Pathology of pregnancy

1. Placental Inflammation + Infections

Two pathways

A) Ascending infection through birth canal

• Most common.
• Usually bacterial (vaginal flora) + Candida albicans.
• Causes acute chorioamnionitis; extends beyond membrane → acute vasculitis of umbilical cord (funisitis).
• Consequences: premature birth + premature rupture of membranes.

B) Hematogenous (transplacental) infection

• Very rare.
• Syphilis, TBC, listeriosis, toxoplasmosis, viruses (rubella, CMV, HSV) → placental villitis.
• Fetal involvement → TORCH complex (Toxoplasma, Other [syphilis], Rubella, CMV, HSV).

2. Ectopic Pregnancy

Definition

• Implantation of fertilized ovum outside the uterine cavity.
• > 90 % in fallopian tubes; other sites: ovary, abdominal cavity, cervix.

Special locations

• Ovarian pregnancy — ovum fertilized within its follicle just at rupture.
• Abdominal pregnancy — fertilized egg drops out of fimbriated end → implants in peritoneum.

Pathogenesis

• Anything that retards passage of ovum through the fallopian tube:
  • Inflammation (chronic salpingitis — #1)
  • Intrauterine tumors
  • Endometriosis
  • Prior tubal surgery, IUD, smoking

Clinical features

• Until rupture: indistinguishable from normal pregnancy (↑ hCG, endometrial changes).
• Rupture → abdominal bleeding + hypovolemic shock → surgical emergency.
• β-hCG lower than expected for gestational age (relative).

3. Gestational Trophoblastic Disease (GTD)

• Group of pregnancy-related disorders arising from trophoblasts.

• All produce ↑ hCG — detectable in blood at unusually high titers vs normal pregnancy.

• Spectrum (increasing aggressiveness + hCG):

  Hydatidiform mole → Invasive mole → Choriocarcinoma

A) Hydatidiform Mole

• Voluminous mass of swollen, dilated chorionic villi.
• Villi covered by varying amounts of atypical chorionic epithelium.
• Most common: < 20 yr and > 40 yr.
• Two patterns from abnormal fertilization:

Feature	Complete mole	Partial mole
Fertilization	Empty egg • 2 sperm (or 1 sperm duplicated)	Normal egg • 2 sperm
Karyotype	Diploid 46XX (or 46XY)	Triploid 69XXY
Embryo	No embryogenesis — no fetal parts	Early embryo — fetal parts present
Villi	ALL villi abnormal	Some normal villi
hCG	Very high	Mildly elevated
Malignancy risk	2.5 % → choriocarcinoma	Rare

B) Invasive Mole

• Complete moles with local invasion of uterine wall.
• No aggressive metastatic potential (unlike choriocarcinoma).
• May rupture → hemorrhage.
• Difficult to fully remove → persistently elevated hCG.
• Tx: chemotherapy.

C) Choriocarcinoma

• Very aggressive malignant trophoblastic tumor from gestational chorionic epithelium or totipotent gonadal cells.
• Develops after pregnancy if remaining cells become cancerous.
• Antecedent: complete hydatidiform mole (50 %), pregnancy, abortion, ectopic.
• Risk: < 20 and > 40 yr.
• Clinical: bloody/brownish discharge + rising hCG titer + absence of expected uterine enlargement.
• Already metastasized by diagnosis → lungs, vagina, brain, liver, kidneys (hematogenous).
• Tx: chemotherapy curative in nearly 100 % of gestational cases.
• Worse prognosis if arising in gonads (non-gestational).

4. Preeclampsia / Eclampsia (Toxemia of Pregnancy)

Definitions

• Preeclampsia: hypertension + proteinuria + edema during 3rd trimester.
• Eclampsia: preeclampsia + convulsive seizures ± impaired renal function.
• HELLP syndrome: Hemolysis, Elevated Liver enzymes, Low Platelets.

Epidemiology

• Especially first pregnancy in women > 35 yr (also < 20, multiple gestation, diabetes, HTN, obesity).

Pathogenesis

• Normally in 3rd trimester: musculoskeletal wall of spiral arteries → replaced by fibrous material → dilation → ↑ placental perfusion.
• In preeclampsia/eclampsia: this replacement does NOT occur → spiral arteries remain narrow → abnormal placentation.

Consequences

• Placental hypoperfusion → infarction.
• ↓ Trophoblast vasodilators (NO, PGI₂) → systemic hypertension.
• Ischemic placenta releases thromboplastic substances (tissue factor) → DIC.
• Glomerular endotheliosis → proteinuria.

💡 High-yield: Placental infection: ascending (#1, bacterial → chorioamnionitis) vs hematogenous (rare, TORCH). Ectopic pregnancy = >90 % tubal; #1 cause = chronic salpingitis; rupture → shock. GTD: Complete mole = empty egg + 2 sperm, 46XX diploid, no fetus, all villi abnormal, very high hCG; Partial mole = normal egg + 2 sperm, 69XXY triploid, fetal parts. Choriocarcinoma: aggressive, hematogenous mets (lungs, vagina, brain, liver), ↑↑ hCG, ~100 % cured by chemo (gestational). Preeclampsia = HTN + proteinuria + edema (3rd trimester); fail to remodel spiral arteries → placental hypoperfusion → ↓ NO/PGI₂ → HTN; → DIC. Eclampsia = + seizures.