PLACENTAL DISORDERS

Introduction

Diseases of pregnancy and pathologic conditions of the placenta are important causes of fetal intrauterine or perinatal death, congenital malformations, intrauterine growth retardation, maternal death, and morbidity for both mother and child.

Normal placenta anatomy Placenta is derived from both maternal and

fetal tissues. a) The maternal portion of the placenta has

irregular grooves dividing it into cotyledons which are composed of sheets of decidua basalis and remnants of blood vessels.

b) The fetal portion of the placenta is composed of numerous functional units called chorionic villi and comprise the major part of placenta at term.

Chorionic villi In the chorionic villi they

form an extensive capillary system, bringing fetal blood in close proximity to maternal blood.

Chorionic villi composed of delicate mesh of central stroma surrounded by two discrete layers of epithelium i.e, the outer layer consisting of syncytiotrophoblast and the inner layer consisting of cytotrophoblast

Disorders of Early Pregnancy Spontaneous Abortion Ectopic Pregnancy

Disorders of Late Pregnancy Twin Placentas Abnormalities of Placental Implantation Placental Infections Preeclampsia and Eclampsia

Disorders of Early Pregnancy

Spontaneous Abortion Spontaneous abortion, or “miscarriage,” is defined

as pregnancy loss before 20 weeks of gestation. Most of these occur before 12 weeks. 10 to 15% of clinically recognized pregnancies

terminate in spontaneous abortion However, using sensitive HCG assays, it has been

determined that an additional 20% of early pregnancies in otherwise healthy women terminate spontaneously, many without notice.

ETIOLOGY The mechanisms leading to early loss of

pregnancy are unknown. However, multiple fetal and maternal causes of spontaneous abortion have been identified.

Among the most important are the following Fetal chromosomal anomalies, such as

aneuploidy, polyploidy, and translocations, are present in approximately 50% of early abortuses.

Maternal endocrine factors, including luteal-phase defect, poorly controlled diabetes, and other uncorrected endocrine disorders

Physical defects of the uterus, such as submucosal leiomyomas, uterine polyps, or uterine malformations, may prevent or disrupt implantation

Systemic disorders affecting the maternal vasculature, such as antiphospholipid antibody syndrome, coagulopathies, and hypertension

Infections with protozoa (Toxoplasma), bacteria (Mycoplasma, Listeria), or a number of viruses. Ascending infection is particularly common in second trimester losses.

Ectopic Pregnancy Ectopic pregnancy refers to implantation of the

fetus in a site other than the normal intrauterine location

The most common site is the extrauterine fallopian tube (approximately 90% of cases).

Other sites include the ovary, the abdominal cavity, and the intrauterine portion of the fallopian tube (cornual pregnancy)

Ectopic pregnancies account for 2% of confirmed pregnancies

RISK FACTORS OF ECTOPIC PREGNANCY

Pelvic inflammatory disease resulting in intralumenal fallopian tube scarring (chronic salpingitis)

Peritubal scarring and adhesions, which may be caused by appendicitis, endometriosis, and previous surgery

Intrauterine contraceptive device(associated with twofold increase of ectopic pregnancy)

MORPHOLOGY In each abnormal location, the fertilized

ovum develops as usual, forming placental tissue, amniotic sac, and fetus. The host implantation site may also develop decidual changes.

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

Consequences of Ectopic Pregnancy

With time the growth of the gestational sac distends the fallopian tube, causing thinning of the wall and rupture. The rupture frequently results in massive intraperitoneal hemorrhage, which sometimes is fatal.

Less commonly the tubal pregnancy may undergo spontaneous regression and resorption, or be extruded through the fimbriated end of the tube into the abdominal cavity (tubal abortion).

Clinical Features Rupture of a tubal pregnancy is a medical

emergency. The clinical course of ectopic tubal pregnancy is

characterized by the onset of moderate to severe abdominal pain

and vaginal bleeding 6 to 8 weeks after last

menstrual period, correlating with distention and then rupture of the fallopian tube, causing hemorrhagic shock with signs of an acute abdomen, and therefore early diagnosis is critical

Diagnosis of ectopic pregnancy

Diagnosis is based on Determination of chorionic gonadotropin

titers, Pelvic sonography, Endometrial biopsy (which shows decidua

without chorionic villi or implantation site) and/or

Laparoscopy

Disorders of Late Pregnancy

Twin Placentas Twin pregnancies arise from fertilization of

two ova (dizygotic) or from division of one fertilized ovum (monozygotic).

There are three basic types of twin placentasa) diamnionic dichorionic (which may be fused),b) diamnionic monochorionic, and c) monoamnionic monochorionic.

Monochorionic placentas imply monozygotic (identical) twinsDichorionic placentation may occur with either monozygotic or dizygotic twins

Complication Complication of monochorionic twin pregnancy is

twin-twin transfusion syndrome. Monochorionic twin placentas have vascular

anastomoses that connect the circulations of the twins, and in some cases these connections include one or more arteriovenous shunts

If these shunts preferentially increase blood flow to

one twin at the expense of the second, one twin will be underperfused, while the second will be fluid overloaded.

It is this phenomenon that constitutes the twin-twin transfusion syndrome, which if severe may result in the death of one or both fetuses.

Abnormalities of Placental ImplantationPlacenta previa Condition in which the placenta implants

in the lower uterine segment or cervix Often leading to serious third trimester

bleeding. A complete placenta previa covers the

internal cervical os and thus requires delivery via cesarean section to avert placental rupture and fatal maternal hemorrhage during vaginal delivery

Placenta completely covers the top of cervix

Placenta partially covers the top of the cervix

Placenta accreta occurs when all or part of the placenta attaches abnormally to the myometrium (the muscular layer of the uterine wall). 

Caused by partial or complete absence of the decidua, such that the placental villous tissue adheres directly to the myometrium, which leads to a failure of placental separation at birth.

It is an important cause of severe, potentially life threatening postpartum bleeding.

Common predisposing factors are Placenta previa (in up to 60% of cases) and History of previous cesarean section

Placenta accreta

Three grades of abnormal placental attachment are defined according to the depth of invasion:

a) Accreta – chorionic villi attach strongly to the myometrium (but does not penetrate it), rather than being restricted within the decidua basalis

b) Increta – chorionic villi invade into the myometrium

c) Percreta – chorionic villi invade through the myometrium (penetrates the entire myometrium to the uterine serosa)

Placental Infections Infections in the placenta develop by two pathways: (1)Ascending infection through the birth canal and (2)Hematogenous (transplacental) infection Ascending infections are by far the most common

and are virtually always bacterial Localized infection of the membranes produces

premature rupture of membranes and preterm delivery.

The amniotic fluid may be cloudy with purulent exudate, and histologically the chorionamnion contains an infiltrate of neutrophils accompanied by edema and congestion of the vessels.

The infection frequently elicits a fetal response consisting of a “vasculitis” of the umbilical and fetal chorionic plate vessels.

Uncommonly, bacterial infections may result from hematogenous spread to the placenta, leading to acute villitis

Several hematogenous infections, classically components of the TORCH group (toxoplasmosis and others [syphilis, tuberculosis, listeriosis], rubella, cytomegalovirus, herpes simplex), can affect the placenta.

Preeclampsia and Eclampsia

Preeclampsia is a systemic syndrome characterized by widespread maternal endothelial dysfunction that presents during pregnancy with hypertension, edema, and proteinuria

Preeclampsia should be distinguished from gestational hypertension that can develop in pregnancy without proteinuria.

It occurs in about 3% to 5% of pregnant women, usually in the last trimester and more commonly in primiparas (women pregnant for the first time).

Onset of seizures (convulsions) or coma in association with syndrome of pre-eclampsia is called Eclampsia.

Pathogenesis Although the exact mechanisms leading to

development of preeclampsia are still being investigated, it is clear that the placenta plays a central role in the pathogenesis of the syndrome, since the symptoms disappear rapidly after delivery of the placenta.

The critical abnormalities in preeclampsia are 1) Diffuse endothelial dysfunction, 2) Vasoconstriction (leading to hypertension), and 3) Increased vascular permeability (resulting in

proteinuria and edema)

Pathogenesis (Cont.)

The principal pathophysiologic aberrations appear to be the following:

Abnormal placental vasculature Endothelial dysfunction and imbalance of

angiogenic and antiangiogenic factors Coagulation abnormalities

Abnormal placental vasculature

In normal pregnancy, the musculoelastic walls of the spiral arteries are invaded by trophoblasts, permitting them to dilate into wide vascular sinusoids. In preeclampsia and eclampsia, this vascular remodeling is impaired, the musculoelastic walls are retained and the channels remain narrow. Decreased uteroplacental blood flow appears to result in placental hypoxia, placental dysfunction, and a shift to a systemic antiangiogenic state.

Endothelial dysfunction and imbalance of angiogenic and antiangiogenic factors

Balance between pro-angiogenic (VEGF and TGFβ) and anti-angiogenic factors (soluble soluble fms-like tyrosine kinase sFlt and soluble endoglin) is essential for the normal function of placenta.

There imbalance are hypothesized to result in endothelial cell dysfunction, vascular hyperreactivity, and end-organ microangiopathy

When placenta-derived anti-angiogenic factors i.e, sFlt and endoglin are overexpressed together, rats develop nephrotic-range proteinuria, severe hypertension, and fetal growth restriction, the hallmarks of severe preeclampsia, as well as features of the HELLP syndrome, including elevated liver enzymes, decreased platelet counts, and hemolysis

Thus, it seems that sFlt1 and soluble endoglin are key mediators that link the placenta to the characteristic maternal endothelial dysfunction of preeclampsia.

Coagulation abnormalities Preeclampsia is associated with

hypercoagulability which is likely related to the reduced endothelial production of PGI2, a potent antithrombotic factor, and increased release of procoagulant factors

This hypercoagulable state may lead to the formation of thrombi in arterioles and capillaries throughout the body, but particularly in the liver, kidneys, brain, and pituitary.

MORPHOLOGY Placental abnormalities include:a) Infarcts, which can be a feature of normal pregnancy,

but are much more numerous with severe preeclampsia or eclampsia

b) Retroplacental hemorrhagesc) Premature maturation of placental villi associated with

villous edema, hypovascularity, and increased production of syncytial epithelial knots

d) Fibrinoid necrosis and focal accumulation of lipid containing macrophages (acute atherosis) of decidual vessels

liver lesions when present, take the form of irregular, focal, subcapsular, and intraparenchymal hemorrhages

fibrin thrombi in the portal capillaries foci of hemorrhagic necrosis kidney lesions are variable. Glomeruli show marked swelling of endothelial cells,

amorphous dense deposits on the endothelial side of the basement membrane, and mesangial cell hyperplasia.

• bilateral renal cortical necrosis (widespread and severe cases)

Brain, heart and the anterior pituitary may have Foci of hemorrhage along with small-vessel thromboses

Clinical Features Preeclampsia most commonly starts after 34 weeks of

gestation but begins earlier in women with hydatidiform mole or preexisting kidney disease, hypertension, or coagulopathies.

The onset is typically insidious, characterized by hypertension and edema, with proteinuria following within several days. Headaches and visual disturbances are serious events and are indicative of severe preeclampsia, often requiring delivery.

Eclampsia is heralded by central nervous system involvement, including convulsions and eventual coma.

MANAGEMENT For term pregnancies: delivery is the treatment

of choice regardless of disease severity. In preterm pregnancies, where delivery may

not be in the best interest of the fetus, patients with mild disease can be managed expectantly by closely monitoring the mother and fetus.

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

COMPLICATIONS AND CONSEQUENCES Hypercoagulability, Acute renal failure, and Pulmonary edema HELLP syndrome Although in most instances preeclampsia has no

lasting sequelae, recent studies indicate that about 20% of affected women develop hypertension and microalbuminuria within 7 years of a pregnancy complicated by preeclampsia.

There is also a twofold increase in the long term risk of vascular diseases of the heart and the brain.

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