Hypertensive Disorders in Pregnancy

2.01 09/26/16
Dra. Florentina Villanueva
20 1 8
OUTLINE PREECLAMPSIA SYNDROME
Terminologies and Diagnosis
Preeclampsia Syndrome
Incidence
Risk Facto
Etiopathogenesis
Abnormal Trophoblastic Invasion
Nutritional Factors
Pathogenesis
Systemic Effects:
CVS
Hemodynamic changes and cardiac function
Blood Volume
Hematologic Changes
Volume Homeostasis
Kidney, Liver, Pancreas
Brain
Prediction and Prevention
Management
Consideration for delivery
Eclampsia
Management
Persistent Postpartum Hypertension

TERMINOLOGIES AND DIAGNOSIS

Complicate 5 to 10 percent of all

pregnancies
One member of the deadly triadalong
HYPERTENSIVE
with hemorrhage and infection
DISORDERS
WHO- 16 percent of maternal deaths
More than half of these hypertension-
related deaths are preventable
Systolic BP 140 or diastolic BP 90
mmHg for first time during after
midpregnancy
No proteinuria
BP returns to normal before 12 weeks
GESTATIONAL
postpartum (transient hypertension)
HYPERTENSION
Final diagnosis made only postpartum
50% subsequently develop
preeclampsia syndrome proteinuria,
epigastric discomfort or
thrombocytopenia
a convulsion that cannot be attributed to
another cause in a woman with
ECLAMPSIA preeclampsia
seizures are generalized and may
appear before, during, or after labor
diagnosed in women with documented
blood pressures 140/90 mmHg before
CHRONIC pregnancy or before 20 weeks
HYPERTENSIVE gestation, or both
DISORDER Hypertension first diagnosed after 20
weeks gestation and persistent after 12
weeks postpartum
New-onset proteinuria 300 mg/24
hours in hypertensive women but no
proteinuria before 20 weeks gestation
Sudden increase in proteinuria or BP or
platelet count < 100 000/L in women
PREECLAMPSIA with hypertension and proteinuria before
SUPERIMPOSED 20 weeks gestation
ON CHRONIC **Blood pressure normally decreases
HYPERTENSION during the second and early third
trimesters in both normotensive and
chronically hypertensive women
develops earlier in pregnancy more
severe and accompanied by fetal-growth
restriction
pregnancy-specific syndrome that can
affect virtually every organ system
gestational hypertension with proteinuria
PREECLAMPSIA
Proteinuria- objective marker
SYNDROME
Reflects the system -wide endothelial
weak, which characterizes the
preeclampsia syndrome
*See last page for Tab le 40-1
INCIDENCE
1. young and nulliparous (3-10%) vulnerable to developing
preeclampsia
2. older women (variable to < nulliparous) greater risk for
CHVD
3. race and ethnicity genetic predisposition
> 11% African American
> 9% Hispanic
> 5% white
RISK FACTORS
1. Obesity
-relationship between maternal weight and the risk of
preeclampsia is progressive
BMI < 20 kg/m 2 = 4.3%
BMI > 35 kg/m 2 = 13.3%
2. Multifetal gestation =13% (singleton 6%)
3. Maternal age
4. Hyperhomocysteinuria
5. Metabolic syndrome
6. Women with PE in the first pregnancy are at greater
risk during a second pregnancy
ETIOPATHOGENESIS
Gestattional hypertensive disorders are more likely to develop in
women with the following characteristic
1. Exposed to chorionic villi for the first time
2. Exposed to a superabundance of chorionic villi, as with
twins or hydatidiform mole
3. Have preexisting conditions of endothelial cell activation or
inflammation such as diabetes or renal or cardiovascular
disease
4. Genetically predisposed to a hypertension developing
during pregnancy
A fetus is not a requisite for preeclampsia to develop.
Although chorionic villi are essential, they need not be
intrauterine
The cascade of events leading to the preeclampsia syndrome
o Abnormalities that result in vascular endothelial
damage with resultant vasospasm
transudation of plasma, and ischemic and
thrombotic sequelae

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PHENOTYPIC EXPRESSION OF PREECLAMPSIA SYNDROME NUTRITIONAL FACTORS

- caused by faulty
endovascular trophoblastic Potential benefit of antioxidants to prevent preeclampsia
STAGE 1
remodeling that downstream Supplementation with vitamins E (-tocopherol) and C
MATERNAL PE
causes the stage 2 clinical (ascorbic acid) to prevent preeclampsia proven
syndrome unsuccessful
- susceptible to modification Diet high in fruits and vegetables with antioxidant activity
by preexisting maternal is associated with decreased blood pressure
conditions that are manifest Calcium supplementation in populations with a low dietary
by endothelial cell activation calcium intake had a small effect to lower perinatal
STAGE 2
or inflammation mortality rates but no effect on PE incidences
PLACENTAL PE
- cardiovascular or renal
disease, diabetes, obesity, PATHOGENESIS
immunological disorders, or
hereditary influences Vasospasm

Endothelial activation causes:

ABNORMAL TROPHOBLASTIC INVASION 1. Vascular constriction with resistance
2. Interstitial leakage through which blood constituents
including platelets and fibrinogen, are deposited
subendothelial

maldistribution, ischemia of the surrounding tissues lead

to necrosis, hemorrhage, and other end-organ disturbances
characteristic of the syndrome

small blood vessels in the nail beds, ocular fundi, and bulbar
conjunctiva
Endothelial Cell Injury
Normally Physical Examination
- Intact endothelium has Damaged or activated endothelial
anticoagulant cells
properties 1. May produce less nitric oxide
- Endothelial cells blunt 2. Secrete substances that
the response of promote coagulation and
vascular smooth increased sensitivity to
muscle to agonists by vasopressor
releasing nitric oxide 3. Changes in glomerular
1. normal placental implantation proliferation of extravillous
capillary endothelial
trophoblasts from an anchoring villus
morphology]
4. Increased capillary
2. trophoblasts invade the decidua and extend into the walls
permeability
of the spiral arteriole to replace the endothelium and
5. Increased blood
muscular wall to create a dilated low-resistance vessel
concentrations of
substances associated with
3. WITH PE defective implantation characterized by
endothelial activation
incomplete invasion of the spiral arteriolar wall by
extravillous trophoblasts results in a small caliber
Nitric Oxide
vessel with high resistance to flow
- a potent vasodilator synthesized from L-arginine by
* the magnitude of defective trophoblastic invasion is thought to endothelial cell
correlate with severity of the hypertensive disorder - decreased NO synthesis:
o increased mean arterial pressure
o decreased heart rate
o reverses the pregnancy-induced refractoriness to
vasopressors
Endothelins
- potent vasoconstrictors
- Endothelin-1 (ET-1) primary isoform produced by
human endothelium
NORMAL: increased plasma ET- 1 levels
PE+ higher plasma ET-1 levels

TREATMENT
Preeclamptic women are treated with magnesium sulfate
lowers ET-1 concentrations

Angiogenic and antiangiogenic proteins

Abnormally narrow spiral arteriolar lumen impairs
placental blood flow hypoxic environment release of
placental debris or microparticles that incite a systemic
inflammatory response
Decreased soluble antiangiogenic growth factors may be
involved in faulty endovascular remodeling
*DIAGRAM PATHOPHY (see last page)
Gestational HPN, PE syndrome:
- Preterm deilivery
- Growth-restricted fetus
- Placental abruption
TRANSCRIBERS: [EDIT] Person 1, Person 2, Person 3
Placental vasculogenesis evident by 21 days after
conception
Vascular endothelial growth factor (VEGF) and
angiopoeitin (Ang)
Angiogenic imbalance describes excessive amounts of
antiangiogenic factors that are hypothesized to be
stimulated by worsening hypoxia at the uteroplacental
interface
Soluble Fms-like tyrosine kinase (sFlt-1)- variant of the
Flt-1 receptor for placental growth factor (PIGF) and for
VEGF
Soluble endoglin (sEng)
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Cardiovascular System obstetrical hemorrhage, and it occasionally causes
1. Increased cardiac afterload caused by hypertension hepatic failureso-called shock live
2. Cardiac preload, which is affected negatively by Aymptomatic elevations of serum hepatic transaminase
pathologically diminished hypervolemia of pregnancy and 2 nd levelsAST and ALTare also considered markers for
is increased by intravenous crystalloid or oncotic solutions severe preeclampsia
3. Endothelial activation with interendothelial extravasation of Hemorrhagic infarction may extend to form a hepatic
intravascular fluid into the extracellular space and 3 rd hematoma
importantly, into the lungs Form a subcapsular hematoma that may rupture
Acute fatty liver of pregnancy is sometimes confused
Hemodynamic Changes and Cardiac Function with preeclampsia
1. modifiers hypertension severity, underlying chronic 4th
Hypertension, elevated serum transaminase and
disease, preeclampsia severity, and in which part of the creatinine levels, and thrombocytopenia
clinical spectrum
2. peripheral resistance = CO
3. Myocardial function- diastolic cardiogenic pulmonary
Pancreas
edema (alveolar endothelial-epithelial leak) decreased
1. No convincing data that the pancreas has special
oncotic pressure from a low serum albumin concentration involvement with preeclampsia syndrome
2. Severe hemoconcentration may predispose to pancreatic
Blood Volume
inflammation
1. Hemoconcentration has been a hallmark of eclampsia
generalized vasoconstriction that follows endothelial Brain
activation and leakage of plasma into the interstitial space
Cerebrovascular Pathophysiology
because of increased permeability
1. Response to acute and severe hypertension,
2. Vasospasm and endothelial leakage of plasma may
cerebrovascular overregulation leads to vasospasm
persist for a variable time after delivery
ischemia, cytotoxic edema, and eventually tissue infarction
3. Substantive cause of this fall in hematocrit is usually the 2. Sudden elevations in s ystemic blood pressure exceed the
consequence of blood loss at delivery normal cerebrovascular autoregulatory capacity regions
of forced vasodilation and vasoconstriction develop
Hematological change
increased hydrostatic pressure, hyperperfusion, and
1. Platelet count- routinely measured in women with any form
extravasation of plasma and red cells through endothelial
of gestational hypertension tight-junction openings vasogenic edema
2. Overt thrombocytopenia
- defined by a platelet count < 100,000/uL
Neurological Manifestations
- indicates severe disease
1. Headache and scotomata arise from cerebrovascular
3. Delivery- advisable
hyperperfusion that has a predilection for the occipital lobe
4. Other platelet abnormalities: a. platelet aggregation (due 2. 20-30% visual changes preceding exclamptic convulsion
to platelet exhaustion); b. immunological processes or 3. Convulsion: excess ive release of excitatory
simply platelet deposition at sites of endothelial damage
neurotransmittersespecially glutamate; massive
5. Neonatal thrombocytopenia: severe thrombocytopenia
depolarization of network neurons; and bursts of action
does not develop in the fetus of infant born to preeclamptic
potentials
women despite severe maternal thrombocytopenia 4. Generalized cerebral edema: mental status changes that
6. Hemolysis: manifest by elevated serum LDH levels and vary from confusion to coma
decreased heptoglobin level; schizocytosis, spherocytosis,
and reticulocytosis in peripheral blood
Visual changes and blindness
7. HELLP Syndrome: Hemolysis, Elevated Liver enzyme,
1. Scotomata, blurred vision, or diplopia
Low Platelet 2. Usually improves with magnesium sulfate therapy and/or
lowered blood pressure
Volume Homeostasis
3. Blindness is less common, is usually reversible
1. extracellular fluid, manifest as edema endothelial injury
4. Retina, pathological lesions may be ischemia, infarction,
and reduced plasma oncotic pressure
or detachment
2. Electrolyte concentrations do not differ appreciably 5. Occipital blindness is also called amaurosis
3. Not the case in- vigorous diuretic therapy, sodium 6. Blindness from retinal lesions is caused either by serous
restriction, or administration of free water with sufficient
retinal detachment or rarely by retinal infarction, which is
oxytocin to produce antidiuresis
termed Purtscher retinopathy
Kidney Cerebral Edema
1. renal perfusion and glomerular filtration: may result from
1. Worrisome
reduced plasma volume
2. Symptoms ranged from lethargy, confus ion, and blurred
2. Glomerular endotheliosis blocking the filtration barrier
vision to obtundation and coma
3. urine sodium concentration and creatinine and uric acid
3. Lethargy, confusion and blurred vision to obtundation and
level coma
4. Prerenal mechanism- urine osmolality, urine plasma 4. Careful blood pressure control is essential
creatinine ratio, and fractional excretion of sodium
5. Mannitol or dexamethasone
5. Proteinuria:
a) may develop late, and some women may already
Long-term neurocognitive sequelae
be delivered or have had an eclamptic convulsion Some cognitive decline
before it appears
b) Dipstick qualitative determinations
PREDICTION AND PREVENTION
c) 24-hour quantitative specimen, the consensus
threshold value used is > 300 mg/24 hr
d) Urinary protein:creatinine ratio
6. Acute Kidney Injury
Acute tubular necrosis - rare
Clinically apparent renal failure is invariably induced by
coexistent hemorrhage with hypovolemia and hypotension
Rarely, irreversible renal cortical necrosis develops

Liver
1. Periportal hemorrhage in the liver periphery
2. Hepatic infarction accompanied hemorrhage
Symptomatic involvement is considered a sign of
severe disease
Moderate to severe right-upper quadrant or
1 st midepigastric pain and tenderness
Increased aspartate aminotransferase (AST) or
alanine aminotransferase (ALT)
Infarction may be worsened by hypotension from

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MANAGEMENT 2. Neonatal complications, including respiratory distress,
More frequent prenatal visits if preeclampsia is suspected intraventricular hemorrhage, and death, were decreased
significantly when betamethasone was given.
Basic management objectives 3. Glucocorticoids might aid treatment of the laboratory
1. Termination of pregnancy with the least possible trauma to abnormalities associated with HELLP syndrome
mother and fetus
2. Birth of an infant who subsequently thrives
3. Complete restoration of health to the mother ECLAMPSIA
Generalized tonic-clonic convulsions
**Precise knowledge of fetal age Maternal complications
1. Placental abruption
EVALUATION 2. Neurological deficits
3. Aspiration pneumonia
1. Detailed examination 4. Pulmonary edema
2. Weight determined daily 5. Cardiopulmonary arrest
3. Analysis for proteinuria or urine protein: creatinine ratio on 6. Acute renal failure
admittance and at least every 2 days thereafter 7. Death
4. Blood pressure readings Facial twitching, rigidity with muscular contraction (15 -20
5. Creatinine, hepatic aminotransferase, hemogram, BUA, secs coma)
LDH, coagulation studies, NST, BPS Fever >39 oC is a grave sign of CNS hemorrhage
6. Evaluation of fetal size and well-being and amnionic fluid Increased urine output after delivery: sign of improvement
volume Proteinuria/edema disappear within a week
BP normalizes in 2 weeks postpartum
GOALS OF MANAGEMENT
Early identification of worsening preeclampsia Blindness
Development of a management plan for timely delivery Retinal detachment
Occipital lobe infarct or ischemia
Reduced physical activity
Psychosis
Further management depends on Lasts for 2 weeks and disappears thereafter
1. Preeclampsia severity
Prognosis is good
2. Gestational age
Treatment: Chlorpromazine or Haloperidol
3. Condition of the cervix
Differential Diagnosis
CONSIDERATION FOR DELIVERY
Epilepsy
1. Termination of pregnancy only cure for PE Encephalitis
2. Headache, visual disturbances, or epigastric pain are Meningitis
indicative that convulsions may be imminent, and oliguria Cerebral tumor
is another ominous sign Hysteria
Ruptured cerebral aneurysm
The prime objectives
1. Forestall convulsions Prognosis
2. Prevent intracranial hemorrhage and serious damage Serious
to other vital organs Overt threats to maternal life
3. Deliver a healthy newborn
MANAGEMENT
Magnesium sulfate is highly effective in preventing convulsions

TENETS
1. Control of convulsions
2. Intermittent administration of an antihypertensive
medication
3. Avoidance of diuretics
4. Delivery of the fetus to achieve a remission of
preeclampsia

Therapeutic level: 4-7 meq/L

Disappearance of patellar reflex: 10 meq/L
Respiratory arrest: 12 meq/L
Antidote:
Calcium Gluconate 1 gm IV
D/C MgSO4
Tracheal intubation
Mechanical ventilation

MANAGEMENT OF SEVERE HYPERTENSION

5 mg given every 20 min, maximum of 5
doses
HYDRALAZINE
satisfactory response: DBP 90-100
GLUCOCORTICOIDS maternal tachycardia and palpitations
1. To enhance fetal lung maturation, glucocorticoids have 20 mg IV initially followed by 40 mg in 20
been administered to women with severe hypertension minutes and then 80 mg every 20
who are remote from term LABETALOL
minutes if needed up to a maximum 300
mg dose
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maternal hypertension and bradycardia
10 mg orally (repeated in 30 min) Complications
NIFEDIPINE 1. heart failure
sublingual route is no longer recommended
VERAPAMIL IV infusion of 5-10 mg/hr 2. renal insufficiency
NIMODIPINE Continuous infusion or oral 3. abruption placenta
NITROPRUSSIDE Continuous infusion: 0.25/kg/min 4. fetal growth restriction
NIMODIPINE Fetal cyanide toxicity may develop after 4 5. fetal death
NITROPRUSSIDE hours
FUTURE PREGNANCIES
Before delivery, diuretics are not used to lower
DIURETICS
blood pressure higher risk to develop hypertension in future pregnancies
earlier preeclampsia is diagnosed during the index
PERSISTENCE POSTPARTUM HYPERTENSION pregnancy, the greater the likelihood of recurrence
preterm delivery and fetal-growth restriction in the first
Persistence maybe due to: pregnancy significantly increased the risk of preeclampsia
1. underlying chronic hypertension in the second pregnancy
2. mobilization of edema fluid into intravascular compartment
3. older and obese women
4. develop superimposed preeclampsia

PATHOPHYSIOLOGICAL CONSIDERATION IN THE DEVELOPMENT OF HYPERTENSION (Doc: araling mabuti)

MATERNAL VASCULAR DISEASE FAULTY PLACENTATION EXCESSIVE TROPHOBLAST

GENETIC, IMMUNOLOGIC OR INFLAMMATORY FACTORS

REDUCED UTEROPLACENTAL PERFUSION

VASOACTIVE AGENTS: NOXIOUS AGENTS:

Prostaglandins Cytokines
Nitric oxide ENDOTHELIAL ACTIVATION
Lipid peroxidases
Endothelins

CAPILLARY LEAK
VASOSPASM ACTIVATION OF
COAGULATION

Edema Proteinuria
Seizures
Thrombocytopenia
Oliguria
Hemoconcentration
Liver
ischemia Abruption

Hypertension

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