Obstetric Pathology 2

Question 1

Define pre-eclampsia.

Answer 1

Complication of pregnancy, a systemic syndrome of maternal endothelial dysfunction causing hypertension, proteinuria, and edema.

Question 2

How common is pre-eclampsia?

Answer 2

It is increasingly common, occurring
in 7.5% of pregnancies, usually in the
third trimester.

Question 3

What are risk factors for pre-eclampsia?

Answer 3

First pregnancy
Age less than 20 or over 40
Obesity
Diabetes mellitus
Hypertension
New paternity
Previous pre-eclampsia
Multiple pregnancies
Long interval between pregnancies

Question 4

Pathogenesis of pre-eclampsia

Answer 4

Normally, trophoblast cells invade
 myometrial spiral arteries going to the
 placenta, destroy the smooth muscle
 cells in their walls and convert them
 from small caliber resistance vessels
 to large caliber capacitance vessels
 that accommodate vastly increased
 blood flow later in gestation.
Pre-eclamptic trophoblast fail to thus
 convert spiral arteries, resulting in
 placental ischemia

Question 5

Ischemic placenta releases what anti-angiogenic substances? What does this do?

Answer 5

(1) soluble fms-like tyrosine kinase 1
     (sFlt-1), a truncated form of VEGF
     receptor that acts as a decoy
(2) soluble endoglin, a form of TGF-beta
     receptor that acts as a decoy
blocks VEGF and TGF mediated
 production of nitric oxide and prosta-
 cyclin, causing maternal hypertension,
 proteinuria and edema.

Question 6

Ischemic placenta also releases proinflammatory cytokines like ____.

Answer 6

TNF

Question 7

Pre-ecmalpsia is a ____ state partly due to blockage of prostacyclin production.

Answer 7

procoag

Question 8

What are some of the deleterious effects of pre-eclampsia on placenta, baby, and momma?

Answer 8

including fetal intrauterine growth
restriction (IUGR), maternal disseminated intravascular coagulation, maternal HELLP syndrome (Hemolysis, Elevated Liver enzymes and Low Platelets) and eclampsia (cerebral edema and seizures).

Question 9

T or F. Pre-eclampsia and eclampsia are associated with visible changes in
placental arteries very similar to atherosclerosis (a universal disease
of arterial endothelial injury in all permanent organs).

Answer 9

T

Question 10

Histological changes of uterine blood vessels in eclampsia?

Answer 10

acute atherosis with fibrinoid necrosis/ leakage of plasma, subendothelial macrophages

Question 11

What is the effect of ischemia on chorionic villi?

Answer 11

The initial effect of ischemia on the development of chorionic villi is accelerated
maturation that makes them more efficient at gas exchange, nutrient import
and waste export, but when ischemia becomes more severe, it results in
villous hypoplasia.

Question 12

How does necrosis of villi result from pre-eclampsia?

Answer 12

Sluggish blood flow in the intervillous space
and the procoagulant state of pre-eclampsia can lead to fibrin clot formation in the intervillous space, which can lead to necrosis of villi, “choked off” by the clot around them.

Question 13

How is diagnosis of pre-eclampsia made? What is the treatment and prognosis?

Answer 13

Diagnosis: new onset of hypertension
& proteinuria after 20 weeks gestation

Treatment depends on whether it is
 mild or severe.  Mild: “expectant
 management” (including steroids to
 accelerate fetal lung development)
   Severe: delivery

Prognosis: wide spectrum

Question 14

What is HELLP syndrome?

Answer 14

(hemolysis, elevated
liver enzymes and low platelets)
= a complication of pre-eclampsia in
4-12% of patients with pre-eclampsia

Question 15

Pathogenesis of HELLP syndrome

Answer 15

activation of platelets
 and clotting factors, creating fibrin
 red cell shredders in capillaries that
 causes hemolysis, platelet aggregation
 lowering the count, and thrombi in
 liver sinusoids that injure hepatocytes,
 who release their enzymes

Question 16

What happens to the liver in HELLP syndrome

Answer 16

Liver injury can progress to necrosis,

hemorrhage, even liver rupture.

Question 17

Complications of HELLP syndrome

Answer 17

20% of patients with HELLP syndrome get disseminated intravascular coagulation;
some get hepato- renal failure,some pulmonary edema and acute respiratory distress
syndrome (ARDS),and 1% die of it.

Question 18

Causes of placental ischemia and infarction

Answer 18

Pre-eclampsia is the overwhelmingly
 most common cause, but hyper-
 coagulable states, autoimmune
 vasculitis and smoking are also
 causes of it.

Question 19

The fetus can tolerate infarction of _____ of the placenta, but extensive infarction causes IUGR, neurological injury, and fetal demise.

Answer 19

more than 50%

Question 20

What does heavy prenatal drinking do to childhood brain development?

Answer 20

disrupts proper brain development in children and adolescents years after they were exposed to alcohol in the womb.decreased brain plasticity – the brain’s ability to grow and remodel itself based on experience with the outside world. Such adaptation continues throughout one’s life and is crucial to learning new skills and adapting to the environment.

Question 21

Describe invasive mole and choriocarcinoma

Answer 21

there is a spectrum from non-invasive moles through invasive moles to choriocarcinomas.
7% of partial moles persist after
 therapy and none become carcinoma.
20% of complete moles persist after
 initial therapy and 2% become
 choriocarcinomas.
Invasive moles look like well
 differentiated choriocarcinomas, but
 do not metastasize

Question 22

How common is choriocarcinoma?

Answer 22

rare- 1/30,000 pregnancies

Question 23

Spread of choriocarcinoma

Answer 23

Spreads hematogenously

(like a sarcoma), so to lungs first

Question 24

Most common first symptom of choriocarcinoma

Answer 24

uterine bleeding

Question 25

What is the treatment and prognosis of choriocarcinoma?

Answer 25

hysterectomy and chemo; 70% survival of mets

Question 26

What is oligohydramnios?

Answer 26

Deficiency of amniotic fluid

Causes a sequence of compressive
 injuries to the fetus, but also
 pulmonary hypoplasia because the
 fetus needs to “breathe” for normal
 lung development, and absence of
 fetal “urine” in amniotic fluid due to
 fetal renal disease causes pulmonary
 hypoplasia incompatible with life
 after birth.

Question 27

What happens to the hands, feet, and face with oligohydramnios

Answer 27

Potters facies: flattened face, nose, and ears

Severe deformation of hands and feet- clubfeet

Question 28

What are amniotic bands?

Answer 28

mechanical fibrotic lesions

causing limb strictures or amputations

Question 29

Umbilical cord true knots occur
 in \_\_\_ of pregnancies and can
 cause fetal demise, especially
 in the second trimester when
 fetal movement can pull on it.

Answer 29

1%

Question 30

What is the significance of hyper- and hypo-coiling of umbilical cord?

Answer 30

poor OB outcomes

Question 31

What is placental abruption?

Answer 31

bleeding at the decidual-placental interface
causing placental detachment before delivery of the fetus.
The detachment can be partial
or total.
It complicates 1% of pregnancies
and the incidence is increasing.

Question 32

__% of placental abruptions
cause fetal demise and abruption
causes __% of perinatal mortality.

Answer 32

10;8

Question 33

What is the immediate cause of placental abruption?

Answer 33

decidual blood vessels

Question 34

How are placental abruptions related to hematomas?

Answer 34

This results in a retroplacental
hematoma in 2/3 of cases, but
1/3 of hematomas are without
associated abruption

Question 35

What is the risk of PE in pregnancy?

Answer 35

The risk is increased up to 50-fold
with pregnancy and up to 1 in 500
 pregnancies is complicated by
 pulmonary thromboembolism.
The risk is greater during & after 
 delivery than before because that
 releases compression of the IVC.
The vast majority come from deep
 vein thrombosis in left leg.

Question 36

What is amniotic fluid embolism?

Answer 36

Life-threatening obstetric
emergency due to acute cardio-
pulmonary failure from pulmonary
vasospasm, hypertension and right
heart failure triggering pulmonary
diffuse alveolar damage, sometimes
with a second phase of DIC and
hemorrhage

Question 37

How common is amniotic fluid emoblism?

Answer 37

Rare, but true incidence hard to 
 pin down (between 1 in 8,000 and
 1 in 30,000 deliveries

Question 38

What causes AFE?

Answer 38

fetal and amniotic elements entering maternal veins as decidua detaches and embolizing to lungs, which react with vasospasm,

Question 39

Complications of AFE?

Answer 39

Commonly fatal to the mother, but
true fatality rate hard to pin down
(between 25% and 80%)

Thought to account for 5-10% of
maternal deaths in the US.

Less commonly fatal to the baby,
but about 20% die after their
mothers develop the syndrome.

Question 40

What is peripartum cardiomyopathy?

Answer 40

A myocarditis
(possibly immune mediated)
which resolves spontaneously (in 1/3) or
leads to dilated cardiomyopathy (in 2/3)

Question 41

Epidemiology of peripartum cardiomyopathy

Answer 41

Rare (1:1,300 to 1:15,000 pregnancies),

Most common in multiparous African-Americans

Question 42

How do you diagnose and treat peripartum cardiomyopathy?

Answer 42

dilated cardiomyopathy
without another cause
3 months before or after delivery

Treatment
(if it fails to resolve spontaneously):
heart transplantation

Question 43

DDx for acute onset dyspnea during labor and delivery

Answer 43

Pulmonary thromboembolism
Pulmonary edema (if pre-eclamptic)
Peripartum cardiomyopathy
Amniotic fluid embolism
Anxiety
Magnesium sulfate toxicity
 (if on magnesium sulfate for
  eclampsia)

Question 44

Maternal deaths in US

Answer 44

The rate of maternal death in the US
 has been increasing for over 20 years.
The mortality rate in postpartum
 hospitalizations increased 66%
 between 1999 and 2009.
The maternal death rate is 3X higher
 for black women.
The five leading causes of maternal
 death are thromboembolism (20%),
 hemorrhage (17%), pre-eclampsia (16%)
 infection (13%) & cardiomyopathy (8%).