Path: Disorders of Pregnancy

Once the ovum has been fertilized how long does it take for it to divide into a 4 cell stage?

- 2 days *enters the uterus by 3-4 days. Formation of blastocyst occurs by 4-5 day and it attaches between 7-9 days

What is a Hydatidiform Mole?

- Abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts. * remember Hydatidiform moles are important to recognize because they are associated with an increased risk of persistent trophoblastic disease (invasive mole) or choriocarcinoma.

What is the theory regarding the placentas role in preclampsia?

- Abnormality of the maternal fetal vascular interface which will resolve with delivery (abnormal trophoblastic implantation and development of the spiral arteries.)

What is the reason for spontaneous abortions?

- Chromosomal anomalies (trisomy 16) -Hypercoagulable states (antiphospholipid syndrome) -Infection -Exposure to teratogens (especially during first 2 weeks)

How will the patient present?

- High Beta hCG (produced by syncitiotrophoblast) - Abnormal uterine bleeding *remember its a hemorrhagic tumor with early hematogenous spread this tumor is GENETICALLY modified to invade the blood vessels early on

What is an Ectopic pregnancy?

- Implantation of fertilized ovum at a site other than the uterine wall -->usually in the fallopian tube

What will a complete hydatidiform mole look like grossly and on histology?

- Marker Villous Enlargement -Circunferential trophoblastic proliferation -Edema

What is a Partial Hydatidiform Mole?

- Normal ovum fertilized by 2 sperm or 1 sperm that duplicates chromosomes --> 69 chromosomes *Fetal tissues are typically present. increased risk of persistent molar disease, but are not associated with choriocarcinoma.

What is HELLP syndrome?

- Preecalmpsia with thrombotic microangiopathic involving the liver H-->hemolysis EL--> Elevated Liver enzymes LP--> Low Platelets

What is (PRE)ECLAMPSIA?

- Pregnancy induced hypertension, proteinuria and edema that arises usually in the 3rd trimester; seen in approximately 5% of pregnancies

What are the key risk factors for an ectopic pregnancy?

- Scarring (most common) -->PID -IUD -Endometriosis -tumor -post surgery adhesion

What will you see on ultrasound of a patient with a Hydatidiform mole?

- Snowstorm apperance

Rapid Review: Explain the uteroplacental blood circulation from repro 1:

- starts with the maternal blood flow into the intervillous space through decidual spiral arteries (endometrial arteries). - it will circulate around the villi to allow gas and nutrient exchange - - Exchange of oxygen and nutrients take place as the maternal blood flows around terminal villi in the intervillous space. - The in-flowing maternal arterial blood pushes deoxygenated blood into the endometrial and then uterine veins back to the maternal circulation.

Rapid Review: Explain the fetal-placenta blood circulation from repro 1:

- the umbilical ARTERIES to carry deoxygenated and nutrient-depleted fetal blood from the fetus to the villous core fetal vessels. -After the exchange of oxygen and nutrients, the umbilical VEIN carries fresh oxygenated and nutrient-rich blood circulating back to the fetal systemic circulation

How does Abnormal placental vasculature play a pivitol role in the pathophysiology of Preeclampsia?

- there is an abnormal trophoblastic implantation and a failure of physiologic remodeling of the maternal vessels, which is required for adequate perfusion of the placental bed.

A patient who has antiphospholipid antibodies increases the risk of abortion occurring in what trimester?

-1st

A patient who has leiyomiomas increases the risk of abortion occurring in what trimester?

-2nd

If an spontaneous abortion occurs and its due to placental hemorrhage what trimester will it most likely occur in?

-2nd or 3rd

How will a patient classically present?

-2nd trimester (4-5th month) - Vaginal bleeding -Passage of grape like masses * Dx can be made in first trimester by routine sonography and hCG levels

What is a complete abortion?

-All of fetal placental tissue has passed -Os is closed

What will you see clinically in a inevitable abortions?

-Bleeding -OS is open

What will you see clinically in a incomplete abortion?

-Bleeding -All of Fetal-placental tissue is not passed

How will an invasive mole look on histology?

-Chorionic villi is within the myometrium - invades blood vessels and embolize to distant organs, mainly lungs

Which mole will not have nucleated RBCs and has extravillous islands?

-Complete Hydatidiform mole *remember p57 is Not seen as the gene is maternally transcribed but paternally imprinted

On biopsy how will you tell the difference between the two?

-Complete-->p57(-) Partial--> p57 (+) in both cytotrophoblast and villous stroma

If a pregnancy test is positive with bleeding and you do a biopsy of the endometrium. What do you need to see to indicate that it is indeed an ectopic pregnancy?

-Decidual cells -absence of chorionic villi

What are the 3 predispositions leading to preeclampsia?

-Diabetes -Parity -hypertension *remember first pregnancy carries more risk

What is a gestational trophoblastic disease?

-Disease that encompasses a spectrum of tumors and tumor-like conditions characterized by proliferation of placental tissue, either villous or trophoblastic *Remember major disorders of this type are hydatidiform mole (complete and partial), invasive mole, choriocarcinoma.

What is a Complete Hydatidiform Mole?

-EMPTY ovum fertilized by two sperm -->46 chromosomes there will be no fetal tissue.

How will the uterus respond to a hydatidiform mole?

-Expands as if normal pregnancy is there but it will be much much larger -->thats why you see hCG levels much higher than expected for the date of gestation

What is a Choriocarcinoma?

-Germ cell tumor that is malignant and composed of cytotrophoblasts and syncytiotrophoblasts. *remember it will mimic placental tissue with no VILLI

A 34 y.o woman presents with Lower quadrant unilateral abdominal pain. Her last period was 4 weeks ago.But, now shes been bleeding abnormally. You decide to do an emergency surgery because you realize its an ectopic pregnancy. Why does surgery need to happen ASAP?

-If it is an ectopic pregnancy--> Hematosalpinx and rupture can occur Hematosalpinx--> bleeding into the fallopian tube

What will be the morphology of the placenta in a patient with Eclampsia?

-Infarcts -Retroplacental Hemorrhages -Spiral arteries: thrombosis, fibrinoid necrosis and acute atherosis (lipid-laden macrophages)

What type of mole will invade and perforates the uterine wall?

-Invasive mole

In a complete mole why is the ovum absent?

-Maternal DNA is lacking

What are the risks involved in a pregnant patient with hypertension?

-Maternal morbidity and mortality -Stillbirth - preterm -intrauterine growth restriction

What are longer term complications associated with Eclampsia?

-Microalbuminuremia -Hypertension -increase in vascular diseases (Stroke and MI )

Will you see proteinurea in a patient who has Gestational Hypertension?

-NO! *it will return to normal within 3 months after delivery

What is the normal pathogenesis of the placental involving the arteries and circulation?

-Normally an invasion by extravillous fetal trophoblasts destroys the vascular smooth muscle cells --> replaces the maternal endothelial cells with fetal trophoblastic cells. - This converts spiral arteries from small caliber, high resistance vessels to large capacity low-resistance arteries. *This does not happen in preeclampsia-->leaving the placenta ill equipped to meet the increased circulatory demands of late gestation and setting the stage for the development of placental ischemia.

On histology what are key features present in a partial mole?

-Nucleated RBCs -Scalloped outline

What is Eclampsia?

-Preeclampsia with seizures *can also have acute complications like Cerebral edema, ischemia, and hemorrhages--> leading to coma

On histology what will you see that will clue you in that you are looking at choriocarcinoma?

-Proliferative cytotrophoblast -Proliferative syncitiotrophoblast -NO CHORIONIC VILLI *most likely spreads to lungs

How does Diffuse Endothelial Dysfunction and Imbalance of angiogenic and anti-angiogenic factors lead to preeclampsia?

-Remember what JJ said--> Although not formally proven, it is thought that in response to hypoxia, the ischemic placenta releases factors into the maternal circulation that cause an imbalance -this leads to systemic maternal endothelial dysfunction and the clinical symptoms of the disease.

A 32-year-old woman has the sudden onset of lower abdominal pain. Pelvic examination reveals a normal sized uterus. However, there is marked tenderness upon palpation of the left adnexal region. A transvaginal ultrasound shows no intrauterine gestational sac, but there is a 2 cm left adnexal mass. We suspect a ruptured tubal pregnancy. What will be the clinical presentation to aid in diagnosis that this was indeed a tubal rupture?

-Shock -Tachycardia -Peritoneal signs -Severe abdominal pain

If you have bleeding and the Os is closed what kind of abortion is that?

-Threatened abortion

If a patient comes in with tubal hematoma what should be your first thought?

-Tubal pregnancy * Remember this is the most common cause of hematosalpinx (blood-filled fallopian tube) and should always be suspected when a tubal hematoma is present

How will a patient present to you that just had a spontaenous abortion?

-Vaginal Bleeding HEAVYYYY -cramp like pain -passage of fetal tissues

Is rupture of a tubal pregnancy an emergency?

-YES! * Remember patient may rapidly develop hemorrhagic shock with signs of an acute abdomen, and therefore early diagnosis is critical

is there a specific gene product that is absent in a complete hydatidiform mole?

-YES! p57 (p57KIP2 gene product) *this type of mole has increased risk of progressing to choriocarcinoma

In a preclampsic patient will you see proteinurea?

-Yes >300mg/day

When do most spontaneous abortions occur?

-before 20 weeks of gestations ( usually during first trimester)

How should you manage a patient with HELLP syndrome?

-delivery regardless of gestational age *Remember eclampsia, severe preeclampsia with maternal end-organ dysfunction, fetal compromise, or the HELLP syndrome are indications for delivery regardless of gestational age.

What is the step wise process of what can occur if a patient presents with one of the predispositions associated with preeclampsia?

-factor in development is failure of conversion of narrow spiral arteries to low-resistance vascular sinuses in the placenta. -Placental ischemia results in poor fetal growth and liberation of substances which cause vasoconstriction and promote hypertension. -In the kidney, endothelial cells become swollen, with deposition of fibrin in glomeruli, leading to proteinuria. - If untreated severe hypertension and intravascular coagulation occur with development of cerebral ischemia and fits.

What defines a still birth?

-stillbirth has a gestational age of 20 weeks or more - a birth weight of 350 g or more at delivery,

What are the two types of circulation happening during pregnancy?

-the maternal-placental (uteroplacental) blood circulation -the fetal-placental (fetoplacental) blood circulation

what are the three components of the normal placenta?

Maternal part--> Decidua Basalis Fetal Part-->Chorionic plate with chorionic villi Intervillous spaces

Where is p57 normally found?

cytotrophoblast villous stroma