Hypertensive Disorders

PGI Sani Shrestha

AUF Medical Center

Williams Obstetrics 24th Edition1

Chapter 40

Patient Profile

JL, 22

G1P0

Filipino Angeles
City
Chief Complaint: Elevated BP

History of Present Illness

Few Hours
PTA

The patient came in for regular prenatal

checkup
(+) BP = 170/120
on monitoring
Persistence of elevated BP Admission

Patients History
Past
Medical
History

(-)
Hypertension
(-) Diabetes
Mellitus
(-) Asthma
(-) Allergy
(-) Hepatitis

Family
History
(+)Hypertension:
Mother
(-) Diabetes
Mellitus
(-) Asthma
(-) Cancer
(+) Heart disease

Personal
and Social
History

(-) Smoker
(-) Alcoholic bev.
drinker
Catholic
Unemployed
Single
College graduate

Obstetrics History
G1P0
G1 : Present pregnancy
LMP 01/31/14
EDC 10/07/14
AOG 32 6/7

Number of Prenatal Checkups: 8

1st Prenatal Checkup was during 6th week of A

OG

Gynecologic History
M=14 y/o

1st Sexual contact: 20

I= Regular, 28 day cycle

No. of Sexual Partners:

1

D= 5 Days
A= 3 ppd/Moderately Soaked
S= (-) Dysmenorrhea

(-) OCP use

(-) Post-Coital Bleeding
(-) Dyspareunia
(+) Pap Smear: 2014,
normal

PHYSICAL EXAMINATION
General: awake, conscious, coherent
Vital signs:
BP: 170/100 mm Hg PR: 72 RR: 18 Temp: 36.3oC
Height: 53
Pre-pregnancy Weight: 71 kg BMI= 27.7 kg/m2
Current weight: 87 kg BMI= 34 kg/m2
Total weight gain: 16 kg (35.4 lbs)

PHYSICAL EXAMINATION
HEENT: Pink palpebral conjuntivae, Anicteric sclerae
Lungs: Symmetrical chest expansion, (-) retractions, clear breat

h sounds

Heart: Adynamic precordium, (-) Murmur, Normal rate and re

gular rhythm

PHYSICAL EXAMINATION
Abdomen:

globular, non tender

FH: 27 FHT 130s EFW: 2480 kg

Leopolds maneuver: Not done

Speculum Exam: Smooth, pink, (-) erosions, (-) bleeding
Internal Exam: Cervix closed, mid position
Extremities: full and equal pulses, (-) edema

Initial CTG

B FHT: 135-140s, Minimal-Moderate variability, (-)

accelerations, (-) decelerations,
UC: mild contractions every 7-10 minutes

Initial Laboratory findings

UA
Yellow/sl turbid/

6.5/ 1.010
Sugar: -ve
Albumin: 4+
PC: 4-6
RBC: 0-2
EC: Mod
Bacteria: Mod

CBC

Clinical
Chemistry
BUN: 7.79

mg/dl
Crea: 0.96

mg/dl
LDH: 643.2

Hct: 0.41

Hb: 142

WBC: 12.64

Neutrophil: 0.82

Lymphocytes:
0.13

Monocytes: 0.05

Platelet: 93

u/L
K: 3.94mmol/L

N
SGPT/AST: 33.7
SGPT/ALT: 22.0

Admitting diagnosis
G1P0 Pregnancy uterine 32 6/7 weeks AOG, cep

halic, not in labor, severe preeclampsia

PLAN
Emergency Cesarean Section I

Initial management
Dexamethasone 6mg/IM q12 x 4 doses
MgSO4 4gm SIVP, 5gm/ IM each buttock
Hydralazine 5mg/IV

Final diagnosis
G1P1(0101) PU, preterm, cephalic, delivered via LSCS I

for non-reassuring fetal heart rate pattern (minimal var

iability) category II, to a LBBG BW 1.83 kg BL 44 cm A
S 8,9 NMR 32 weeks AGA, single nuchal cord coil, Abr
uptio placenta, severe preeclampsia

16

Hypertensive Disorders
Discussion

UA
Yellow/sl

turbid/ 6.5/
1.010
Sugar: -ve
Albumin: 4+
PC: 4-6
RBC: 0-2
EC: Mod
Bacteria: ModCBC

Hct: 0.41

Hb: 142

WBC: 12.64

Neutrophil: 0.82

Lymphocytes:
0.13

Monocytes: 0.05

Platelet: 93
17

Gestational hypertension
BP 140/90mmHg for first time during pregnancy
No proteinuria
BP returns to normal < 12 weeks postpartum
Final diagnosis made only postpartum
Almost develop preeclampsia syndrome:
headaches or epigastric pain, proteinuria,

and thrombocytopenia.
18

Preeclampsia
best

described as a pregnancy-specific syndrome that can affect vi

rtually every organ system.
BP140/90mmHg after 20weeks' gestation
Proteinuria

300mg/24hrs;
urine protein : creatinine ratio 0.3 or
Persistent 30mg/dl (1+dipstick) in random urine samples

overt

proteinuria may not be a feature in some women with the preeclampsi

a syndrome
(Sibai, 2009)

19

Indicators of Preeclampsia Severity

severe versus nonsevere.

Headaches or visual disturbances such

as scotomata

Epigastric or right upper quadrant pain

hepatocellular necrosis, ischemia, an
d edema
stretches Glisson capsule.
accompanied by elevated serum hepa
tic transaminase levels.
thrombocytopenia is also chara
cteristic of worsening preeclampsia
platelet activation and aggregation
microangiopathic hemolysis

Finally,

renal or cardiac involvement

20

Eclampsia
preeclampsia+convulsion

Seizures that cannot be attributed to other causes in woman with preecla

mpsia
Seizures are generalized and may appear before, during, of after labor

21

Preeclampsia Superimposed on Chro

nic hypertension
any chronic hypertensive disorder predisposes a woman to de

velop superimposed preeclampsia syndrome.

BP 140/90 mmHg before pregnancy or diagnosed before 20

weeks gestation or both

22

Incidence and Risk Factor

Young and nulliparous women : risk of preeclampsia,
older women are at greater risk for chronic hypertension with superimpose

d preeclampsia.

Other factors include environmental, socioeconomic, and even seasonal infl

uences

Nulliparous
3-10%

other risk factors include obesity, multifetal gestation, maternal age, hyperh

omocysteinemia, and metabolic syndrome (Conde-Agudelo, 2000; Scholte

n, 2013; Walker, 2000).

23

Incidence and Risk Factor

Maternal weight and the risk of preeclampsia is progressive.
BMI (Kg/m2)

Morbidity (%)

<20

4.3

>35

13.3

Gestation
twin
single

13
5
(Sibai, 2000)

Smoking during pregnancy reduced risk of hypertension du

ring pregnancy (Bainbridge,2005 ; Zhang, 1999)

Kraus and associates (2013) smoking upregulates placental

adrenomedullin e

xpression, which regulates volume homeostasis

24

25

Etiology
Hypertensive Disorders

Basic concepts
Exposed to chorionic villi for the first time
Exposed to a superabundance of chorionic villi, as with twins or

hydatidiform mole
Have preexisting vascular disease
Genetically predisposed to hypertension developing during pregna

ncy
26

 Vascular endothelial damage with vasospasm, transudation of p

lasma, and ischemic and thrombotic sequelae.

an imposing number of Mechanisms

Placental implantation with abnormal trophoblastic invasion of Uterine vessels

Immunological maladaptive tolerance between maternal, paternal (place

ntal), and fetal tissues

Maternal maladaptation to cardiovascular or inflammatory changes of
normal pregnancy
Genetic factors including inherited predisposing genes and epigenetic inf
luences.

27

Abnormal Trophoblastic Invasion

In normal implantation i

s characterized by extens
ive remodeling of the spi
ral arterioles within the
decidua basalis

Endovascular trophoblas

ts replace the vascular e

ndothelial and muscular
linings to enlarge the ves
sel diameter.

28

Abnormal Trophoblastic Invasion

In preeclampsia
Incomplete trophoblastic invasion,
decidual vessels, but not myometrial vessels, become lined with endovascular trophoblasts.

The magnitude of defective trophoblastic invasion of the spiral arteries correla

ted with the severity of the hypertensive disorder (2000, Madazli)

Using electron micorscopy

Endothelial damage
Insudation of plasma constituents into vessel walls
Proliferation of myointimal cells
Medial necrosis
Lipid and macrophage accumulates in myointimal cells
29

 Lipid-laden cells > atherosis (Hertig, 1945)

Obstruction of the spiral arteriolar lumen by atherosis may

impair placental blood flow

Placental perfusion > diminished

30

Immunological Factors
Theory
Formation of blocking antibodies of placental antigenic sites might be
impaired.
Number of antigenic sites provided by the placenta is unusually great
compared with the amount of antibody, as with multiple fetuses. (Bee
r, 1978)
Effective immunization by a previous pregnancy is lacking, as in first p
regnancies.
The immunization concept was supported by
their observations that preeclampsia developed less often in multiparas
who had a prior term pregnancy (Mostello, 2002; Trupin, 1996)
31

Endothelial Cell Activation

The decidua contains an abundance of cells that, when activa

ted, can release noxious agents. (Staff, 1999) -> mediators to pro
voke endothelial cell injury

Preeclamsia due to an extreme state of activated leukocytes in

the maternal circulation

(Faas, 2000)

Cytokines : TNF-a, interleukin oxidative stress (highly toxic radica

ls)

Injure endothelial cells,

modify their NO2 production, and
interfere with prostaglandin balance

32

Nutritional Factors
Zhang and associates (2002) reported that the incidence of p

reeclampsia was doubled in women whose daily intake of as

corbic acid was less than 85 mg.

According to the 2013 Task Force, in several trials, suppleme

ntation with the antioxidant vitamins C or E showed no ben

efits.

33

Genetic Factors
Ward and Taylor (2014) cite an incident risk for preeclampsia

of 20 - 40 % for daughters of preeclamptic mothers

the result of interactions of literally hundreds of inherited gene
s
Plasma-derived factors may induce some of these genes in pre
eclampsia (Mackenzie, 2012)

34

35

Pathogenesis

Vasospasm
Vascular constriction resistance and subsequent hyp

ertension

Maldistribution, ischemia of the surrounding tissues

blood flow necrosis, hemorrhage, and other e

nd-organ disturbances
36

Endothelial cell activation

Protein factor -likely placental are secreted into the maternal circu

lation

activation and dysfunction of the vascular endothelium.

Grundmann and associates (2008) have reported that circulating e

ndothelial cellCEClevels are elevated 4 fold in the peripheral b

lood of preeclamptic women.

Damaged or activated endothelial cells secrete substances

promote coagulation and increase the sensitivity to vasopressors
changes in glomerular capillary endothelial morphology
increasd capillary permeability
elevated blood concentrations
37

Prostaglandins
In preeclampsia
Endothelial prostacyclin (PGI2) production is decreased
Thromboxane A2 (TXA2) secretion by platelets is increased

Increased sensitivity to infused angiotensin II

vasoconstriction

Increased Pressor Responses

Nitric oxide
Synthesized from L-arginine by endothelial cells. (potent vaso

dilator)

Nitric oxide maintains the normal low-pressure vasodilated st

ate characteristic of fetoplacental perfusion

(Myatt, 1992)

Preeclampsia is associated with decreased endothelial nitric ox

ide synthase expression, which increases cell permeability

(Wan

g, 2004)

39

Increased Pressor Responses

Endothelins
Endothelin-1 (ET-1) :
potent vasoconstrictors
Produced by human endothelium
Plasma ET-1 is increased in normotensive pregnant women, b

ut women with preeclampsia have even higher levels (Ajne, 2

003 ; Clark, 1992)

40

Increased Pressor Responses

Angiogenic factors

Vascular endothelial growth factor (VEGF), Placental growth factor (PIG

F),
which secretion increases in normal pregnancy
Promote angiogenesis
Induce nitric oxide
Vasodilatory prostaglandins

Paradoxically, VEGF is increased in serum from women with preeclampsi

a, but its bioavailability is decreased (Baker, 1995 ; Simmons, 2000)

41

Antiangiogenic Proteins
Trophoblast during preeclampsia overproduces at least two antiangiogenic
peptides that enter the maternal circulation (Karumanchi, 2014):
Soluble

Fms-like tyrosine kinase 1 (sFlt-1)

a variant of the Flt-1 receptor for placental growth factor (PlGF) and for VEGF.
maternal sFlt-1 levels inactivate and circulating free PlGF and VEGF concentrati

ons leading to endothelial dysfunction (Maynard, 2003).

Soluble

endoglin (sEng)

a placenta-derived 65-kDa molecule that blocks endoglin, which is a surface corecep

tor for the TGF family.

Also called CD105, this soluble form of endoglin inhibits various TGF isoforms fro
m binding to endothelial receptors and results in endothelial nitric oxide-dependen
t vasodilatation (Levine, 2006; Venkatesha, 2006).
42

43

Pathophysiology

Cardiovascular System
Increased cardiac afterload caused by hypertension
Cardiac preload in preeclampsia
Pathologically diminished hypervolemia of pregnancy
Iatrogenically increased by iv crystalloid or oncotic solution
Extravasion into the extracellular space, especially the lung

44

Cardiovascular System
Hemodynamic Changes
Preeclampsia
Cardiac output elevated before hypertension developed than normal pregnancy.

With clinical onset of preeclampsia

Marked reduction in cardiac output.
Increased peripheral resistance.

By contrast, Gestational hypertension

Elevated cardiac outputs with development of hypertension.
45

Cardiovascular System
Blood volume
Blood volume in term
Normal pregnancy : 4500ml
Not pregnancy : 3000ml
Eclampsia : 1500ml is lost
Hemoconcentration in preeclampsia
Vasoconstriction and Endothelial dysfunction with vascular permeabili
ty.
Whereas, gestational hypertension have a normal blood volume (Silve
r, 1998)
46

Blood and Coagulation

Platelet
Thrombocytopenia life threatening
Severe disease : < 100,000/uL
Platelet count > indication of delivery > normal in 3-5 days,
Platelet activation, aggregation, consumption ->
penia (Harlow, 2002)

exhausion -> thrombocyto

HELLP syndrome : hemolysis (H) , elevated liver enzymes (EL), and low platel
ets (LP) (Weinstein, 982)
Neonatal thrombocytopenia
Severe thrombocytopenia does not develop in the fetus or infant born to preeclamptic women despite

severe maternal thrombocytopenia (Kenny, 2014; Pritchard, 1987).

47

Blood and Coagulation

Coagulation
factor VIII consumption, fibrinopeptides A and B and of d-

dimers

levels of regulatory proteinsantithrombin III and protein

C and S.
Fibronectin

Glycoprotein-vascular endothelial cell basement membrane

in Preeclampsia

48

Blood and Coagulation

Fragmentation Hemolysis
Severe preeclampsia LDH hemolysis
Peripheral blood change :
Schizocytosis, spherocytosis, reticulocytosis

Clinical
Chemistry

BUN: 7.79

mg/dl
Crea: 0.96

mg/dl
LDH: 643.2

u/L
K: 3.94mmol/L

microangiopathic hemolysis caused by

end 33.7
SGPT/AST:
othelial disruption with platelet adherence and fibrin depositio
SGPT/ALT: 22.0
n.
Na: 137.9

result in part from

increased erythrocyte membrane fluidity with HELLP syndrome

decreased long-chain fatty acid content in erythrocytes of preeclampti

c women
49

Volume Homeostasis
Fluid and Electrolyte Changes
ECF vol.

Pathologic retention : endothelial injury

Electrolyte concentration do not differ.
Electrolyte unbalance
Vigorous diuretic therapy
Sodium restriction
Administration of water with sufficient oxytocin to prod
uce antidiuretics.

50

Kidney
Renal perfusion and glomerular filtration (in preeclampsia)
Due to vasospasm
Decreased filtration Creatinine Level
Plasma uric acid concentration ,
due to reduction in glomerular filtration rate and enhanced tubular reabs
orption
increased placental urate production compensatory to increased oxidativ
e stress.
At the same time, preeclampsia is associated with diminished uri

nary excretion of calcium,

51

Kidney
Proteinuria
the consensus threshold value used is > 300 mg/24 h
Anatomical changes
Glomeruli : 20% enlarged
Glomerular capillary endotheliosis

Capillary endothelial swelling with subendothelial deposits of protein materials

Acute renal failure

Tubular necrosis, cortical necrosis -> oligouria, anuria, rapidly develped azotemia
of them : HELLP synd. , 1/3 placental abruption, most had postpartum hemor
rhage

52

Liver
symptomatic involvement
moderate to severe right-upper quadrant or midepigastric pain a

nd tenderness
elevated levels of serum aminotransferase
asymptomatic elevations of serum hepatic transaminase levels

AST and ALTare also considered markers for severe preec

lampsia.

hemorrhagic infarction may extend to form a hepatic hemato

ma.

53

Liver
HELLP syndrome
Hemolysis, Elevated Liver enzyme and Low Platelet
20% of severe preeclampsia and eclampsia
Adverse outcome : 40%
Other complication
Eclampsia (6%), Placental abruption (10%), ARF (5%), pulm

onary edema (10%), subcapsular liver hematoma (1.6%)

Other serious complications included stroke, coagulopathy, acut

e respiratory distress syndrome, and sepsis.

54

Brain
Common Symptoms:
Headache, visual disturbance associated convulsion (eclampsia)
Anatomical pathology
principal lesions found at autopsy of eclamptic women were cortical and sub
cortical petechial hemorrhages
major lesions include subcortical edema, multiple nonhemorrhagic areas of
softening throughout the brain, and hemorrhagic areas in the white matter.

55

Neurological Manifestations
headache and scotomata
to arise from cerebrovascular hyperperfusion that has a predilection for the occipital
lobes.
headaches may be mild to severe and intermittent to constant.
do not usually respond to traditional analgesia, but they do improve after magnesiu
m sulfate infusion
Convulsions
diagnostic for eclampsia.
excessive release of excitatory neurotransmittersespecially glutamate;
Massive depolarization of network neurons; and bursts of action potentials

blindness is rare with preeclampsia alone, but it complicates eclamptic c

onvulsions in up to 15 percent of women

generalized

cerebral edema may develop and is usually manifest by ment

al status changes that vary from confusion to coma.

56

Uteroplacental perfusion
Vasospasm ->
placental perfusion > perinatal mortality and morbidity
Measurement of uterine artery blood flow velocity has

been used to estimate resistance to uteroplacental blood

flow

57

58

59

Management
One of the most important clinical questions for successful
management is precise knowledge of fetal age.

The basic management objectives for any pregnancy complicated by preeclampsia are:
(1) termination of pregnancy with the least possible trauma to mother and fetus,
(2) birth of an infant who subsequently thrives, and
(3) complete restoration of health to the mother.

Consideration for Delivery

Termination

of pregnancy is the only cure for preeclampsia.

Headache, visual disturbances, or epigastric pain are indicative that convu

lsions may be imminent, and oliguria is another ominous sign.

Most recommend frequent performance of various tests to assess fetal wel

l-being as described by the ACOG (2012a)

nonstress test or the biophysical

Measurement of the lecithin-sphingomyelin (L/S) ratio in amnionic fluid

may provide evidence of lung maturity

60

Glucocorticoids for Lung Maturatio

n
In attempts to enhance fetal lung maturation, glucocorticoids

have been administered to women with severe hypertension w

ho are remote from term.

Neonatal complications, including respiratory distress, intrave

ntricular hemorrhage, and death, were decreased significantly

when betamethasone was given compared with placebo.

61

62

63

Management of Eclampsia
1. Control of convulsions using an IV administered LD of MgSO4 that is

followed by a maintenance dose, usually intravenous, of MgSO4

2. Intermittent administration of an antihypertensive medication to lower

blood pressure whenever it is considered dangerously high

3. Avoidance of diuretics unless there is obvious pulmonary edema, limit

ation of intravenous fluid administration unless fluid loss is excessive,

and avoidance of hyperosmotic agents
4. Delivery of the fetus to achieve a remission of preeclampsia

64

MgSO4 is NOT given to treat

hypertension.

65

Pharmacology and Toxicology

Magnesium sulfate USP is MgSO 47H2O and not simple MgSO4.
cleared almost totally by renal excretion
intoxication is unusual when the GFR is normal or only slightly decrease

d.

Eclamptic convulsions are almost always prevented or arrested by plasm

a magnesium levels maintained at 4 to 7 mEq/L, 4.8 to 8.4 mg/dL, or 2.

0 to 3.5 mmol/L.

66

Magnesium is anticonvulsant and ne

uroprotective
Some proposed mechanisms of action include:
1. reduced presynaptic release of the neurotransmitter glutamate,
2. blockade of glutamatergic N-methyl-d-aspartate (NMDA) receptors,
3. potentiation of adenosine action,
4. improved calcium buffering by mitochondria, and
5. blockage of calcium entry via voltage-gated channels
(Arango, 2006; Wang, 2012a)

67

MgSO4 Toxicity
Patellar reflexes disappear as plasma magnesium level reaches 10
mEq/L-about 12 mg/d
>10 mEq/L, breathing becomes weakened.
>12 mEq/L, respiratory paralysis and respiratory arrest follow
At 15 mEq/L, such high plasma levels, respiratory depression
developed that necessitated mechanical ventilation,

Treatment with calcium gluconate or calcium chloride, 1 g

intravenously, along with withholding further magnesium
sulfate, usually reverses mild to moderate respiratory
depression

68

Management of Severe Hypertension

The three most commonly employed are hydralazine, labetalo

l, and nifedipine

Drug

Mechanism

Dose

Comments

Labetolol

1- and
nonselective blocker

10 mg IV initially. Then 10 -80 mg

with increment of 20-40mg every
10 -15 minutes as needed and a
maximum dose of 220 mg per
treatment cycle.

maternal hypotension and

bradycardia

Hydralazine

Direct
vasodilator,
dilates arteriole
with less effect
on veins

5 mg IV or IM, then 5-10mg IV

15-20 min until a satisfactory
response

the most commonly used

antihypertensive agent
Causes maternal tachycardia and
palpitations

Nifepidine

calciumchannel
blocking agent

10-mg initial oral dose to be

repeated in 30 minutes if
necessary.

Nifedipine given sublingually is

no longer recommended.

69

Fluid Therapy
Lactated Ringer solution is administered routinely at the rate

of 60 mL to no more than 125 mL per hour unless there is un

usual fluid loss from vomiting, diarrhea, or diaphoresis, or, m
ore likely, excessive blood loss with delivery.

70

71

Thank you!!!