HYPERTENSIVE

DISORDERS OF
PREGNANCY
Prof (Dr.) Amit Kyal
 • Hypertension: 5-10% of all pregnancies

• Pre-Eclampsia: 4-5% of all pregnancies

BACKGROU
ND • Maternal mortality: 7-16%

• More than half of maternal deaths due to

these are preventable
 • Pre-Eclampsia – Eclampsia syndrome

• Chronic hypertension
Terminologi
es (ACOG • Pre-Eclampsia superimposed on chronic
2013) hypertension

• Gestational Hypertension
 • SBP ≥ 140 or DBP ≥ 90 mm of Hg

• Increase in SBP by 30 mm of Hg and/or DBP

by 15 mm of Hg in mid pregnancy  No
Diagnosis longer used
of
Hypertensi • Delta Hypertension:
○ A sudden rise in MAP but still in a normal
on range
○ Some will develop preeclampsia or eclamptic
seizures / HELLP syndrome while still
normotensive
 ● BP ≥ 140/90 mm Hg for the first time in
pregnancy after 20 weeks of gestation in a
previously normotensive women & not
associated with proteinuria
Gestation ● BP returns to normal by 12 weeks
al postpartum
hypertensi ● Half of these women subsequently develop
on (GH) preeclampsia syndrome

● 10% eclamptic seizures develop before

overt proteinuria can be detected.
 • Pregnancy specific Syndrome that can affect virtually every
organ system
• Diagnosis (ACOG,2013)
Pre-Ecl: Hypertension PLUS

Pre- • Proteinuria: ≥ 300 mg in 24hrs / Urine Protein:

Creatinine ≥ 0.3 / Dipstick ≥ 1+ persistent
Eclampsia OR
• Thombocytopenia: Platelet <106 / µL
Syndrome • Renal Insufficiency: Serum creatinine>1.1 mg/dL or
double the baseline
(Pre-Ecl) • Liver Involvement: Serum transaminases twice
normal
• Cerebral Symptoms: Headache, Visual disturbances,
Convulsion
• Pulmonary Edema
 1. Early onset PE(with delivery at <34 +0
weeks of gestation)

Classificati 2. Preterm PE(with delivery at <37+0 weeks of

gestation)
on of
Preeclamp 3. Late-onset E(with delivery at ≥ 34+0 weeks
sia of gestation)

4. Term PE (with delivery at ≥ 37 +0

weeks of gestation)
 Abnormality Nonsevere Severe

DBP <110 >=110

SBP <160 >=160

Proteinuria None to +ve None to +ve

Headache Absent Present

Indicators Visual Disturbances Absent Present

of Upper Abdominal Pain

Oliguria
Absent

Absent
Present

Present

Severity Convulsion (Eclampsia) Absent Present

(C10I3F1)
Pulmonary Edema Absent Present

Gestational Age Late Early

Ser. Creatinine Normal Elevated

Thrombocytopenia Absent Present

Serum Transaminase Minimal Marked

FGR Absent Present

 • Chronic underlying hypertension : Women
with documented blood pressures >140/90
Preeclamps mm Hg before pregnancy or before 20 weeks
ia gestation
superimpo
• Superimposed preeclampsia: If new-onset or
sed on worsening baseline hypertension is
Chronic accompanied by new-onset proteinuria or
other diagnostic criterias of preeclampsia
Hypertensi
on • More severe and more often accompanied
by FGR
 Nulliparous(3-10%, compared to 1.4-4% in multi)

Prior preeclampsia

Chronic hypertensives, CVD, CKD

Risk
Diabetes, Obesity
factors of
preeclamp Multifetal gestation

sia BMI > 30

APLA Syndrome, SLE

ART, Prior abruption, Hyperhomocysteinemia, HIV

seropositivity
 • Exact etiology still unknown
• What we know: More in women who
 Are exposed to chorionic villi for first time
Are exposed to superabundance of chorionic
Etiopathogen villi (Multiple pregnancy, H. Mole)
Have pre-existing conditions associated with
esis endothelial cell activation or inflammation (e.g
Diabetes, Obesity, Cardiovascular or Renal
disease & Immunological disorders)
Genetically predisposed to hypertension
 Systemic Vascular endothelial damage
↓
Cascade
Resultant vasospasm
of ↓
Preeclamp Transudation of Plasma
sia ↓
Ischemic and Thrombotic sequelae
 • Stage I(Placental syndrome) : Faulty
endovascular trophoblastic remodeling
Phenotypic
Expression • Stage II(Maternal syndrome) : Clinical
of Syndrome
Preeclamp
sia Stage II can be modified by preexisting
maternal conditions that also manifest
-Two Stage endothelial cell activation or inflammation
Disorder
(Redman`s Theory)
 Placental implantation with abnormal
trophoblastic invasion of uterine vessels

Immunological maladaptive tolerance

between maternal, paternal (placental) &
fetal tissues
Etiology
Maternal maladaptation to cardiovascular or
inflammatory changes of normal pregnancy

Genetic factors including inherited

predisposing genes & epigenetic influences
 • Normally there is invasion of the endovascular
trophoblasts into the walls of the the spiral
Abnormal arterioles
• In 10–12 weeks, invasion up to decidual segments
trophobla and in 16–18 weeks another wave of invasion up
to the myometrial segments occurs
stic • This process replaces the endothelial lining and
the muscular arterial wall by fibrinoid formation
invasion • This physiological change transforms spiral
of uterine arterioles into low resistance, low pressure, high
flow system
vessels • In preeclampsia there is failure of the second
wave of endovascular trophoblast migration and
there is reduction of blood supply to the
fetoplacental unit
 • Maternal immune intolerance to paternally
derived placental & fetal antigens

• Formation of blocking antibodies may be

impaired
Immunolog
ical • In women destined to be preeclamptic extra
Factors villous trophoblasts express reduced amounts of
immunosuppressive non-classic HLA (HLA G)

• There are more T-helper type 1 (Th1) expression

than Th2 (normal pregnancy have Th2 bias) in
preeclampsia
 ● In response to ischemia or other inciting
causes, placental factors are released in
maternal circulation and begin a cascade of
events that leads to oxidative stress
Endotheli
al Cell ● Antiangiogenic, metabolic and
Activatio inflammatory leucocyte factors are thought
to provoke systemic endothelial cell injury
n
● Cytokines such as TNF-α and the ILs may
contribute to the systemic oxidative stress
 Systemic
oxidative Activation of systemic
stress microvascular coagulation
manifested by
ROS and free thrombocytopenia
radicals

Generation of highly Greater systemic

toxic radicals capillary permeability
reflected by edema
and proteinuria
● Injure systemic vascular
endothelial cells
● Modify nitric oxide production
● Interfere with prostaglandin
balance
 • Preeclampsia : Multifactorial and polygenic

• Incidence of Preeclampsia : More common

among daughters, sisters & twins of
preeclamptic mothers
Genetic
Factors • Genes involved :
1. MTHFR
2. Factor V Leiden
3. ACE
4. NOS3
 1. Vasospasm :
• Results from systemic endothelial activation causing
subsequent hypertension

• Simultaneously there is endothelial injury leading to

Pathogen interstitial leakage

esis
• Maldistribution of blood flow leads to ischemia,
necrosis, hemorrhage & end organ disturbances

• Clinical correlation – marked attenuated blood

volume
 2. Endothelial Cell Injury:
• Protein factors likely placental secreted
into maternal circulation provoke
activation & dysfunction of systemic
vascular endothelium
Pathogen • Intact endothelium has anticoagulant
esis properties & by releasing “NO” also
blunt the response of vascular smooth
(Cont.) muscle to vasopressors

• Injured or activated endothelial cells

may produce less “NO” and may secrete
substances that promote coagulation
and greater sensitivity to vasopressors
 3. Increased Pressor Response:
• Normal Pregnancy : Usually a balance between
vasopressors & vasodilators

• In Preeclampsia : Imbalance of vasodilators (PGI2,

NO) and vasoconstrictors (Angiotensin-II, TXA2,
Pathogene Endothelin- I)

sis (Cont.)
• In Preeclampsia :
i. Prostacyclin : Thromboxane A2 ratio declines
ii. Decreased NO synthesis
iii. Increased Endothelin-1 a potent vasoconstrictor
 4. Angiogenic and Anti-angiogenic Proteins:
• Placental vasculogenesis depends on pro-
angiogenic (PLGF, VEGF) & anti-angiogenic
factors (sFlt-1 and sEng). In Preeclampsia the
angiogenic balance is disturbed
• Trophoblast of women destined to develop
Pathogene preeclampsia overproduces at least two
sis (Cont.) antiangiogenic peptides that enter the maternal
circulation: sFlt-1 and sEng
• Rise in sFlt-1 reduces PLGF and VEGF leading to
endothelial dysfunction and anti-angiogenesis
• Ratio of sFlt-1 and PLGF and sEng can be used as
predictor for Preeclampsia in second trimester
 • Cardiovascular System:

Greater cardiac afterload caused by

hypertension
Pathophysiol
Cardiac preload is diminished due to
ogy
diminished volume expansion

Endothelial activation leading to inter-

endothelial extravagation of fluid into
extracellular space specially lungs
 • Haemodynamic Changes and Cardiac Function:

Cardiac output declines partly due to increased

peripheral resistance

Diastolic dysfunction in 40-45%

Pathophysiology
If coexists with concentric ventricular hypertrophy from
(Cont.) chronic hypertension - May develop cardiogenic edema

Aggressive hydration may result in hyperdynamic

ventricular function and pulmonary edema may develop;
which is aggravated by presence of epithelial leak and
decreased oncotic pressure
• Blood Volume:
Haemoconcentration is hallmark of preeclampsia-
This is due to generalized vasospasm & leakage of
plasma into interstitial space. Degree of
haemoconcentration varies with severity- maximum
in eclamptic mothers
Clinically this haemoconcentration is very sensitive
to blood loss particularly during labor

• Thrombocytopenia:
Overt thrombocytopenia due to immunological or
simply platelet deposition at endothelial damage
site is described when platelet count falls below106/
µL : Severe disease
• Hemolysis
 Increased serum LDH

Decreased serum Haptoglobin

Presence of schizocytes, spherocytes & reticulocytes on

PBS

Cause: Microangiopathic hemolysis caused by endothelial

disruption with platelet adherence and fibrin deposition

Hemolysis, elevated liver transaminases and

thrombocytopenia -> HELLP syndrome
 • Coagulation changes: Depends on severity
of complication
• Elevated factor VIII consumption

• Elevated D-dimers

Pathophysiolo • Reduced levels of protein C, S & antithrombin III

gy (Cont.)
• Fibrinogen level do not fall unless complicated
by abruptio

• However routine assessment of coagulation

profile NOT required
 • Kidney:
In normal pregnancy renal blood flow & GFR rises
In Preeclampsia renal perfusion & GFR is reduced
due to higher renal arteriolar resistance
Pathophysiolo Glomerular endotheliosis further blocks the barrier
that allow filtration
gy (Cont.) Diminished filtration rises serum creatinine
Urine sodium conc.& osmolality rises,also urine:
plasma creatinine ratio increases
Plasma uric acid conc. is elevated due to ↓ in GFR
and ↑ tubular reabsorption
 • Acute Kidney Injury:

Clinically apparent acute tubular necrosis is

Pathophysiolo almost invariably due to co-morbid hemorrhage
gy (Cont.) hypovolemia and hypotension usually caused by
obstetric bleeding

Irreversible renal cortical necrosis is rare

 • Liver:
Periportal hemorrahage in the liver periphery
Serum transaminases are elevated
Pathophysiolo Clinically presents with acute right upper
gy (Cont.) abdominal or epigastric pain
Thrombocytopenia and features of hemolysis
may be associated (HELLP Syn.)
Large hematoma may rupture
 HELLP :
● This is an acronym for Hemolysis (H), Elevated Liver
enzymes (EL) and Low Platelet count (LP)

● This is a rare complication of preeclampsia (10–15%).

HELLP syndrome may develop even without maternal
hypertension
Pathophysiolo
● This syndrome is manifested by nausea, vomiting,
gy (Cont.) epigastric or right upper quadrant pain along with
biochemical & hematological changes

● Complications: Eclampsia(6%), Placental abruption(10

%), AKI (5%) & pulmonary edema(10%). Stroke, hepatic
hematoma, coagulopathy, acute respiratory distress
syndrome & sepsis were other serious complications
 HELLP :
● In Tennessee Classification - Diagnostic criteria for
HELLP are haemolysis with increased LDH (> 600
U/L), AST (≥ 70 U/L) & platelets < 100 x 109/L .It
may be Total HELLP or Partial HELLP .

Pathophysiolo ● The Mississippi Triple-class HELLP System further

classifies the disorder by the nadir platelet counts:
gy (Cont.)
○ Class1: Platelets ≤ 50x 109/L, AST or ALT ≥
70 IU/L, LDH ≥ 600 IU/L
○ Class 2: Platelets ≤ 100x 109/L but ≥ 50x
109/L, AST or ALT ≥ 70 IU/L, LDH ≥ 600 IU/L
○ Class 3: Platelets ≤ 150x 109/L but ≥ 100x
109/L, AST or ALT ≥ 70 IU/L, LDH ≥ 600 IU/L
• Brain:
 Pathophysiology - Two theories:
1. Acute severe hypertension -> cerebrovascular overregulation ->
vasospasm
2. Sudden elevation of BP ->exceed normal auto-regulatory capacity -> rise in
end capillary pressure - > vasogenic edema
Results:
1. Cortical , subcortical petechial & intracerebral hemorrhage
2.Vasular lesion – fibrinoid necrosis of the arterial wall and perivascular
microinfarcts and hemorrhage
3. Posterior reversible encephalopathy syndrome (PRES) typically affect
occipital and parietal lobe
4. Generalized cerebral edema
Clinical presentation:
Headache with scotomata, Convulsion, Blindness, Mental status changes,
Coma
 • Visual Changes and Blindness:
Scotomata, blurred vision, diplopia, blindness
(usually reversible)

Three areas usually involved -> Occipital lobe,

Lateral geniculate body & Retina
Pathophysiolo
gy (Cont.) Occipital blindness due to vasogenic edema ->
Amaurosis -> resolved completely

Retinal blindness-> serous retinal detachment

(reversible) rarely retinal detachment (Purtscher
retinopathy) causes permanent vision loss
 • Placental perfusion and vascular testing: Roll
over test, isometric contraction test,
angiotensin infusion pressure response, uterine
Doppler velocimetry
• Feto-placental unit endocrine test: HCG, AFP,
PAPP-A
Prediction • Renal dysfunction: Serum uric acid,
Microalbuminuria, urinary calcium
• Endothelial dysfunction : PlGF, VEGF, sFlt-1,
sEng, platelet count
• Others : cfDNA
At present promising are - > sFlt:PlGF and
Uterine Artery Doppler Study
 • Dietary & Lifestyle modification: ↓ Salt intake,
Regular exercise, Bed rest (?) & Cardio protective
fatty acids – Limited role
• Calcium supplementation – Has a role in calcium
deficient population
• Antihypertensive Drugs: No role
• Antioxidants: Vitamin C,D,E, Statins, Metformin have
Prevention been tried
• Antithrombotic Agents: LMWH (no role), whereas it
is found that low-dose aspirin prophylaxis initiated
before 16 weeks’ gestation is associated with 10-
60% risk reduction for PE & FGR. Aspirin (75 to 150
mg) daily, effectively inhibits platelet thromboxane
A2 biosynthesis but has minimal effects on vascular
prostacyclin production
 C/F
Managem • Asymptomatic – Majority of patients
• Hypertension usually diagnosed during routine ANC
ent of • Enquire ominous signs – headache, blurring of vision,
gestationa vomiting, epigastric pain & oliguria
l • Assess edema,weight, gestational age ,uterine height &
liquor volume ,fetal movement & FHS
hypertensi • Management as per duration of pregnancy & severity of
on HT
Degree of HTN HTN 140/90-159/109` Severe HTN
>160/110

Admission Not routine admit

Antihypertensive Give if >140/90 Give to all women

Target 135/85 Target135/85

BP Measurement Once or twice a week Daily 3-4 times a day

Dipstick Once or twice a week Daily

Blood tests CBC,LFT,KFT weekly Weekly

PlGF based test 1 occasion 1 occasion

Fetal Assessment FHS every visit FHS every ANC

USG fetal assessment every 2-4 wks USG ever 2 wks
CTG only if clinically indicated CTG at diagnosis & if indicated
 • Antihypertensive: Labetolol (choice), Nifedipine or
Methyldopa
• Timing of Birth: Not planned before 37 weeks if BP
<160/110
• Pregnancy not to be prolonged (i.e. > 40wks)
Managem • If early birth needed - Consider antenatal
corticosteroids (if less than 34 weeks) & MgSO4
ent • Intranatally - Maintain partograph & monitor BP
(Cont.) frequently
• Do AMTSL as per protocol - Treat PPH promptly,
avoid hypotension & hypovolemia
• Postnatally - BP to be monitored, Hypertensive to be
continued, Methyldopa to be withdrawn & a
medical follow-up after 2 weeks
 Management of Preeclampsia depends on :

Severity of preeclampsia
Managem
ent of Duration of pregnancy

Preeclamp Response to treatment

sia Any clinical sign that cause concern &

Suspected fetal compromise

 Severe hypertension
Degree of hyoertension Non-severe hypeertension BP 140/90-159/110
BP >= 160/110

Admission Admit if any clinical concern for well being of baby or mother Admit

Antihypertensive Offer if BP>=140/90 Offer

Target135/85 Target 135/85

BP Monitoring Every 48 hrs Every 15-30 min till it is less than 160/90
More frequently if admitted

Dipstick Only repeat if indicated Only repeat if indicated

Blood parameters CBC,LFT, KFT twice a week Three times a wk

Fetal assessment FHS in all ANC FHS in every ANC

USG every 2 wks USG at diagnosis and every 2 wks
CTG at diagnosis then if indicated CTG at diagnosis then if indicated
 • For in-patients:
A CBC with platelet estimate, creatinine, LDH, AST,
ALT & testing for proteinuria should be obtained in
parallel with a comprehensive clinical maternal &
fetal evaluation
Managem Fetal evaluation should include USG evaluation for
estimated fetal weight & volume of amniotic fluid,
ent as well as fetal antepartum testing
Antihypertensives: Increase the dose & add second
(Cont.) or third drug if needed
Consider parenteral antihypertensives (Labetolol,
Hydralazine), Nitroglycerin transdermal patch,
Sodium Nitroprusside in hypertensive emergency
crisis
Counseling regarding condition and timing of birth
 • Timing of birth: Thresholds for early delivery
irrespective of gestational age-

Inability to control BP despite use of 3 or more

Managem antihypertensive
Maternal pulse oximetry <90%
ent Progressive deterioration of liver function,
(Cont.) kidney function, hemolysis or platelet count
Ongoing neurological features like headache,
visual scotomata or eclampsia
Placental abruption
Reversed end-diastolic flow in UA doppler, non-
reassuring CTG or still birth
Weeks of pregnancy Timing of birth
Before 34 weeks Continue surveillance unless there are
indications for planned early birth. Offer
intravenous magnesium sulfate and a
course of antenatal corticosteroids

From 34 to 36+6 weeks Continue surveillance unless there are

indications for planned early birth. When
considering the option of planned early
birth, take into account the woman's and
baby's condition, risk factors (such as
maternal comorbidities, multi-fetal
pregnancy) and availability of neonatal unit
beds. Consider a course of antenatal
corticosteroids if required

37 weeks onwards Initiate birth within 24–48 hours

Management (Cont.)

All cases of severe PE should receive MgSO4 prophylaxis for prevention

of convulsion

The rate of seizures in preeclampsia with severe features without

magnesium sulfate prophylaxis is four times higher than in those
without severe features (4 in 200 versus 1 in 200)

It has been calculated that 129 women need to be treated to prevent

one case of eclampsia in asymptomatic cases, whereas in symptomatic
cases the number needed to treat is 36
Algorithm of
Managemen
t of Severe
Pre-
eclampsia
 Postnatally

• Monitor BP

• Start or continue antihypertensive

Managem
ent • Enquire neurological pre-monitoring symptoms

(Cont.) • Discharge - BP is controlled, no symptoms of

preeclampsia & blood test results are stable or
improving

• Follow up after 2 wks

Complications of Preeclampsia
• Neurological • Hematological
• Cerebral Edema • Thrombocytopenia
• Confusion and mental changes • HELLP Syndrome
• CVA and Cerebral hemorrhage • DIC
• Placental
• Vision • Abruption
• Reversible impairment of vision • Placental Insufficiency
• Rarely , permanent loss of vision • Intrapartum
• Cardiopulmonary • PPH
• Pulmonary Edema • Instrumental Delivery
• Liver • LSCS
• Periportal Haemorrhage • Fetal
• Sub capsular hematoma • FGR
• Fetal Distress
• Kidney • Meconium Aspiration
• Acute Kidney Injury • Still birth
 Hypertensive disorder may serve as
Future Pregnancy markers for subsequent preterm labor and
growth restriction

Women who develop Preeclampsia or GH

are at greater risk for same in future
pregnancies

Overall risk of recurrence in future

pregnancy is approximately 1 in 5

Overall increase risk of cardiovascular

diseases in later life
 Define Pre-Eclampsia. Enumerate the causes and high
risk factors of Pre-Eclampsia. Describe shortly the
pathological changes in different organs

A 25 year young lady P0+0 come to OPD with 32 weeks

of pregnancy and her BP found to 150/100 mmof Hg.
Questions

How will proceed to diagnose the condition. How will

you manage the case

A 25 year young lady P0+0 come to OPD with 34 weeks

of pregnancy and her BP found to 150/100 mm of Hg.
With2+ proteiunria. How will proceed to diagnose the
condition. How will you manage the case
Questions

Write Short Notes on

• Prediction of Pre-Eclampsia
• Management of Severe Pre-Eclampsia
• Theories of Pre-Eclampsia
• Prevention of Pre-Eclampsia
• Anti-hypertensives used in Pre-eclampsia
• Renal Changes in Pre-Eclampsia
• Cerebral Changes in Pre-Eclampsia
• Visual Changes in Pre-Eclampsia
• Placental remodeling in Pre-Eclampsia
Questions
Justify - Pre-Eclampsia is not a preventable disease

Justify - Eclampsia is Preventable

Justify - Judicious volume replacement in hypovolemia is absolute necessary in Pre-Eclampsia

Syndrome
Justify - All Pre-Eclampsia mother should undergo Fundoscopy examination

Justify - All severe Pre-eclampsia mother should receive prophylactic MgSO4

Justify - Preeclampsia in 1st pregnancy will not give immunity for preeclampsia in future pregnancies
THANK
YOU