Hiii

[Link]
i fish iiialt's a a noun apart
Case IUGFR
igtY go weeksAOG

initiating it

Titty s iii postpartum

OR before
pregnancy

It ftp.t 944
p
owe A
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

INTRODUCTION However, if the BP is still elevated after 12 weeks postpartum 

 The central role of hypertension up to the present time has not been then the diagnosis would be chronic hypertension
discovered
 After so many years it became apparent that preeclampsia was  This type of hypertension is a diagnosis of exclusion because final
considered to be a syndrome of hypertension and this is only one diagnosis made only postpartum
important part of hypertension  Subsequently develop preeclampsia syndrome  proteinuria,
 The mechanism on which pregnancy would incite/aggravate epigastric discomfort or thrombocytopenia
hypertension up to the present time is still unsolved
Preeclampsia Syndrome Younger
Hypertensive Disorders  Pregnancy - specific syndrome that can affect virtually every organ
 Remain among the most significant and intriguing unsolved problems in system
obstetrics  Gestational hypertension with proteinuria
 Complicate 5 to 10 percent of all pregnancies  Proteinuria
 One member of the deadly triad - along with hemorrhage and infection o Objective marker
to be the cause of maternal morbidity and mortality o Reflects the system-wide endothelial leak, which characterizes
 WHO - 16 percent of maternal deaths were attributed to hypertensive the preeclampsia syndrome
disorders
 More than half of these hypertension-related deaths were preventable
If the patient only had a regular prenatal check-up, managed
accordingly  patient could have survived

 Most common medical complication encountered in pregnancy

 2nd most common cause of maternal mortality and an important cause
of perinatal mortality and morbidity
 Prevalent in young women of low socio-economic status without
prenatal care

What is Hypertension?
 BP of > 140/90 Lecture Discussion: Preeclampsia Syndrome
 Blood pressure must be manifested on at least 2 occasions taken 6 Preeclampsia Syndrome can be diagnosed even without the presence of
hours apart proteinuria
 Before, an increase of 30 mmHg systolic and 15 mmHg diastolic above In the absence of proteinuria or fetal growth restriction (IUGR), as long as
the BP taken at mid-pregnancy were used to diagnose hypertension there is multi-organ involvement  Preeclampsia Syndrome
o Example, even if you are not 140/90 ~ if your initial BP was  Thrombocytopenia
100/60 and then all of a sudden it became 130/75  this was  Renal Insufficiency
considered before as hypertensive disorder  Liver involvement
o But take note that this is no longer used to diagnose  Cerebral symptoms
hypertension BUT for those patient who would have an  Pulmonary edema
increase of 30 mmHg systolic and 15 mmHg diastolic should
NOTE: Remember that this should be diagnosed AFTER 20 weeks AOG
be monitored very closely because even if the BP is not 140/90,
there are instances that some patients will develop seizures or
Indicators of Severity of Preeclampsia Syndrome
eclampsia

Classification of Hypertension in Pregnancy

 Chronic hypertension
 Gestational hypertension
 Preeclampsia
 Chronic hypertension with superimposed preeclampsia
 Eclampsia
 Delta hypertension OF 1140190
sudden AinMAP
Gestational Hypertension
 Systolic BP >140 or diastolic BP >90mmHg for first time after
midpregnancy
After midpregnancy  means after 20 weeks AOG in the absence
of proteinuria

 No proteinuria
 BP returns to normal before 12 weeks postpartum (transient
Lecture Discussion: Indicators of Severity
hypertension)
You have to check the BP 12 weeks postpartum  means 3 months You would notice here that there are those considered as ominous sign (ex.
from the time the patient delivered. If BP returns to normal then it Headache, visual disturbances, upper abdominal pain)  this is part of the
is a transient hypertension 10 danger signs of pregnancy; patient would later develop seizure or
eclampsia

#GrindNation Page 1 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Preeclampsia with Severe Features Risk Factors continued…..

 BP ≥ 160 mm Hg SP or ≥ 110 mm Hg DP  Maternal age (too young , too old)
 Decreased platelet count  Hyperhomocysteinemia
 Oliguria, increased serum creatinine  Metabolic syndrome (ex. PCOS)
 Congestive HF, pulmonary edema  Women with PRE ECLAMPSIA in the first pregnancy are at greater
 Epigastric / RUQ pain, elevated liver enzymes risk in a second pregnancy
 Persistent headache, visual or cerebral disturbances  Pregnancy with male fetus in first pregnancy  you have slight risk
of developing hypertension
Eclampsia  Smoking during pregnancy  reduces the risk of hypertension
 A convulsion that cannot be attributed to another cause in a woman o However, smoking has many adverse pregnancy outcomes
with preeclampsia  HIV positive
↑ risk of hypertension
This means that you have to rule out other causes of seizure. The  Sleep breathing disorders (ex. Apnea)
only reason why she developed the seizure should be ONLY due to
the preeclampsia Preeclampsia other Risk Factors:
Immunologic Related
 Seizures are generalized and may appear before, during, or after labor  Nulliparous Mostimportantriskfactor
 Previous preeclampsia
Chronic Hypertensive Disorder  Multiple Gestation
 Diagnosed in women with documented blood pressures ≥ 140/90  Abnormal Placentation
mmHg before pregnancy or before 20 weeks’ gestation, or both
 Hypertension first diagnosed after 20 weeks’ gestation and persistent Disease Related
after 12 weeks postpartum  Chronic HTN
 Chronic Renal Disease
Preeclampsia superimposed on Chronic Hypertension Elderly  Collagen Vascular Disease
 New-onset proteinuria ≥ 300 mg/24 hours in hypertensive women but  Pregestational DM
no proteinuria before 20 weeks’ gestation
 Sudden increase in proteinuria or BP or platelet count <100,000/μL in Maternal Related
women with hypertension and proteinuria before 20 weeks’ gestation  African American
 ** Blood pressure normally decreases during the second and early third  Obesity
trimesters in both normotensive and chronically hypertensive women  35 < Age < 20
Sometimes chronic hypertension is very difficult to diagnose  New paternity
especially if you were not able to see the patient prior to 20 weeks
 Cohabilitation <1 year
AOG. Why? Basically, BP normally ↓ during 2nd and early 3rd
trimesters in both normotensive and chronically hypertensive
women  this what we called Physiologic Hypotension  during Family History
this time BP ↓ but after which the BP will ↑  Relatives
 Mother-in-law
 Develops earlier in pregnancy → more severe and often is
accompanied by fetal-growth restriction
ETIOPATHOGENESIS
INCIDENCE AND RISK FACTORS Gestational hypertensive disorders are more likely to develop in women with
Incidence the following characteristic:
 Young and nulliparous (3-10%) 1. Exposed to chorionic villi for the first time (primigravida)
o Vulnerable to developing preeclampsia (PE) 2. Exposed to a superabundance of chorionic villi, as with twins (multifetal
 Older women (variable but < nulliparous) pregnancy) or hydatidiform mole
o Greater risk for CHVD with Superimposed PE 3. Have preexisting conditions of endothelial cell activation or
 Race and ethnicity – genetic predisposition inflammation such as diabetes or renal or cardiovascular disease
o >11% African American 4. Genetically predisposed to hypertension developing during pregnancy
o
o
o
>9% Hispanics
>5% White
Black women has a greater tendency for maternal morbidity in
 A fetus is not a requisite for preeclampsia to develop Ironist
This means that molar pregnancy (regardless if it’s complete or

Q
comparison to Hispanic and White women partial)  prone to develop hypertension

Risk Factors  Although chorionic villi are essential, they need not be intrauterine
 Obesity Need not be intrauterine  means that even if ectopic pregnancy
o Relationship between maternal weight and the risk of can still develop hypertension
preeclampsia is progressive  this means that the higher the
BMI, the higher the chance of development of hypertension  The cascade of events leading to the preeclampsia syndrome are:
o BMI < 20 kg/m2 = 4.3% o Abnormalities that result in vascular endothelial damage with
o BMI > 35 kg/m2 = 13.3% resultant vasospasm → transudation of plasma, and ischemic
 Multifetal gestation = 13% > (singleton – 6%) and thrombotic sequelae
Regardless if the multifetal gestation is monozygotic, dizygotic,
mono- or di-chorionic  they are all prone to hypertension

#GrindNation
Strength in knowledge
i I Page 2 of 13
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Phenotypic Expression of Preeclampsia Syndrome Lecture Discussion: Abnormal Trophoblastic Invasion

Stage 1 – Placenta PE Abnormal

plantation 1st
Caused by faulty endovascular trophoblastic remodeling that
Normally in pregnant patient who are normotensive, normal implantation is
characterized by extensive remodeling of the spiral arterioles within the
downstream causes the stage 2 clinical syndrome decidua basalis. So the endovascular trophoblast in normotensive patient
would replace the vascular endothelial and muscular lining to enlarge the
Stage 2 – Maternal PE symptomatic

2nd3rd
Susceptible to modification by preexisting maternal conditions that are
vessel diameter  this would create a dilated low-resistance vessel

manifest by endothelial cell activation or inflammation Patients with preeclampsia  the decidual vessels but not the myometrial
 Cardiovascular or renal disease, diabetes, obesity, immunological vessel become lined with endovascular trophoblast. So the deeper
myometrial arterioles do not lose their endothelial lining and
disorders, or hereditary influences
musculoskeletal tissue (since no trophoblast do not traverse into the
myometrial vessels to cause the remodeling) that is why the external
Two Stage Model for Preeclampsia diameter is only half of that of the corresponding vessels in normal placenta
1st or Early 2nd Trimester Late 2nd or 3rd Trimester  There is incomplete invasion of the spiral arterioles by the
STAGE 1 STAGE 2 extravillous trophoblast  so what happens is that there will be a
 Abnormal PLACENTATION  MATERNAL Syndrome small-caliber vessel with high resistance of flow  blood vessel
 REDUCED Placental perfusion  There is already characteristic will constrict causing hypertension
hypertension, renal impairment,
proteinuria, etc. Abnormal Trophoblastic Invasion continued…..

(Asymptomatic Phase) (Symptomatic Phase) Early Preeclampsia changes:

1. Endothelial damage
2. Insudation of plasma constituents into vessel wall
3. Proliferation of myointimal cells
Etiology
4. Medial necrosis
Mechanisms:
1. Placental implantation with abnormal trophoblastic invasion of uterine
 Lipid accumulated first in myointimal cells and then within macrophage
vessel
→ Atherosis
2. Immunological maladaptive tolerance between maternal, paternal
 Vascular lesions in placentas from women diagnosed with preeclampsia
(placental), and fetal tissue
before 34 weeks
3. Maternal maladaptation to cardiovascular or inflammatory changes of
1. Spiral arteriole narrowing
normal pregnancy
2. Atherosis
4. Genetic factors including inherited predisposing genes and epigenetic
3. Infarct
influences

Abnormal Trophoblastic Invasion  Abnormally narrow spiral arteriolar lumen → impairs placental blood
flow → hypoxic environment → release of placental debris or
 Normal placental implantation
microparticles that incite a systemic inflammatory response
→ proliferation of extravillous
trophoblasts from an anchoring  Decreased soluble antiangiogenic growth factors may be involved in
villus faulty endovascular remodeling
 Defective placentation posited to further cause susceptible women to
 Trophoblasts invade the decidua
and extend into the walls of the develop: Gestational HPN, PE syndrome, preterm delivery, growth-
spiral arteriole to replace the restricted fetus, and placental abruption
endothelium and muscular wall
Immunologic Factors
to create a dilated low-
resistance vessel  Dysregulation - loss of maternal immune tolerance to paternally
derived placental and fetal antigen
o ** when the paternal antigenic load is increased, that is, with
two sets of paternal chromosomes – a “double dose.”
 With Preeclampsia → defective
implantation characterized by Lecture Discussion:
incomplete invasion of the spiral Preeclampsia is an immune-mediated disorder. Paternally derived
arteriolar wall by extravillous antigen can be a factor on its development which means that for
trophoblasts → results in a small- those patient wherein they have only 1 partner during their 1st and
caliber vessel with high resistance to subsequent pregnancies  they will be immunized after their 1st
flow pregnancy
 ** the magnitude of defective  Example, 1st pregnancy they had preeclampsia. The 2nd
trophoblastic invasion is thought to pregnancy  no more preeclampsia because they have
correlate with severity of the already been immunized to the paternal antigen after her
hypertensive disorder 1st pregnancy
 Another example, a woman is already on her 3rd pregnancy
BUT that pregnancy was due to another man (new partner)
 you will be again at risk of preeclampsia because it will
be a different paternal antigen

#GrindNation Page 3 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Immunologic factors continued….. Pathogenesis

 Acute graft rejection - histological changes at the maternal-placental  Vasospasm
interface o Endothelial activation causes
 Associated with dysregulation 1. Vascular constriction with ↑ resistance
o “Immunization” from a previous pregnancy 2. Interstitial leakage through which blood constituents,
o Some inherited human leukocyte antigen (HLA) and natural including platelets and fibrinogen, are deposited
killer (NK)-cell receptor haplotypes subendothelial  maldistribution, ischemia of the
o Possibly shared susceptibility genes with diabetes and surrounding tissues → lead to necrosis, hemorrhage,
hypertension and other end-organ disturbances characteristic of
 Immune maladaptation - extravillous trophoblasts early in pregnancy preeclampsia syndrome
express reduced amounts of immunosuppressive nonclassic HLA G o Small blood vessels in the nail beds, ocular fundi, and bulbar
 High levels of placental oxidative products conjunctiva
 Normal pregnancy – Th lymphocytes are produced so that type 2
activity is increased in relation to type 1 termed type 2 bias Normally…
THO o
o
Th2 cells → promote humoral immunity
Th1 cells → stimulate inflammatory cytokine secretion


Intact endothelium has anticoagulant properties
Endothelial cells blunt the response of vascular smooth muscle to
 Patients with PRE ECLAMPSIA = Th1 action is increased and the agonists by releasing nitric oxide
Th1/Th2 ratio changes (stimulated by placental microparticles and by  Endothelial cells normally release nitric oxide  a potent vasodilator
THO adipocytes)  since there will be increase inflammatory cytokine
secretion = disruption in placenta causing vasoconstriction and later on In Preeclampsia…
hypertension  Damaged or activated endothelial cells
1. May produce less nitric oxide
Endothelial Cell Activation
 III EYE ve
Inflammatory changes are believed to be a continuation of the stage 1
changes caused by defective placentation
2. Secrete substances that promote coagulation and ↑ sensitivity
to vasopressor
3. Changes in glomerular capillary endothelial morphology
 In response to ischemia or other inciting causes, placental factors are 4. Increased capillary permeability
released and would begin a cascade of events thus your antiangiogenic, 5. ↑ blood concentrations of substances associated with
metabolic factors, and other leukocyte mediators are thought to endothelial activation
provoke endothelial cell injury (endothelial cell activation)
Increased Pressor Responses
Endothelial cell injury provoke by:  ↑ vascular reactivity to infused norepinephrine and angiotensin II
1. Antiangiogenic and metabolic factors  ↑ sensitivity to angiotensin II clearly precedes the onset of gestational
2. Other inflammatory mediator hypertension
NORMOTENSIVE pregnant patients  they remain refractory to the
Oxidative stress associated with preeclampsia: effect of infused epinephrine and angiotensin 2
1. Tumor necrosis factor-α (TNF-α) HYPERTENSIVE pregnant patients  initially they are refractory to the
2. Interleukins (IL) effect of infused epinephrine and angiotensin 2 but as pregnancy
 Characterized by reactive oxygen species and free radicals → progresses they become more sensitive  if they are sensitive to these,
formation of self-propagating lipid peroxides it favors more vasoconstriction = hypertension develops more
 Generate highly toxic radicals that injure endothelial cells, modify
their NO production, and interfere with prostaglandin balance Prostaglandins
 Production of the lipid-laden macrophage foam cells seen in atherosis  ↓ endothelial prostacyclin (PGI2) production > mediated by
 Activation of microvascular coagulation manifest by phospholipase A2
thrombocytopenia  ↑ thromboxane A2 secretion by platelets
 Increased capillary permeability manifest by edema and proteinuria  ↓ prostacyclin:thromboxane A2 ratio
Prostacyclin – a potent vasodilator
Nutritional Factors Thromboxane A2 – for platelet aggregation
 ** Potential benefit of antioxidants to prevent preeclampsia
NORMOTENSIVE pregnant patients  there is higher production of
Up to this day, the only proven supplements to prevent prostacyclin than thromboxane A2
preeclampsia are: HYPERTENSIVE pregnant patients  they have higher thromboxane
 Calcium High dose A2 than prostacyclin = favor platelet aggregation = vasoconstriction =
 Aspirin hypertension development

 ** Supplementation with vitamins E (α-tocopherol) and C (ascorbic Nitric Oxide

acid) to prevent preeclampsia – proven unsuccessful  A potent vasodilator synthesized from L-arginine by endothelial cell
 Diet high in fruits and vegetables with antioxidant activity is associated  ↓ NO synthesis
with decreased blood pressure 1. ↑ mean arterial pressure
 Calcium supplementation in populations with a low dietary calcium 2. ↓ heart rate
intake had a small effect to lower perinatal mortality rates but no effect 3. Reverses the pregnancy-induced refractoriness to
on PREECLAMPSIA incidence vasopressors

#GrindNation Page 4 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Endothelial Cell Injury continued…..

Endothelins
 Potent vasoconstrictors
 Endothelin-1 (ET-1) - primary isoform produced by human endothelium
 Normal - ↑ Plasma ET-1 levels
 PRE ECLAMPSIA – higher Plasma ET-1 levels
In pregnancy, there is a normal elevation of ET-1 levels but despite
the elevation, vascular activity is not altered.
However, in preeclampsia there would higher levels of ET-1 
vascular activity altered  favors vasoconstriction  hypertension

 Treatment of preeclamptic women with magnesium sulfate lowers ET-

1 concentrations
Lecture Discussion: Effects of pro and anti-angiogenic factors in the vascular
Angiogenic and Antiangiogenic Proteins endothelium
 Placental vasculogenesis - evident by 21 days after conception
Proangiogenic factors: PLGF and VEGF
 Vascular endothelial growth factor (VEGF) and angiopoietin (Ang)  Maintains the smoothness of the endothelial walls
 During pregnancy, there should be a balance of angiogenic and  Maintains the modulated responses to vasoconstrictors
antiangiogenic proteins  Maintains the regulated permeability
 Angiogenic imbalance – describe excessive amounts of antiangiogenic  Thus there will be healthy vessels
factors that are hypothesized to be stimulated by worsening hypoxia at
the uteroplacental interface Antiangiogenic factors: sEndo and sFLT-1
o Soluble Fms-like tyrosine kinase 1 (sFlt-1)  Promotes adhesiveness & deposition of cells on the endothelial
 An antiangiogenic protein walls
 It is a variant of the Flt-1 receptor for placental growth  Promotes increases susceptibility of vessel walls to vasoconstrict
 Promotes increased permeability
factor (PlGF) and for VEGF
 Thus there will be defective vessels
 ↑ sFlt-1 would inactivate and reduce the circulating
antiangiogenic (VEGF and Ang) leading to endothelial
dysfunction
o Soluble endoglin (sEng)
 ↑ sEng contributes to the pathogenesis of
preeclampsia

Lecture Discussion: Pathophysiological considerations in the development of

hypertensive disorder due to pregnancy

Lecture Discussion: Stage 1 – Abnormal Placentation So in the presence of maternal vascular disease, faulty placentation, or
excessive trophoblast in combination of genetic, immunologic or
If there would be abnormal placentation, your placental growth factor (PlGF) inflammatory factors  it causes reduced uteroplacental perfusion leading
and vascular endothelial growth factor (VEGF) are pro-angiogenic factors to endothelial damage and activation

Soluble Fms-like tyrosine kinase 1 (sfLT-1) and endoglin are anti-angiogenic Endothelial activation would lead to:
factors  Vasospasm  there will be constriction leading to hypertension,
oliguria, liver ischemia, seizures and abruption
What is the role of these factors?  Capillary leak  leads to edema, proteinuria and
Proangiogenic factors – causes normal vascularity hemoconcentration
Anti-angiogenic factors – causes abnormal vascularity  Activation of coagulation  leads to thrombocytopenia

#GrindNation Page 5 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

PATHOPHYSIOLOGY Blood Volume

 Hemoconcentration has been a hallmark of eclampsia → generalized
vasoconstriction that follows endothelial activation and leakage of
plasma into the interstitial space because of increased permeability
Physiologically, women of average size would have a blood volume
increase of 3000 mL and during the last several weeks of pregnancy,
there would be an additional 1500 mL increase  at the end there
should be an increase of 4500 mL

So what happens to patients with preeclampsia or eclampsia?

The anticipated increase of 1500 mL is lost. They would only have
an elevation of 3000 mL  which is why they have
hemoconcentration

 Vasospasm and endothelial leakage of plasma may persist for a variable

Lecture Discussion: Pathophysiology of Preeclampsia & HELLP Syndrome time after delivery
Defects in placental perfusion – is the initial event in preeclampsia that  Substantive cause of this fall in hematocrit is usually the consequence
would lead to vascular endothelial dysfunction by mechanism that is unclear of blood loss at delivery
(up to the present time)
It has been suggested that the release of factors from the placenta in Hematologic Change all
response to ischemia would result in dysfunction of the endothelium in the  Platelet count - routinely measured in women with any form of
maternal circulation gestational hypertension
 Imbalance of the angiogenic factors leads to the development of
 Overt thrombocytopenia -defined by a platelet count < 100,000/μL—
preeclampsia and HELLP syndrome
indicates severe disease
o Delivery – advisable
o If there is already thrombocytopenia, this is already an
indication to terminate pregnancy regardless of maturity of the
baby
 Other Platelet Abnormalities
o ↓ platelet aggregation – due to platelet “exhaustion”
o Immunological processes or simply platelet deposition at sites
of endothelial damage
 Maternal thrombocytopenia is not an indication for cesarean delivery
 Neonatal Thrombocytopenia
o Severe thrombocytopenia does NOT develop in the fetus or
infant born to preeclamptic women despite severe maternal
thrombocytopenia
o Even if there is severe maternal thrombocytopenia  it would
Lecture Discussion: Pathophysiology of Preeclampsia not cause neonatal thrombocytopenia
 Hemolysis
Almost every organ is affected in cases of hypertension in pregnant patients.
o Manifest by:
Since there is vasoconstriction, there will be maldistribution of blood flow
 Elevated serum LDH levels Micwangropathic ane
which then leads to:
 Increased peripheral resistance  Decreased haptoglobin level
 Increased afterload o Peripheral blood smear will show:
 Left sided heart failure  which may left to congestive heart failure  Schizocytosis
(CHF) which may cause tachycardia and later on pulmonary edema  Spherocytosis
 Reticulocytosis
So with patients with severe preeclampsia, we should request for ECG and  HELLP Syndrome
Chest Xray o Hemolysis
 Example, on your PE auscultation you heard crackles (possible o Elevated Liver enzyme
congestion)  request ECG and CXR o Low Platelet

Cardiovascular System
1. Increased cardiac afterload caused by hypertension
2. Cardiac preload, which is affected negatively by pathologically
diminished hypervolemia of pregnancy and is increased by intravenous
crystalloid or oncotic solutions
3. Endothelial activation with interendothelial extravasation of
intravascular fluid into the extracellular space and importantly, into the
lungs

#GrindNation Page 6 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Pathophysiology continued….. Kidney

Coagulation Changes  ↓ renal perfusion and glomerular filtration  may result from reduced
 Subtle changes consistent with intravascular coagulation plasma volume
That’s why routine laboratory assessment of coagulation such as  Glomerular endotheliosis blocking the filtration barrier
prothrombin, aPTT, fibrinogen are NOT routinely required in the  ↑ urine sodium concentration and creatinine and uric acid level
management of pregnancy associated hypertensive disorder  Prerenal mechanism - Urine osmolality, urine:plasma creatinine ratio,
and fractional excretion of sodium
 Erythrocyte destruction  Proteinuria
 ↑ factor VIII consumption, fibrinopeptides A and B levels and D-dimers o Proteinuria is different in non-pregnant patients  proteinuria
 ↓ regulatory proteins—antithrombin III and protein C and S in them is protein excretion of 150 mg/day
 Plasma fibrinogen levels do not differ remarkably from levels found in o But in pregnant patients  proteinuria is protein excretion of
normal pregnancy >300 mg/day (this is due to the physiologic hyperfiltration
happening during pregnancy)
Volume Hemostasis o May develop late, and some women may already be delivered
Endocrine Changes or have had an eclamptic convulsion before it appears
 Normal pregnancy o Dipstick qualitative determinations 24-hour quantitative
o ↑ renin, angiotensin II, angiotensin 1–7, aldosterone, and specimen, the “consensus” threshold value used is >300
atrial natriuretic peptide, Deoxycorticosterone (DOC) mg/24 h
 Women with preeclampsia o Urinary protein:creatinine ratio ≥ 0.3 or persistent protein
o Retain sodium values of 30 mg/dl (1+ dipstick)
o Further ↑ Atrial natriuretic peptide

Fluid and Electrolyte Changes

 Extracellular fluid, manifest as edema
o Mechanism: Endothelial injury and reduced plasma oncotic
pressure
If there is endothelial cell injury  there will be interstitial
leakage = edema

 Electrolyte concentrations do not differ appreciably

 Not the case in - vigorous diuretic therapy, sodium restriction, or
administration of free water with sufficient oxytocin to produce
antidiuresis

Lecture Discussion: Preeclampsia effects on the Liver

Since there is decreased perfusion  there will be liver ischemia leading to
liver cell necrosis and release of liver enzymes (SGPT/ALT) into the blood
There will also be liver edema – where there is hydropic degeneration of the
liver cells  stretching of the Glisson’s capsule  leads to an ominous sign
of RUQ pain and liver rupture
Diagnostics:
 SGPT or ALT
 LDH

Liver
 Periportal hemorrhage in the liver periphery
 Hepatic infarction accompanied hemorrhage
 1st
Lecture Discussion: Preeclampsia effects on the Kidneys o Symptomatic involvement is considered a sign of severe
During normal pregnancy  there is ↑ renin = there would be vasodilatation disease
of the renal vessels = ↑ blood flow to kidneys = ↑ GFR = hyperfiltration  o Moderate to severe right-upper quadrant or midepigastric
reason why pregnant patients urinates more frequently pain and tenderness
BUT in preeclamptic patients  since there is vasoconstriction = there will o ↑ aspartate aminotransferase (AST) or alanine
be renal hypoperfusion = ↓ GFR = oliguria (less frequency of urination) aminotransferase (ALT)
 There will also be ↑ BUN, Creatinine, Uric acid o ** infarction may be worsened by hypotension from
 There will also be ischemic damage to the renal tissues leading to obstetrical hemorrhage, and it occasionally causes hepatic
proteinuria  ↓ IV oncotic pressure, ↑ hydrostatic pressure = failure—so-called shock live
edema
Nondependentedema
 Proteinuria can also cause ↓ serum albumin & ↑ urine protein
 2nd
o Asymptomatic elevations of serum hepatic transaminase
Diagnostics: levels—AST and ALT—are also considered markers for severe
 Serum creatinine – checks for urine protein preeclampsia
 Urine protein/Creatinine Ratio – for urine output monitoring

#GrindNation Page 7 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Liver continued….. Brain continued…..

 3rd Neurologic Manifestations
o Hemorrhagic infarction may extend to form a hepatic  Headache and scotomata - arise from cerebrovascular hyperperfusion
hematoma that has a predilection for the occipital lobe
o Form a subcapsular hematoma that may rupture  20 – 30% visual changes preceding eclamptic convulsion
 4th  Convulsion
o Acute fatty liver of pregnancy is sometimes confused with o Excessive release of excitatory neurotransmitters— especially
preeclampsia glutamate; massive depolarization of network neurons; and
o Hypertension, elevated serum transaminase and creatinine bursts of action potentials
levels, and thrombocytopenia  Generalized cerebral edema
o Mental status changes that vary from confusion to coma
Pancreas
 No convincing data that the pancreas has special involvement with Visual Changes and Blindness
preeclampsia syndrome  Scotomata, blurred vision, or diplopia
 Severe hemoconcentration may predispose to pancreatic inflammation  Usually improve with magnesium sulfate therapy and/or lowered blood
pressure
 Blindness is less common, is usually reversible Retina, pathological
lesions may be ischemia, infarction, or detachment
 Occipital blindness is also called amaurosis
 Blindness from retinal lesions is caused either by serous retinal
detachment or rarely by retinal infarction, which is termed Purtscher
retinopathy

Cerebral Edema
 Worrisome
 Symptoms ranged from lethargy, confusion, and blurred vision to
obtundation and coma
 Lethargy, confusion, and blurred vision to obtundation and coma
 Careful blood pressure control is essential
Lecture Discussion: Preeclampsia effects on CNS
 Mannitol or dexamethasone
Vasoconstriction will cause meningeal irritation  manifests as headache
 There will also be retinal ischemia  manifests as blurring of vision Long-term Neurocognitive Sequelae
 There will also be neuronal ischemia/irritation  manifests as 
Inition
Some cognitive decline
convulsions
 Too much vasoconstriction could also lead to cerebrovascular
accident (CVA) Mccann of death i
pre eclampsia
Diagnostics:
 Fundoscopy – refer them to the ophthalmologist

Brain
Cerebrovascular Pathophysiology
 Response to acute and severe hypertension, cerebrovascular
overregulation leads to vasospasm → ischemia, cytotoxic edema, and
eventually tissue infarction
 Sudden elevations in systemic blood pressure exceed the normal
cerebrovascular autoregulatory capacity → Regions of forced
vasodilation and vasoconstriction develop → increased hydrostatic
pressure, hyperperfusion, and extravasation of plasma and red cells
through endothelial tight-junction openings → vasogenic edema
Lecture Discussion: Preeclampsia effects on Uteroplacental Unit
Cerebral Blood Flow (CBF) If there will be placental injury  there will be fetal hypoperfusion  causes
 Autoregulation - mechanism by which cerebral blood flow remains IUGR, Oligohydramnios, FDIU (fetal death in utero)
 Diagnostics for this: UTZ and EFM
relatively constant despite alterations in cerebral perfusion pressure
 Preeclampsia
Decrease perfusion on placenta  vasoconstriction and hypoxia to the
o Significantly ↑ CBF implantation site  leads to abruptio placenta  DIC and Acute Renal
 Eclampsia Failure
o Cerebral hyperperfusion forces capillary fluid interstitially  Diagnostics: Coagulation Profile – to check for DIC
because of endothelial damage, which leads to perivascular
edema characteristic of the preeclampsia syndrome
o ** Posterior reversible encephalopathy syndrome

#GrindNation Page 8 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Uteroplacental Perfusion SCREENING AND DIAGNOSIS

 Compromised uteroplacental perfusion is almost certainly a major Risk Identification
culprit in the increased perinatal morbidity and mortality rate  Clinical history (risk factors)
 Measurement of uterine, intervillous, and placental blood flow would o Most important because just by getting a correct and complete
likely be informative. clinical history you could already identify patients who are at
 Measurement of uterine artery blood flow velocity Vascular resistance risk and have an idea on how to diagnose and manage them
is estimated by comparing arterial systolic and diastolic velocity  Physical examination findings
waveforms uterine artery “notching”—has been reported to be  Laboratory examination
associated with increased risks for preeclampsia or fetal-growth  Doppler velocimetry
restriction
Check for these in the history:
PREDICTION AND PREVENTION
Recommended Laboratory Evaluation & Rationale
 ≥ 70 IU/ml
Liver Enzymes
 > 2x the upper limit of normal
(SGPT/ALT)
 Preeclampsia-induced ischemic hepatocytes
Hematocrit  Increased (Hemoconcentration)
Hemoglobin  Anemia due to Microangiopathic Hemolysis
Platelet count  Thrombocytopenia (< 100,000/μl)
LDH  > 600 IU/L
Coagulation Profile  Protime
(DIC) - This is not routinely  Actual Platelet Count
requested unless indicated  D-dimer test
such as DIC  Fibrinogen test
 Schizocytes
Blood smear
 Spherocytosis Physical Examination Findings:
 Mean arterial Pressure (MAP)
HELLP Syndrome  Roll Over Test (ROT)
 Decreased haptoglobin (earliest) - <25 mg/dL o Done at 28-32 AOG because during these times, basically there
 Increased LDH - >600 IU/L is a decrease in BP of the pregnant woman
 PBS – damaged RBCs (schistocytes, burr cells) o To do this, you ask the pregnant woman to roll over the left
 Increased bilirubin (B1) - > 1.2 mg/dL lateral decubitus position (LLDP) and get the BP
 Decreased hemoglobin o After getting the BP on the LLDP, ask the patient to go supine
This reflects microangiopathic hemolytic anemia and get the BP after 5 mins.
o A difference of 20 mmHg on the diastolic BP of the LLDP from
Prediction supine position = (+) Roll Over Test
o If (+)  pregnant woman is 3x at risk of developing
preeclampsia
o Mechanism behind the roll over test:
 From LLDP there would be a greater blood volume
because the compression of the uterus is removed at
this position
 Supine position  there would be a decrease in blood
volume (compression of the uterus)
 A sudden decrease in blood volume could lead to
vasoconstriction due to hyperactivity of the vessels =
increased diastolic BP
 So an increase of 20 mmHg is a (+) Roll Over Test
Prevention

#GrindNation Page 9 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Regimens to Prevent Hypertension in Pregnancy continued…..

 No
o Progestogens
o Low salt intake
o Aerobic Exercises
o Vit C and E
o Bed rest
o Folic acid
o DHA/Fish oils

 Note: Only low dose aspirin and high dose calcium are proven to
prevent HTN in pregnancy
Placenta

MANAGEMENT
mall
More frequent prenatal visits if preeclampsia is “suspected.”
Lecture Discussion: Mean Arterial Pressure (MAP)  Basic management objectives
MAP = DBP + 1/3 (SBP –DBP) 1. Termination of pregnancy with the least possible trauma to
mother and fetus
If there would be a MAP increase of >90 mmHg during the 2nd trimester and
increase of >105 mmHg during the 3rd trimester  they are at risk of 2. Birth of an infant who subsequently thrives
pregnancy-induced hypertension and perinatal deaths 3. Complete restoration of health to the mother
 *** Precise knowledge of fetal age (AOG) is important because
ABSENCE of a mid-trimester drop in BP may predict future PIH based on the management depends here
absence of arteriolar vasodilatation
Early Diagnosis of Preeclampsia
Doppler Velocimetry Principle: Inclination IUGR finding
inUTZ
Clinical  Return visits at 7-day intervals at a minimum
 “A VISUAL TRANSLATION OF THE VELOCITY OF BLOOD FLOW IN A o New-onset diastolic blood pressures > 80 mm Hg but < 90 mm
VESSEL” Hg
 (+) Uterine artery notching (18-24 weeks): o Sudden abnormal weight gain of more than 2 pounds per week
o 50% will develop pre-eclampsia NOTE: Normal weight gain of pregnant woman is 1 pound
o 30% will develop IUGR per week. So if it becomes >2 pounds per week = monitor
 Clinical Significance: because she may be at risk of preeclampsia
o Detection rate for pre-eclampsia:
o Screening Tool: 
Admitted
1. Maternal history 46.5% o Overt hypertension, proteinuria, headache, visual
2. Uterine Artery Doppler 64.6% disturbances, or epigastric discomfort supervene.
3. History + Doppler 69.4% o Women with overt new-onset hypertension—either diastolic
BP ≥ 90 mm Hg or systolic BP ≥ 140 mm Hg
Regimens to Prevent Hypertension in Pregnancy o On admission of the pregnant patient do the ff. evaluation:
 Yes  Detailed examination,
o Low dose Aspirin
8018ing
Role of Low dose Aspirin:


Weight determined daily
Analysis for proteinuria or urine protein:creatinine
Thromboxane A2 favors vasoconstriction while ratio on admittance and at least every 2 days
AE Prostacyclin favors vasodilation thereafter

Biti.n t
During pregnancy, normally, there should be higher  Blood pressure readings
prostacyclin over thromboxane A2. This is reverse in  Creatinine, heaptic aminotransferase, hemogram,

itiII
patients with preeclampsia BUA, LDH, coagulation studies, NST, BPS
Low dose Aspirin  inhibits prostaglandin synthetase so  Evaluation of fetal size and well-being and amnionic
there will ↓ thromboxane A2 and it will favor more the fluid volume
production of prostacyclin = vasodilation o Goal of Management
s  Early identification of worsening preeclampsia
o High dose Calcium
Ig
Role of High dose Calcium:
 Development of a management plan for timely
delivery
Calcium in the periphery causes smooth muscle contraction o Reduced physical activity
in the tunica media = causes vasoconstriction. If we give o Further management depends on:
high dose calcium (>1000 mg) in pregnant patient would  Preeclampsia severity
cause inhibition of parathyroid hormone centrally   Gestational age
causes a decrease in calcium inflow from the bones to the  Condition of the cervix

[Link]
intravascular space. Decrease of calcium concentration
Condition of the cervix could predict whether
intracellularly  there will be no vasoconstriction but
patient can deliver vaginally or by CS if in cases
instead vasodilation
there is a need of termination of pregnancy

4Caexcretionin urine Unlithiasis trisk of

BISHOP scoring is used for checking the condition
Effacement of the cervix  8 and above = normal delivery

ÉÉtÉÉit
#GrindNation Page 10 of 13
cervix
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE) Notable124weeks
Management continued….. <24 weeks – we terminate pregnancy (after maternal stabilization)
Consideration for Delivery  Stabilize the mother first
 Termination of pregnancy - only cure for PE  We have no choice but to terminate pregnancy (anyway, the baby
 Headache, visual disturbances, or epigastric pain are indicative that has no chance of survival)
convulsions may be imminent, and oliguria is another ominous sign
 The prime objectives:
o Forestall convulsions
et
24-<34 weeks – we could do expectant management
 We do observation as long as the mother’s condition is stable
 To improve perinatal outcome without increasing maternal
o Prevent intracranial hemorrhage and serious damage to other morbidity
vital organs  Corticosteroids – to hasten maturity of lungs of baby
o Deliver a healthy newborn 

Fanti
MgSO4 (magnesium sulfate) – enhances CNS maturity
therefore preventing intracranial hemorrhage
(neuroprotection) convulsant mother

**Take note here the Maternal and Fetal Monitoring done while temporizing delivery**

Lecture Discussion: Delivery is an issue of concern

Although termination of pregnancy is the only cure for preeclampsia, delivery
is usually an issue of concern. Why?
**Take note here the drugs given while temporizing delivery**
 If baby is TERM or NEAR TERM with good survival rate in nursery 
delivery (this is an easy decision because you know that the baby
has a good survival rate)
 But if baby is SEVERELY PRETERM  we have the tendency to
TEMPORIZE delivery to push the baby to more maturity (because if
baby is premature, it cannot survive due to premature lungs and
they are at risk of intracranial hemorrhage)
 Now we think of the RISK to the mother since we will TEMPORIZE
the delivery (resolution for this issue is discussed below)

Glucocorticoids
 To enhance fetal lung maturation, glucocorticoids have been
administered to women with severe hypertension who are remote from
term
 Neonatal complications, including respiratory distress, intraventricular
hemorrhage, and death, were decreased significantly when
betamethasone was given
Lecture Discussion: Continuation of delivery issue  Glucocorticoids might aid treatment of the laboratory abnormalities
associated with HELLP syndrome
Preeclamptic patients with severe features in severely preterm AOG  the

methadone 12ms IM 924 x2

safety of the mother and the fetus is important (we ensure the safety of both
and not only 1) Beta
114
Dexamethasone
ansIM a12
Initial management:
 Stabilization of mother’s condition
 Assessment of fetal well-being
 Confirmation of AOG – always use the 1st trimester UTZ (has lower
margin of error)

>34 weeks AOG – we deliver (after maternal stabilization)

 There is already production of surfactants by the type 2
pneumocyte by this time
 In the Philippines, at 34 weeks = 80% neonatal survival rate

#GrindNation Page 11 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Management Eclampsia continued…..

 Schematic clinical management algorithm for suspected severe  Pulmonary edema: a GRAVE prognostic sign
preeclampsia at < 34 weeks  Causes:
1. Aspiration pneumonitis: inhalation of gastric contents
2. Cardiac failure: severe hypertension and vigorous fluid
administration
 Fluids should be restricted to 60 – 125 ml/hr
 Massive cerebral hemorrhage: sudden death
 Blindness due to:
o Retinal detachment
o Occipital lobe infarct or ischemia
 Psychosis: last for 2 weeks and disappears thereafter
o Prognosis is good
o Treatment: Chlorpromazine or Haloperidol

Differential Diagnosis – you rule these out before diagnosis eclampsia

 Epilepsy
 Encephalitis
 Meningitis
 Cerebral tumor
 Hysteria
 Ruptured cerebral aneurysm
Lecture Discussion: Management of Severe Preeclampsia
If <34 weeks AOG – admit the patient Prognosis
 Give MgSO4  Serious
 Give antihypertensive
 Overt threats to maternal life
If with contraindications to conservative management  you terminate the
pregnancy (deliver) Management of Eclampsia
If no contraindications to conservative management  temporize the  Magnesium sulfate is highly effective in preventing convulsions
pregnancy  Tenets
If already at 34 weeks AOG  deliver (baby could possibly survive) 1. Control of convulsions
2. Intermittent administration of an antihypertensive medication
Indications for Delivery in Women <34 Weeks’ Gestation Managed Expectantly 3. Avoidance of diuretics
4. Delivery of the fetus to achieve a remission of preeclampsia

Magnesium Sulfate is used to control convulsion

ECLAMPSIA
 Generalized tonic-clonic convulsions
 Remember that other causes of seizures must be ruled out before saying
that it is eclampsia
 Maternal complications
o Placental abruption
o Neurological deficits
o Aspiration pneumonia
o Pulmonary edema
o Cardiopulmonary arrest RR should be >12
o Acute renal failure UO should be at least 30 cc/hr
o Death
 Facial twitching, rigidity with muscular contraction (15–20 secs → coma
 Fever > 39oC is a GRAVE sign of CNS hemorrhage
 ↑ urine output after delivery: sign of improvement
 Proteinuria / edema disappear within a week
 BP normalizes in 2 weeks postpartum

#GrindNation Page 12 of 13
Strength in knowledge
 PATHOLOGIC OBSTETRICS
Topic: Hypertensive Disorders in Pregnancy
Lecturer: Dr. Estimo (DFE)

Magnesium Sulfate is used to control convulsion Delivery

 Not given to treat hypertension  To avoid maternal risks from cesarean delivery, steps to effect vaginal
 Exerts a specific anticonvulsant action on the cerebral cortex delivery are used initially in women with eclampsia
 Supplementary anticonvulsant medication to control convulsions  These women, who consequently lack normal pregnancy hypervolemia,
o Barbiturate are much less tolerant of even normal blood loss than are normotensive
o Midazolam pregnant women
o Lorazepam  Use of conduction analgesia
 Maintenance MgSO4 therapy is continued for 24 hours after delivery o Hypotension and diminished uterine perfusion


Therapeutic level: 4 – 7 meq/L
48 84 9
Disappearance of patellar reflex: 10 meq/L
 Epidural analgesia
o Not to be considered treatment of preeclampsia


yggy
 Respiratory arrest: 12 meq/L IV or IM meperidine and promethazine
 Antidote (in cases of MgSO4 toxicity):  Local or pudendal analgesia: very safe and effective
o Calcium Gluconate I gm IV 10mL  Conduction (spinal): CI due to hypotension and IV infusion
o
101Discontinue MgSO4 3min  Epidural anethesia: anesthesia of choice
o Tracheal intubation  General anesthesia: transient but severe response to tracheal
o
Pain
Mechanical ventilation intubation intubation
Awake
101CalciumGlygiffIP
Magnesium Sulfate PERSISTENT POSTPARTUM HYPERTENSION
 Anticonvulsant and neuroprotective  Persistence maybe due to:
 Mechanisms of action: 1. Underlying chronic hypertension
1. reduced presynaptic release of the neurotransmitter 2. Mobilization of edema fluid into intravascular compartment
glutamate, 3. Older and obese women
2. blockade of glutamatergic N-methyl-D -aspartate (NMDA) 4. Develop superimposed preeclampsia
receptors,  Complications:
3. potentiation of adenosine action, o Hypertensive encephalopathy
4. improved calcium buffering by mitochondria, o Heart failure
5. blockage of calcium entry via voltage-gated channels o Renal insufficiency
 Uterine Effects o Abruptio placenta
o Did not significantly alter the need for oxytocin stimulation of o Fetal growth restriction
labor, admission-to-delivery intervals, or route of delivery o Fetal death
 Fetal and Neonatal Effects  Recommend therapy if DBP is >/= 100 mmHg
o Beat-to-beat variability  Labetalol and diuretics are effective
o Neonatal depression occurs only if there is severe o Diuretics can now be given since patient has already given birth
hypermagnesemia at delivery (not used when pregnant unless in special cases like pulmonary
o Protective effect of magnesium against the congestion & CHF)
o development of cerebral palsy in very-low -birthweight infants  Fluid therapy
o Normal rate: 60 ml/hr to no more than 125ml/hr
Management of Severe Hypertension o Excessive fluid: pulmonary and cerebral edema
Antihypertensive Drugs  Less tolerant to blood loss due to hemoconcentration
 Hydralazine  or lack of normal pregnancy induced hypervolemia
o Most commonly used
o 5 mg given every 20 min, maximum of 5 doses COUNSELING FOR FUTURE PREGNANCIES
o Satisfactory response: DBP 90 – 100 Future Pregnancies
o Maternal tachycardia and palpitations  Higher risk to develop hypertension in future pregnancies
 Labetalol  Earlier preeclampsia is diagnosed during the index pregnancy, the
o Available in the Philippines but expensive greater the likelihood of recurrence
o 20 mg IV initially followed by 40 mg in 20 minutes and then 80  Preterm delivery and fetal-growth restriction in the first pregnancy
mg every 20 minutes if needed up to a maximum 300-mg dose significantly increased the risk for preeclampsia in the second
o Maternal hypotension and bradycardia pregnancy
 Nifedipine
o 10 mg orally ( repeated in 30 min) LONG TERM CONSEQUENCES
o Sublingually is no longer recommended  Any hypertension during pregnancy is a marker for an increased risk for
morbidity and mortality in later life
 Verapamil
o IV infusion of 5 – 10 mg/hr  Increased for hypertension, ischemic heart disease, stroke, venous
thromboembolism, and all-cause mortality include but are not limited
 Nimodipine
to the metabolic syndrome, diabetes, obesity, dyslipidemia, and
o Continuous infusion or oral
atherosclerosis
 Nitroprusside
o Continuous infusion: 0.25 μg/kg/min Renal  Higher peripheral vascular and renovascular resistance
 Nimodipine & Nitroprusside Sequelae and decreased renal blood flow
o Fetal cyanide toxicity may develop after 4 hours  Long-term persistence of brain white-matter lesions that
 Neurological were incurred during eclamptic convulsions
Diuretics
o
CHFEdema
Before delivery, diuretics are not used to lower blood pressure Sequelae  Multiple seizures had impaired sustained attention
 Had lower vision-related quality of life

#GrindNation Page 13 of 13
Strength in knowledge
Termination