Obstetric Pathology 2 Flashcards
Define pre-eclampsia.
Complication of pregnancy, a systemic syndrome of maternal endothelial dysfunction causing hypertension, proteinuria, and edema.
How common is pre-eclampsia?
It is increasingly common, occurring
in 7.5% of pregnancies, usually in the
third trimester.
What are risk factors for pre-eclampsia?
First pregnancy Age less than 20 or over 40 Obesity Diabetes mellitus Hypertension New paternity Previous pre-eclampsia Multiple pregnancies Long interval between pregnancies
Pathogenesis of pre-eclampsia
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
Ischemic placenta releases what anti-angiogenic substances? What does this do?
(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.Ischemic placenta also releases proinflammatory cytokines like ____.
TNF
Pre-ecmalpsia is a ____ state partly due to blockage of prostacyclin production.
procoag
What are some of the deleterious effects of pre-eclampsia on placenta, baby, and momma?
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).
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).
T
Histological changes of uterine blood vessels in eclampsia?
acute atherosis with fibrinoid necrosis/ leakage of plasma, subendothelial macrophages
What is the effect of ischemia on chorionic villi?
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.
How does necrosis of villi result from pre-eclampsia?
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.
How is diagnosis of pre-eclampsia made? What is the treatment and prognosis?
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
What is HELLP syndrome?
(hemolysis, elevated
liver enzymes and low platelets)
= a complication of pre-eclampsia in
4-12% of patients with pre-eclampsia
Pathogenesis of HELLP syndrome
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
What happens to the liver in HELLP syndrome
Liver injury can progress to necrosis,
hemorrhage, even liver rupture.
Complications of HELLP syndrome
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.
Causes of placental ischemia and infarction
Pre-eclampsia is the overwhelmingly most common cause, but hyper- coagulable states, autoimmune vasculitis and smoking are also causes of it.
The fetus can tolerate infarction of _____ of the placenta, but extensive infarction causes IUGR, neurological injury, and fetal demise.
more than 50%
What does heavy prenatal drinking do to childhood brain development?
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.
Describe invasive mole and choriocarcinoma
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
How common is choriocarcinoma?
rare- 1/30,000 pregnancies
Spread of choriocarcinoma
Spreads hematogenously
(like a sarcoma), so to lungs first
Most common first symptom of choriocarcinoma
uterine bleeding
What is the treatment and prognosis of choriocarcinoma?
hysterectomy and chemo; 70% survival of mets
What is oligohydramnios?
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.
What happens to the hands, feet, and face with oligohydramnios
Potters facies: flattened face, nose, and ears
Severe deformation of hands and feet- clubfeet
What are amniotic bands?
mechanical fibrotic lesions
causing limb strictures or amputations
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.
1%
What is the significance of hyper- and hypo-coiling of umbilical cord?
poor OB outcomes
What is placental abruption?
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.
__% of placental abruptions
cause fetal demise and abruption
causes __% of perinatal mortality.
10;8
What is the immediate cause of placental abruption?
decidual blood vessels
How are placental abruptions related to hematomas?
This results in a retroplacental
hematoma in 2/3 of cases, but
1/3 of hematomas are without
associated abruption
What is the risk of PE in pregnancy?
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.
What is amniotic fluid embolism?
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
How common is amniotic fluid emoblism?
Rare, but true incidence hard to pin down (between 1 in 8,000 and 1 in 30,000 deliveries
What causes AFE?
fetal and amniotic elements entering maternal veins as decidua detaches and embolizing to lungs, which react with vasospasm,
Complications of AFE?
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.
What is peripartum cardiomyopathy?
A myocarditis
(possibly immune mediated)
which resolves spontaneously (in 1/3) or
leads to dilated cardiomyopathy (in 2/3)
Epidemiology of peripartum cardiomyopathy
Rare (1:1,300 to 1:15,000 pregnancies),
Most common in multiparous African-Americans
How do you diagnose and treat peripartum cardiomyopathy?
dilated cardiomyopathy
without another cause
3 months before or after delivery
Treatment
(if it fails to resolve spontaneously):
heart transplantation
DDx for acute onset dyspnea during labor and delivery
Pulmonary thromboembolism Pulmonary edema (if pre-eclamptic) Peripartum cardiomyopathy Amniotic fluid embolism Anxiety Magnesium sulfate toxicity (if on magnesium sulfate for eclampsia)
Maternal deaths in US
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%).
