodelling begins about 10-12 weeks and
continues until around 16-18 weeks
• This allows blood supply to uterus to increase
from 10-15 ml (pre-pregnancy) to 600-800 ml per
minute to meet placental blood flow
requirements at term

17. • Invasion defects in
preeclampsia.
• (A) In a normal placenta, extravillous
cytotrophoblast (ECTB) cells (green)
move into the decidua
(endometrium) and myometrium via
interstitial invasion. Some ECTB
cells enter maternal spiral arteries
and replace the endothelial cells of
the vessel walls, becoming
endovascular ECTB (eECTB) cells,
increasing vessel compliance and
maximizing blood flow into placental
blood spaces.
• (B) In the placenta of a preeclamptic
patient, interstitial invasion is
shallow and limited, with many
ECTB cells in the basal plate
remaining attached to anchoring villi
(AV). Endovascular invasion is
nearly absent, and spiral arterioles
remain ‘stiff’. FV, floating villi.

18. Cardiovascular system
• Cardiac preload affected by diminished
hypervolemia of pregnancy.
• Increased cardiac afterload.
• Endothelial activation with extravasation of
intravascular fluid into extravascular
compartment.
Pulmonary edema may develop despite normal
ventricular function because of an alveolar
endothelial-epithelial leak, compounded by
decreased oncotic pressure from a low serum
albumin concentration

19. • Hemoconcentration is a hallmark of eclampsia
from generalized vasoconstriction that follows
endothelial activation and leakage of plasma
into the interstitial space because of increased
permeability.
• It’s however not as marked in preeclampsia
and gest. HTN.

20. • Hemolysis
May be due to : Microangiopathic hemolysis
Serum lipid alterations
Erythrocyte membrane changes
Manifested by elevated serum lactate dehydrogenase
levels and decreased haptoglobin levels.
Other evidence comes from schizocytosis, spherocytosis,
and reticulocytosis in peripheral blood.

21. KIDNEY
glomerular capillary endotheliosis

22. • GFR and Renal blood flow- decreased
- Inc. S. Uric Acid.
• Decreased excretion of Ca. due to tubular
reabsorption.
• Acute renal failure induced by hypotension
and hypovolemia and associated with obst.
Hemorrhage.

23. LIVER
• First, symptomatic involvement is considered a
sign of severe disease. It typically manifests by
moderate to severe right-upper quadrant or mid
epigastric pain and tenderness.
Infarction may be worsened by hypotension from
obstetrical hemorrhage, and it occasionally causes
hepatic failure.
• Second, asymptomatic elevations of serum
hepatic transaminase levels—AST and ALT—are
also considered markers for severe preeclampsia.

24. • In a third example of liver involvement, hemorrhagic infarction may
extend to form a hepatic hematoma. These in turn may extend to
form a subcapsular hematoma that may rupture.
More than 90 percent had HELLP syndrome, and in 90 percent, the
capsule had ruptured. The maternal mortality rate was 22 percent, and
the perinatal mortality rate was 31 percent.
• Last, acute fatty liver of pregnancy is sometimes confused with
preeclampsia
With its onset in late pregnancy, and often accompanying
hypertension, elevated serum transaminase and creatinine levels, and
thrombocytopenia

25. BRAIN
• Vasogenic edema due to loss of
autoregulatory cerebral vasoconstriction
leading to hyperperfusion.
• Supratentorial herniation is fatal.
• PRES.

26. Neurologic manifestations:
• Headache and scotomatas
• Convulsions
• Confusion- coma
Visual changes:
• Scotomata/ blurred vision/ diplopia
• Occipital blindness - amaurosis
• Blindness from retinal lesions is caused either by
serous retinal detachment or rarely by retinal
infarction, which is termed Purtscher retinopathy

27. HELLP
• It is a syndrome that is characterized by hepatic
endothelial disruption followed by platelet
activation, aggregation and consumption,
ultimately resulting in ischemia and hepatocyte
death.
• Occurs in up to 40% of pregnancies complicated
by severe preeclampsia.
• Variable clinical presentation; 12 to 18% are
normotensive and 13% do not have proteinuria.
• At diagnosis, 30% of women are postpartum, 14%
are term, and 56% are preterm ,among them 49%
are <37wks,7% are <27wks

28. • Periportal or focal parenchymal necrosis in
which hyaline deposits of fibrin like material
↓
Obstruction of hepatic blood flow
↓
Periportal necrosis
Intra hepatic hemorrhage
Subcapsular hematoma
Eventual rupture of Glisson’s capsule

29. • Hemolysis is due to a microangiopathic
haemolytic anaemia (MAHA).
• Presence of fragmented (schizocytes) or
contracted red cells with spicula (Burr cells)
in the peripheral blood smear.
• The diagnosis of haemolysis is supported by
high LDH concentration and the presence of
unconjugated bilirubin, but the demonstration
of low or undetectable haptoglobin
concentration is a more specific indicator.

31. Classifications
TENNESSEE CLASSIFICATION
Based on laboratory criteria
1. Platelet count < 100,000/µL
2. AST ≥ 70 IU/L & LDH ≥ 600 IU/L
3. Hemolysis on peripheral smear
Partial HELLP Full HELLP
Any 2 of 3 criteria All of 3 criteria

32. • MISSISSIPI CLASIFICATION (2006)
CLASS I
– Platelet ≤ 50,000/µL(severe thrombocytopenia)
– AST ≥ 70 IU/L
– LDH ≥ 600 IU/L
– Hemolysis on smear
CLASS II
– Platelet 50,000/µL to100,000/µL (moderate thrombocytopenia)
– AST ≥ 70 IU/L
– LDH ≥ 600 IU/L
– Hemolysis on smear
CLASS III
– Platelet 100,000/µL to150,000/µL (mild thrombocytopenia)
– AST ≥ 40 IU/L
– LDH ≥ 600 IU/L
– Hemolysis on smear

33. • Maternal morbidity assoc. with HELLP
syndrome:
Abruptio placenta 10-15%
DIC 10-15%
Pulmonary edema 6-8%
Acute renal failure 5-6%
ARDS 1-2%
Death 1%

34. THANK YOU