Hypertensive Disorders in Pregnancy

Mohammad Sohail Khan

Tasbeeh ur Rehman

Ayub Medical College

Hypertension in Pregnancy

Systolic B.P. > 140 mmHg

and/or

Diastolic B.P. > 90 mmHg

Documented on two occasions

At least 6 hours apart

Not more than 7 days apart

Incidence

Hypertensive disorders are among the most significant & still now unresolving problem complicating almost one in ten pregnancies

Responsible for 16% of Maternal Mortatlity in developing countries

Classification

Hypertension in Pregnancy

Pregnancy Induced Hypertension (PIH)

Preeclamsia-Eclampsia

Chronic Hypertension

Preeclamsia superimposed on Chronic Hypertension

What is Significant Proteinuria in Pregnancy

Total protein in 24 hours urine > 300mg

Pregnancy Induced HypertensionNew onset of hypertension after

20 weeks of gestation without proteinuria, followed by return of B.P. to normal within 6 weeks post-partum.

Preeclamsia

New onset of hypertension after 20 weeks of gestation along with properly documented proteinuria, followed by return of B.P. to normal within 6 weeks post-partum.

PreeclamsiaPregnancy Induced

HypertensionProteinuri

a

Eclampsia

Generalized tonic-clonic seizure in a patient with Preeclampsia not attributed to any other cause.

Eclampsia Preeclampsia

Seizure/Convulsion

/Coma

Chronic Hypertension in Pregnancy Hypertension before pregnancy /

Diagnosed before 20 weeks of pregnancy not due to gestational trophoblastic disease.

Hypertension diagnosed after 20 weeks but persistent after 6 weeks postpartum

Chronic HTN & Pregnancy :

Etiology :1. Essential HTN (Most Common)

2. Secondary HTN :

1. Genetic: Glucocorticoid remediable aldosteronism, Liddle Syndrome

2. Renal : Parenchymal, Renovascular

3. Endocrine : Primary hyperaldosteronism, cushing syndrome,

Pheochromocytoma

4. Vascular : Aortic coarctation, Estrogen use

5. Others

Superimposed Preeclampsia On Chronic Hypertension

New onset proteinuria in hypertensive women after 20 weeks' gestation

A sudden increase in proteinuria or blood pressure or platelet count < 100,000/L after 20 weeks’ gestation in women with hypertension and proteinuria before 20 weeks' gestation

Risk Factors

Genetic

Age & parity

Partner factors

Pregnancy Factors

Underlying Medical

Conditions

Others

Risk Factors

Risk Factors: Cont.

Genetic

Genetic Predispositio

n

Family History

Race & Ethnicity

More Common in

black & Asians

Pregnancy by ovum donation

Age &Parity

Teenage pregnancy

Age>35 yrs

Long interval between

pregnancy

Nulliparity

Partner Factors

Change of partner

Limited sperm

exposure

Pregnancy by donor

insemination

Partner fathered an eclamptic pregnancy

Risk Factors: Cont.

Pregnancy Factors

Multiple pregnancy

Hydatiform mole

Hydrops fetalis

Fetal chromosomal

anomaly(trisomy 13)

Underlying Medical Diseae

Chronic hypertension

Diabetes mellitus

Renal Disease

Cardiovascular disease

Hyperthyroidism

Sickle cell disease

Others

Obessity

Psychological stress & strain

Previous history of

preeclamsia

PATHOPHYSIOLOGY

2 stage model for preeclampsia

Stage 2Maternal syndrome

(HTN, proteinuria,Endothelial dysfunction)

Stage1Reduced placental

implantation???

Stage-1 Reduced placental

implantation – PREDISPOSING FACTORS:

Abnormal implantation

Association with microvascular diseases (diabetes, hypertension etc.)

Association with large placentas (hydrops, multiple gestation, hydatidiform mole)

Net effect

Replacement of endothelial lining & muscular arterial wall by fibrinoid formation

Distended tortuous spiral arteries

Low resistence, low pressure high flow system

uterine artery DOPPLER

In preeclamptic mother:Showing early diastolic NOTCHDecreased EDF(due to high resistance)

In normal mother

ETIOLOGICAL FACTORS

Placental hypoxia

Immunological factors

Placental enzymes

Genetic factors (MTHFR, F5,)

Oxidative stress

???????????????????

What causes maternal syndrome

Stage 2Maternal syndrome

(HTN, proteinuria,Endothelial dysfunction)

Stage1Reduced placental

implantation???

What gets into maternal circulation??????

stage-IIMaternal Syndrome

not just hypertension and proteinuria

But also involves different end organs

Physiology of maintained uteroplacental flow in Normal pregnancy

Placenta releases angiotensinase destruction of angiotensin-II(a potent vasoconstrictor) BP stabilized

Vascular synthesis of PGI-2 and NO in excess vasodilation BP stabilized & uteroplacental flow maintains

Release of VEGF restores uteroplacental flow

Normal balance of agonist & anta-gonistic factors:

1.vasodialator & vasoconstrictor

2. angiogenic and antiangiogenic factors

1.vasodialator & vasoconstrictor

vasodialator

NO

PGI-2

vasoconstrictor

Angiotensin-II

Endothelin-I

placenta

Syncytiotrophoblast &

endothelium

2. angiogenic and antiangiogenic factors

VEGFTFG-betaPDGF

ANGIOGENIC

ANTIANGIOGENICsFlt-1 (VEGFR-1)VEGFR-2Tie-1Tie-2

Pathophysiology for different organ damage

Basic mechanism of different organ damage:

Increased vasoconstriction Decreased organ perfusion : Increased endothelial dysfunction –

capillary leak, oedema, Pulmonary oedema, proteinuria.

Activation of coagulation: DIC, low platelets

Haemoconcentration

Organ damage

utero-placenta IUGR

Hematological Epistaxis, DIC like features, hemoconcentration

CNS Cerebral edema, cerebral hge seizures

Heart Subendothelial hge , focal necrosis & hge, cardiomyopathy, heart failure

Lungs Pulmonary edema, hemorrhagic brochopneumonia

Kidneys glomerular endotheliosis, oliguria

liver Subcapsular hge, ischaemiaperiportal necrosis, HELLP

CVS involvement:

• ↑afterload↑ed peripheral

resistance

• ↓preload ↓ed pregnancy

induced hypervolumia

•Pulmonary leak edemaalveolar endothelial

damage & ↓ed plasma oncotic pr

•hemoconcentration & ↑ed hematocrit

↓ed blood volume than normal

pregnancy(16% vs 50%):

Heart failure

↓cardiac output

Hematological system

Thrombocytopenia & other PL abnormality:

• ↑ed PL activation & degranulation,

• ↓ed life span. • Corelates well

wth disease severity.

Intravascular hemolysis

• endothelial damage & altered fluidity of erythrocyte membrane d/t change in serum lipid content → ↑ed LDH, spherocytosis, reticulocytosis

• microangiopathic hemolysis

↑ed coagulation & fibrinolysis

• Feature like DIC• Release of

thromboplastin• ↓fibrinogen• AT-III• plasminogen

Renal system involvement: ↓ed renal perfusion :(d/t ↓ed blood volume &

↑ed afferent arteriolar pr.) ↓ed GFR : d/t

glomerular capillary endotheliosis Endothelial dysfunction + mesangial swelling +

BM disruption (but podocyte disruption minimal)

Oliguria

↑ed creatinine level

↑ed uric acid

Hepatic involvement:

Periportal hemorrhage

hematoma

formation

Rupture

epigastric pain

Brain involvement:

Acute severe HTN

cerebrovascular overregulation

Vasospasm

Parenchymal ischemia

Cytotoxic edema

sudden ↑↑SBP

exceeds normal range of cerebrovascular autoregulation

Forced vasodilation + hyperperfusion

Vasogenic edema

Lungs involvement:

High SBP

↑ed arteriolar pr

↑ed extravasation of blood into alveoli + rupture of arteriole

Pulmonary edema, hemorrhagic

brochopneumonia

Diagnosisof HDP

Diagnosing Preeclampsia-Eclampsia:• Blood pressure ≥ 140/90 mm of

Hg (at or after 20 weeks of gestation) on 2 occasions at least 6 hours apart during bed rest. (≥ 160/90 mm of Hg is severe disease)

• accompanied by one or more of:

o significant proteinuria

-urinary dipstick 2+-random urinary protein/creatinine ratio ≥ 30 mg/mmol-24 hour urine excretion ≥300 mg/24 hrs

o renal involvement

-serum creatinine ≥ 90 mmol/L or

-oliguria (<400 ml in 24 hrs)

o haematological involvement

-platelet count<1 lakh

o liver involvement -raised AST, ALT (>70

IU/l) -severe upper abdominal pain

o neurological involvement -severe headache -persistent visual

disturbances-hyperreflexia with

sustained clonus

-convulsions (eclampsia) -stroke

o pulmonary oedema o fetal growth restriction

o placental abruption

HELLP Syndrome: -Hemolysis:● LDH > 600 U per L● Abnormal PBS showing

schistocytes, burr cells.● Serum bilirubin ≥ 1.2 mg/dL

-Elevated Liver enzymes:● AST and ALT >70 IU/l

-Low Platelet count:● <1 lakh/cubic mm

History -special points• Patient Particulars: Age young or >35 yrs, nulliparity,

low SES -risk factors• Chief Complaints: Swelling of legs or other parts of

body (face, abdominal wall, vulva, or whole body and tightness of the ring on the finger.) Severe disease -Headache, visual changes, nausea, vomiting, abdominal or epigastric pain, and oliguria, insomnia, vaginal bleeding, seizures.

• Present Obstetric History: Onset, Duration, Severity of Htn/Proteinuria and H/o drug intake

• Past Obstetric History: H/o any hypertensive disorder of pregnancy with week of onset. Also note the interval since last pregnancy, gestational age at delivery. Any foetal complications.

• Past History: of pre-existing hypertension, renal disease, diabetes, thrombophilia, or thyroid disorder.

• Family History: of Htn, Preeclampsia, Diabetes, CVD

Physical Examination:● Obesity/BMI>35 kg/m2

● Weight (serial measurements): Gain in wt at the rate of >1 lb a week or >5 lbs a month in the later months of pregnancy may be the earliest sign of preeclampsia.

● Oedema (all sites): has to be pathological, meaning visible pitting edema demonstratable over the ankles after 12 hrs bed rest.

● Pulse (in all 4 limbs)

● B.P.:

○ right arm, sitting/supine, arm at level of heart, cuff length=1.5 times of arm circumference, diastolic BP is the disappearance of Korotkoff sounds (phase V)

○ taken on 2 occasions at least 6 hrs apart for confirmation of diagnosis.

● CVS examination: auscultation for heart rate, rhythm, splitting of S2, murmurs.

● Ophthalmic examination: retinal haemorrage, nicking of veins, arteriole/vein ratio 3:1 from 3:2, papilloedema

● Deep tendon reflexes: hyperreflexia/presence of clonus

Maternal Investigations:Tests may be abnormal even when BP elevation is minimal.

• Urine dipstick testing for proteinuria

o Quantitation by laboratory methods if ≥ 2+ on dipstick testing

o Urinary ACR(albumin-creatinine ratio) to detect significant proteinuria (≥30mg/mmol)

o 24 hour urine collection is not necessary in routine clinical management

• Routine Blood Examination: TLC, DLC, Peripheral Smear, BT, CT, Hb%

• Serum Urea, creatinine, electrolytes including lactate dehydrogenase (LDH) and uric acid.

• Liver function tests (LFT) -AST, ALT >70 IU/l

Fetal Investigations:

• Cardiotocograph (CTG)

• Ultrasound scan (USS) assessment of:

o fetal growth

o amniotic fluid volume (AFV)

o umbilical artery flow (Doppler)

Differential Diagnosis Pre-existing hypertension, New/gestational hypertension Pre-eclampsia Eclampsia Exacerbation of underlying renal disease/Superimposed pre-

eclampsia-eclampsia SLE

ΔΔ ECLAMPSIA -Epilepsy

-Intracranial haemorrhage/thrombosis

-meningitis

-cerebral malaria

-amniotic fluid embolism can mimic eclampsia.

Assessment of the severity of Gestational Hypertensive

Disorders

There are several indicators used to assess the severity

of PIH

Blood pressure

Proteinuria

Other associated abnormalities

N.B: Grades of proteinuria (in g/L): Trace=0.1, 1+=0.3, 2+=1, 3+=3, 4+=10

Hypertensive disorders

in Pregnancy

Gestational HTN

● BP ≥ 140/90mmHg ●No evidence of

underlying cause of HTN

●No associated symptoms

●Comes to normal within 6 wks of

delivery

Pre-eclampsia

Non Severe Severe

Eclampsia

PreEclamsia+

Convulsion±

Coma

N.B: Pre-eclampsia is principally a syndrome of signs and when symptoms appear it is usually

late.Assessment of the severity of pre-eclampsia is given in the

next slide.

Indicators of severity of Pre-eclampsia

ABNORMALITIES NONSEVERE (mild) SEVERE

Blood pressure ≥140/90mmHg but <160/110mmHg

≥160/110mmHg

Proteinuria ≤2+ ≥3+

Oliguria Absent <400ml/day

Headache Absent Present

Visual disturbances Absent Present

Platelet count Normal Thrombocytopenia (100,000/mm3)

HELLP syndrome Absent May be presentALT,AST >70 IU/LLDH>600 IU/LBilirubin >1.2g/L

Serum transaminases(AST,ALT)

Normal (<40 IU/L) Elevated

Epigastric pain Absent Present

Fetal growth restriction Absent Obvious

Pulmonary oedema Absent present

COMPLICATIONS OF PRE-ECLAMPSIA

IMMEDIATE

REMOTE

MATERNAL FETAL

● IUGR ● IUD ● Asphyxia ●Prematurity

During Pregnancy

During Labour

During puerperiu

m●Eclampsia(2%) (more in acute cases)●Accidental hemorrhage●Oliguria●Diminished vision●HELLP Syndrome●Cerebral hemorrhage●ARDS

● Eclampsia● Postpartum hemorrhage

●Eclampsia( in < 48hrs of delivery)●Shock ●Sepsis

●Residual hypertension●Recurrent pre-eclampsia●Chronic Renal Disease• Abruptio

placentae

COMPLICATIONS OF ECLAMPSIA

MATERNAL FETAL

●Asphyxia●Prematurity●Hypoxia & IUD

Injuries Systemic

●Tongue bite

●Injuries due to fall

●Bed sore

●PULMONARY: edema, pneumonia, ARDS, embolism

●CARDIAC: acute left ventricular failure

●RENAL: renal failure

●HEPATIC: necrosis, subcapsular hematoma

●CNS: cerebral hemorrhage, edema(vasogenic)

Vision

●Diminished vision due to retinal detachment or occipital lobe ischemia

Hematology

●Low platelet count

●Disseminated Intravascular Coagulation

Postpartum

●Shock●Sepsis●Psychosis

HELLP Syndrome

This is an acronym for Hemolysis (H), Elevated Liver enzymes (EL), and Low Platelet count (LP).

It is a rare multisystem disorder that complicates pregnancy with lab evidences of micro-angiopathic hemolysis, hepatic dysfunctioning & thrombocytopenia.

It is a complication mostly associated with Pre-eclampsia but can also be diagnosed (rarely though) in the absence of these disorders.

HEMOLYSIS(due to

passage of RBCs through

partially obstructed

vessel)

s)HEPATIC DYSFUNCTION

(due to intravascular

fibrin deposition & sinosoidal

obst.)

Decreased Liver

blood flow

HELLPSyndrome

THROMBO-CYTOPENIA

(due to platelet aggregation & diposition in the sites of

endothhelial damage)

PATHOGENESIS

Diagnosis

Hemolysis (Hallmark of the triad)

Elevated Liver Enzymes

Low Platelet Count

LDH>600IU/L Liver Enzymes (<100,000/cu.mm)

Low serum haptoglobin

High serum bilirubin (>1.2 mg/dl)

High ALT & AST(>70 IU/L)

Abnormal PBS (Schistocytes, burr cells) Later-low Hb%

• ●Epigastric /Right Upper Quadrant pain

• ●Nausea, Vomiting

1. Clinical Features:

2. Lab Investigation:

Treatment

Can we predict whether a pregnancy would be complicated with Hypertensive disorders?

Indirectly, YES…

Placental Perfusion/ Vascular Resistance related

TestsUterine Artery Doppler Velocimetry

Uterine Artery Doppler Velocimetry (abnormal flow resistance/ diastolic notch in 2nd/ 3rd trimester)

The efficacy of the preventive methods is questionable too…

The investigative procedures are cumbersome, time-consuming and expensive…

Management of preeclampsia & PIH

After early diagnosis, further management depends on …

Severity of disease

Fetal maturity

Condition of cervix

Treatment proper

For mild - controlled disease :

Thereafter induction may be done at term depending on cervical

condition

Can be managed expectantly till term at home/hospital and

continued till term.

61

Hospitalisation???

Gestational HTN : only if severe HTN

Preeclampsia : If diastolic pressure≥ 100mm of Hg OR, there is proteinuria OR, there is fetal compromise.37 completed weeks of gestation.

When should we use antihypertensive to control the BP???

   Acute management of severe hypertension (BP > 160/110: to prevent stroke) which may require parenteral therapy.

What are the options???

Acute

Hydralazine inj.: now available

Labetalol Injection

Nifedipine capsule/Tabl

et

Long term

Methyl Dopa 250 mg Tab.

Labetalol Tablet 100

mg

Nifedipine 5,10,20 mg

But wait…can antihypertensives be used in expectant management???In non-severe Pregnancy

hypertension – No clear Evidence of benefit other than to reduce The Frequency of Episodes of Severe hypertension

May Adversely Effect Fetal Growth velocity

For severe-uncontrolled disease:

Caesarian Section OR In case of very severe uncontrolled disease elective Caesarian Section may be done without induction

Preinduction Cervical ripening with prostaglandin/osmotic dilators

followed by induction

Termination is considered

66

If failed

For early onset severe preeclampsia:

Controversy regarding termination in early onset disease

But there is no beneficial role for mother, as well as perinatal mortality is also high instead of conservative management

So… 67

termination is seriously considered

Fetal considerati

ons

Prematurity

Stillbirth

Newborn asphyxia

Maternal considerati

ons

– Worsening of disease

Complications

DELIVERY CARE

For any HDP, vaginal delivery should be considered unless a CS is required for the usual obstetric indications.

Antihypertensives : continued throughout labour to maintain BP < 160/110 mmHg .

3rd Stage : actively managed with oxytocin 5 units IV or 10 units IM, particularly in the presence of thrombocytopenia or coagulopathy. (I-A)

Ergometrine should NOT be given

Management of Eclampsia :

Prompt delivery of fetus to achieve cure

Avoidance of diuretics & hyper osmotic agents

Limitation of I.V fluid

Intermittent antihypertensive to control BP judiciously

Control of convulsion by MgSO4 (IM/IV route)

Protection & supporting care during convulsionProtection in a railed cot

Protection of airway & prevention of tongue

bite

Correction of hypoxia & acidosis

70

to control convulsion

“It is the most effective drug to control even recurrent seizures without any central nervous system depression to mother & fetus”

71

Magnesium sulphate

Dosages

→Paralysing agent & Intubation

→Amobarbital 250mg I.V over 3 min

In case of uncontrolled recurrent seizure (10-15%) : →additional 2-4g of 20% solution IV @ <1g/min

→4gm of 20% solution IV slowly(@ <1g/min) + 10g of 50% solution deep IM in upper & outer quadrant of

buttock by a wide bore needle then 5g of 50% solution IM 4hrly similarly

IM regime (Pritchard protocol):1955

→4 gm loading in 100ml of IVF over 15-20 min followed by 2-3g/hr in 100 ml IVF as

maintenance

I.V regime (Sibai protocol):1990

IM doses are as active as IV doses in controlling seizures

72

S o m e mo re a b o u t Ma g n e s iu m

Duration : 24 hrs from last convulsion or from delivery which one is longer.(This is called Magnesium sulphate prophylaxis in severe preeclampsia.)

Features of toxicity:

i> Impaired breathing(@8-10meq/L)

ii>Arrythmia and Asystole ( @10-13 mEq/L)

iii>Decreased/absent deep tendon reflex

(Hyporeflexia at 4 mEq/L, loss of patellar reflex at 7-10 mEq/L)

iv> Shock (>13 mEq/L)

For a maintenance dose following must be present - Serum Mg level 4-7meq/l(twice daily) Having Patellar reflex Urine output >30ml/hr RR>12/min

73

WHAT If magnesium toxicity is suspected???

Administration of 10mL of 10% calcium gluconate (1 g in total) as a slow intravenous

push.

Serum magnesium level obtained.

Magnesium infusion should be discontinued, supplemental oxygen administered,

Thank You!!!