Gestosis and Trophoblastic Disease

Pathogenesis and Multiorgan Failure

The pathogenesis of gestosis is complex. The triggering event is vascular endothelial injury combined with systemic hypertension. Endothelial dysfunction triggers prolonged vasospasm, which leads to ischemia of the myocardium, liver, and kidneys.

Placental ischemia is of paramount importance. Exposed to severe hypoxia, the placenta releases thromboplastic substances into the maternal circulation. The combination of these circulating factors and primary endothelial injury initiates disseminated intravascular coagulation (DIC). Multiple microthrombi form within the capillary bed, further exacerbating dystrophic changes in vital organs. Underlying maternal genetic mutations in coagulation factors or platelet abnormalities predispose the patient to severe DIC.

Concurrently, fluid retention and the transudation of plasma into surrounding tissues lead to hypovolemia and edema. The culmination of this pathological cascade is multiorgan failure.

Clinical Presentation

The condition classically progresses through several sequential stages:

1. Basic gestosis: Presents with the classic triad of progressive edema, elevated blood pressure, and proteinuria.
2. Preeclampsia: Patient status deteriorates; the classic triad is accompanied by symptoms of impaired cerebral circulation, such as severe headache and visual disturbances.
3. Eclampsia: A critical state with extremely high mortality defined by the onset of tonic-clonic seizures. Seizures can be triggered by minimal external stimuli or begin entirely spontaneously (derived from the Greek term for "sudden flash").

Modern clinical presentations of gestosis exhibit marked polymorphism. The classic triad is now observed in only 15% of cases, with atypical and monosymptomatic forms predominating in obstetric practice, necessitating heightened diagnostic vigilance. Other severe, high-mortality complications include acute fatty liver of pregnancy and HELLP syndrome.

Pathology of Target Organs

Morphological changes in gestosis reflect widespread ischemia and intravascular thrombosis.

• Liver: Grossly, subcapsular hematomas may form, with rupture risking massive intraperitoneal hemorrhage. Pale-yellow necrosis foci (single or confluent) and hemorrhages are visible in the parenchyma. Histology reveals fibrin thrombi within portal tract vessels.
• Kidneys: Capillary endothelial swelling occurs in the renal glomeruli, with fibrin deposits along the basement membrane. Immune complex mesangial glomerulonephritis may be observed. Severe cases progress to nephrotic necrosis and acute kidney injury.
• Brain: Microscopic and macroscopic foci of hemorrhage and thrombosis of small vessels are identified. Massive cerebral hemorrhages (especially in the basal ganglia) are a leading cause of death.
• Placenta and Uterus: Spiral arteries of the placental bed fail to undergo normal physiological transformation, developing atherosis (accumulation of a wide layer of fibrinoid containing large foam cells, clearly visible on hematoxylin and eosin staining). Placental ischemia leads to trophoblast basement membrane thickening, cytotrophoblast hyperplasia, infarctions, and an excess of syncytial knots. Premature placental abruption may occur.

The fetus suffers severely from hypoxia and intrauterine growth restriction due to placental damage, resulting in preterm birth. Intrauterine fetal demise is frequently documented in eclampsia.

Gestational Trophoblastic Disease

Gestational trophoblastic disease comprises a group of disorders originating from placental tissue. While rare overall, the risk is significantly higher in pregnant individuals younger than 16 and older than 35. This group includes hydatidiform mole (1 in 1,000 pregnancies), invasive mole, choriocarcinoma (2 in 100,000 pregnancies), and placental site trophoblastic tumor.

Hydatidiform mole grossly presents as an enlarged uterus where chorionic villi are transformed into clear fluid-filled vesicles resembling bunches of grapes. These structures may lie free in the uterine cavity and pass via the vagina. Histology (H&E stain) demonstrates marked edema of variably sized villi, forming central fluid-filled cavities known as "cisterns".

Two variants exist:

• Complete hydatidiform mole: Displays a diploid karyotype of 46,XX derived exclusively from paternal chromosomes. It arises either from the fertilization of an "empty" (anuclear) oocyte by a 23,X sperm followed by chromosomal duplication, or via dispermic fertilization. The entire placental tissue is involved, and no fetus is present.
• Partial hydatidiform mole: Characterized by a triploid karyotype resulting from an extra set of paternal chromosomes. Edematous villi are distributed focally among normal placental tissue. A fetus is initially formed but inevitably perishes in early gestation.