Preeclampsia and Eclampsia (Lecture 2)

Slide 1 · Preeclampsia and Eclampsia

Placental disease and maternal microvascular injury

Clinicopathologic mechanisms · placental morphology · complications

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning goals

Explain the two linked stages: Abnormal placentation and maternal endothelial injury.

Recognize placental maternal vascular malperfusion lesions and their pathogenesis.

Connect systemic endothelial dysfunction with renal, neurologic, hepatic and hematologic effects.

Distinguish preeclampsia, eclampsia and HELLP syndrome and interpret clinical scenarios.

Slide 3 · A systemic disease with a placental origin

Placenta

Inadequate physiologic spiral-artery remodeling

Relative uteroplacental underperfusion

Maternal vessels

Circulating antiangiogenic influence

Diffuse endothelial dysfunction

Target organs

Hypertension and protein leakage

Microthrombi and organ dysfunction

Slide 4 · Clinical syndrome: Core boundaries

Typically recognized after 20 weeks of gestation, most often in the last trimester.

New hypertension occurs with proteinuria or another maternal organ/uteroplacental manifestation.

Eclampsia denotes convulsions attributable to the hypertensive pregnancy disorder.

Severe disease threatens both maternal organ function and placental–fetal perfusion.

Slide 5 · Hypertensive disorders: Pattern recognition

Condition

Defining clinical pattern

Gestational hypertension

New hypertension after 20 weeks without additional preeclampsia findings.

Preeclampsia

New hypertension with proteinuria and/or organ or uteroplacental dysfunction.

Preeclampsia with severe features

Preeclampsia with specified severe BP or end-organ findings (ACOG).

Eclampsia

New-onset convulsions not explained by another cause in this setting.

HELLP spectrum

Hemolysis, elevated liver enzymes, low platelets; serious preeclampsia manifestation.

Slide 6 · Timing: Early placental insult, later maternal disease

Early implantation

Extravillous trophoblast invasion and vessel remodeling

Placental adaptation

Low-resistance uteroplacental blood flow must increase with gestation

Late maternal syndrome

Defective perfusion → placenta-derived mediators → systemic manifestations

Slide 7 · Risk context emphasized

Occurs in approximately 3–5% of pregnancies account.

More often reported in first pregnancies (primiparity).

Underlying hypertension, kidney disease or coagulopathy may be associated with earlier presentation.

Molar pregnancy may also be associated with an unusually early onset.

Slide 8 · Why proteinuria is not essential for diagnosis

Modern frameworks do not require proteinuria when new hypertension accompanies qualifying organ dysfunction.

Renal insufficiency, thrombocytopenia, liver injury, pulmonary edema and neurologic features must be assessed.

Clinical classification should not depend on edema alone: It is nonspecific in pregnancy.

Textbook language highlights edema and proteinuria; This slide uses contemporary criteria.

Slide 9 · ACOG thresholds: Hypertension and proteinuria

Assessment

Threshold or interpretation

New hypertension

Systolic ≥140 mm Hg or diastolic ≥90 mm Hg on two occasions ≥4 h apart, ordinarily after 20 weeks.

Severe-range pressure

Systolic ≥160 mm Hg or diastolic ≥110 mm Hg.

24-hour urinary protein

≥300 mg per 24 hours.

Spot urine protein/creatinine

≥0.3 mg/mg.

Absence of proteinuria

Does not exclude preeclampsia if eligible organ dysfunction is present.

Slide 10 · ACOG: Major severe-feature findings

Organ domain

Clinically significant finding

Pressure

Systolic ≥160 or diastolic ≥110 mm Hg.

Hematologic

Platelet count <100,000/µL.

Renal

Creatinine >1.1 mg/dL or doubling from baseline without another renal disease.

Hepatic

Transaminases >2 times normal; persistent severe RUQ/epigastric pain may be relevant.

Pulmonary

Pulmonary edema.

Neurologic

New persistent headache unresponsive to medication or visual symptoms.

Slide 11 · Eclampsia: Neurologic escalation

Seizures mark severe neurologic involvement in the preeclampsia spectrum.

Severe headache and visual symptoms may precede convulsions but are not obligatory.

Eclampsia may progress to coma and maternal death.

Alternative causes of seizures must be considered clinically.

Slide 12 · HELLP is a multisystem vascular complication

H — hemolysis

Microangiopathic red-cell injury

Reflects small-vessel damage and consumption

EL — enzymes

Hepatic enzyme elevation

Can accompany hepatic microthrombi, necrosis or hemorrhage

LP — platelets

Thrombocytopenia

Platelet consumption in systemic endothelial/coagulation injury

Slide 13 · Normal spiral-artery remodeling produces low resistance

Physiologic pregnancy

Extravillous trophoblast enters vessel wall

Smooth muscle coat is lost

Broad, low-resistance uteroplacental channel

Adequate maternal perfusion of intervillous space

Schematic cross-section, not histology

Slide 14 · Physiologic conversion of the placental bed

Extravillous invasion

Fetal trophoblast enters decidua and maternal spiral-artery walls

Wall remodeling

Vascular muscle is lost and trophoblast replaces endothelial lining

High-capacity flow

Dilated, low-resistance maternal vessels perfuse intervillous space

Slide 15 · Failed spiral-artery transformation in preeclampsia

Preeclampsia

Inadequate extravillous trophoblast invasion

Persistence of arterial smooth muscle

Relatively narrow, high-resistance lumen

Reduced capacity to meet late-gestational flow demand

Schematic cross-section, not histology

Slide 16 · Spiral arteries: Normal versus failed transformation

Physiologic remodeling

Muscle loss · expanded lumen

Inadequate remodeling

Persistent media · higher resistance

Slide 17 · The central placental hemodynamic defect

Shallow trophoblast implantation leaves maternal spiral arteries inadequately remodeled.

Narrow, relatively muscular vessels limit adaptive delivery of maternal blood.

Later gestation increases flow requirements beyond what these vessels can support.

The resulting placental underperfusion is a proposed initiating stimulus.

Slide 18 · A two-stage model connects placenta and mother

Stage 1: Placenta

Poor remodeling → ischemic or stressed placenta

Circulating mediators

Antiangiogenic factors enter maternal circulation

Stage 2: Mother

Endothelial dysfunction → hypertension, leakage and thrombosis

Conceptual model: Placental pathology begins before overt maternal symptoms

Slide 19 · From trophoblast to clinical presentation

Shallow invasion

Persistent resistance vessels

Placental hypoxia

Hypoxic stress and mediator release

Endothelial dysfunction

Impaired vasodilator and antithrombotic signaling

Maternal syndrome

Hypertension · proteinuria · edema · organ injury

Slide 20 · SFlt-1: Soluble VEGF receptor activity

Placenta-derived soluble fms-like tyrosine kinase 1 (sFlt-1) is elevated model.

It binds/antagonizes vascular endothelial growth factor (VEGF) signaling.

Reduced VEGF-dependent endothelial support contributes to dysfunction.

The source treats this as a major proposed mechanistic bridge, not a sole cause.

Slide 21 · SFlt-1 links placenta to endothelial dysfunction

Placental stress

Hypoperfusion is proposed to trigger factor release

↑ circulating sFlt-1

Soluble ligand-binding receptor rises

↓ effective VEGF

VEGF signaling is antagonized

Endothelial effects

Vasoconstriction, barrier injury and reduced PGI₂ support

Slide 22 · Soluble endoglin antagonizes TGF-β signaling

Soluble endoglin is another placenta-derived antiangiogenic factor emphasized by Robbins.

It antagonizes transforming growth factor-β (TGF-β) signaling.

TGF-β normally contributes to endothelial nitric oxide production.

Consequent reduction in vasodilatory signaling may increase systemic vascular tone.

Slide 23 · Endoglin–TGF-β–nitric oxide axis

↑ soluble endoglin

An antiangiogenic circulating influence

↓ TGF-β action

Endothelial signal is antagonized

↓ endothelial NO

Less vasodilator synthesis

↑ vasoconstriction

Contributes to hypertension and tissue hypoperfusion

Slide 24 · Why prostacyclin matters for thrombosis

VEGF stimulates endothelial production of prostacyclin (PGI₂).

PGI₂ has vasodilatory and antithrombotic properties.

VEGF antagonism by sFlt-1 may reduce PGI₂ generation.

Reduced antithrombotic protection and procoagulant release favor microthrombosis.

Slide 25 · Antiangiogenic imbalance converges on injury

SFlt-1 → VEGF blockade

Less PGI₂-supported antithrombotic signaling

Endoglin → TGF-β block

Less nitric oxide-mediated vasodilation

Endothelial dysfunction

Hypertension + leak + microvascular thrombosis

Slide 26 · Three endothelial consequences explain the phenotype

Increased tone

Generalized vasoconstriction

Systemic hypertension and organ hypoperfusion

Barrier failure

Increased vascular permeability

Proteinuria and fluid extravasation

Prothrombotic state

Thrombi in arterioles/capillaries

Tissue ischemia, hemolysis and platelet use

Slide 27 · Evidence supporting a placental mediator model

Clinical manifestations commonly improve following placental delivery.

Maternal sFlt-1 and soluble endoglin levels are markedly increased in the source description.

Experimental overexpression in pregnant rats induces hypertension, proteinuria and HELLP-like effects.

Animal experiments support causality but do not establish identical biology in every patient.

Slide 28 · Heterogeneity and mechanistic caution

The source describes a predominant pathway, not a uniform molecular cause of all disease.

Placental vascular pathology and clinical severity do not map one-to-one in every pregnancy.

Antiangiogenic factors are mechanistically informative; They do not replace a clinical diagnosis.

Avoid treating a schematic sequence as a unique, fully proved causal chain.

Slide 29 · Placental pathology: Maternal vascular malperfusion

Maternal vascular malperfusion (MVM) is inadequate maternal supply to the intervillous space.

In preeclampsia, MVM appears as a constellation of placental and decidual lesions.

The findings include a small placenta, infarction, ischemic villous changes, hematoma and decidual arteriopathy.

Each finding supports a vascular pattern but should be interpreted in clinical and gestational context.

Slide 30 · Placental hypoplasia reflects impaired perfusion

Placental hypoplasia

Reduced placental mass is one feature of maternal vascular malperfusion.

Interpret weight against gestational age rather than in isolation.

Schematic, not gross pathology

Slide 31 · Placental infarction: Consequence of ischemia

Placental infarct

An ischemic focus of villous necrosis follows impaired maternal perfusion.

Infarcts may be extensive or multiple in preeclampsia.

Schematic, not gross pathology

Slide 32 · Villous stress and accelerated maturation

Chorionic villi exposed to inadequate maternal perfusion show ischemic stress.

The source specifically describes increased syncytial knots.

Smaller, shrunken distal villi can accompany altered intervillous spacing.

The microscopic pattern should be interpreted with gestational age and sampling context.

Slide 33 · Increased syncytial knots: Schematic villous change

Typical villous contour

Exaggerated knotting

Illustrative schematic; Not a photomicrograph

Slide 34 · Distal villous hypoplasia: Altered villous architecture

Appropriate villous development

Distal villous hypoplasia

Schematic of relative villous form, not a diagnostic slide

Slide 35 · Retroplacental hematoma and vessel instability

Retroplacental hematoma

Hemorrhage accumulates between maternal surface and uterine wall.

May reflect vessel instability and accompany placental abruption.

Schematic, not gross pathology

Slide 36 · Decidual arteriopathy: Unremodeled maternal vessel

Preeclampsia

Inadequate extravillous trophoblast invasion

Persistence of arterial smooth muscle

Relatively narrow, high-resistance lumen

Reduced capacity to meet late-gestational flow demand

Schematic cross-section, not histology

Slide 37 · Acute atherosis: Characteristic vessel injury

Decidual spiral arteries may show intimal lipid deposition (acute atherosis).

Associated findings include fibrinoid necrosis and inadequate physiologic remodeling.

The lesion is part of the decidual vascular injury spectrum in MVM.

Atherosis should not be treated as specific to preeclampsia in isolation.

Slide 38 · Placental vascular lesions: Mechanism and finding

Lesion

Morphologic correlate

Mechanistic interpretation

Hypoplasia

Placenta small for gestational age

Reduced placental growth/perfusion

Infarction

Foci of ischemic villous necrosis

Reduced maternal blood supply

Distal villous hypoplasia

Small distal villi; expanded maternal space

Abnormal villous development

Retroplacental hematoma

Blood between placenta and uterine wall

Uteroplacental vessel bleeding

Decidual arteriopathy

Thrombi, failed remodeling, fibrinoid damage, atherosis

Maternal inflow vasculopathy

Slide 39 · Interpreting pathology without overdiagnosis

Neither a single placental infarct nor an isolated syncytial knot proves preeclampsia.

The useful diagnosis is a coherent maternal vascular malperfusion pattern.

Gestational age, placental weight, sampling and clinical hypertensive history remain important.

The placenta demonstrates injury; Maternal clinical criteria establish the syndrome.

Slide 40 · One endothelial injury pattern, multiple target organs

Diffuse endothelial

Dysfunction

Kidney

Proteinuria · AKI

Brain

Headache · seizure

Lung

Pulmonary edema

Liver

Enzyme elevation

Coagulation

Thrombosis · DIC

Placenta

Ischemia · FGR

Slide 41 · Hypertension: Vessel tone is the key link

Antiangiogenic signals

SFlt-1/endoglin influence endothelium

Loss of vasodilation

Less nitric oxide/PGI₂ support

Systemic resistance

Arteriolar tone increases → maternal hypertension

Slide 42 · Renal proteinuria: Glomerular barrier injury

Maternal endotheliopathy

Systemic microvascular dysfunction

Renal vascular injury

Glomerular barrier becomes abnormal

Protein leakage

Urinary protein excretion increases

Slide 43 · Renal involvement extends beyond proteinuria

Acute renal failure can complicate severe preeclampsia.

Renal injury is part of the syndrome even when urinary protein is not dominant.

Maternal perfusion and microvascular injury are both relevant mechanisms.

Creatinine assessment is necessary when severe disease is suspected.

Slide 44 · Edema reflects endothelial permeability

Endothelial dysfunction

Barrier regulation deteriorates

Vascular fluid leakage

Fluid extravasates into interstitial spaces

Tissue fluid accumulation

Peripheral edema and, in severe disease, pulmonary edema

Slide 45 · Neurologic warning signs and eclampsia

Headache and visual disturbances indicate possible severe disease.

Seizures signify major central nervous system involvement.

Stroke is among the principal causes of life-threatening maternal morbidity.

Absence of a preceding symptom does not ensure freedom from seizure risk.

Slide 46 · Hepatic injury: Microthrombi and necrosis

Chapter 22 describes fibrin thrombi in portal capillaries with focal hemorrhagic necrosis.

Chapter 18 emphasizes periportal sinusoidal fibrin and hemorrhage into the space of Disse.

Hepatocellular injury can elevate aminotransferases.

Severe hepatic dysfunction or coagulopathy signals potentially lethal disease.

Slide 47 · Subcapsular hepatic hemorrhage can rupture

Hepatic microvascular injury

Fibrin thrombi and necrotic foci

Focal hemorrhage/hematoma

Subcapsular blood accumulates

Capsular dissection

Severe cases may rupture Glisson capsule

A dangerous complication; Not a routine finding in uncomplicated disease

Slide 48 · HELLP syndrome: Mechanistic integration

Hemolysis: Erythrocyte injury in a microangiopathic circulation.

Elevated liver enzymes: Hepatic ischemic/hemorrhagic injury.

Low platelets: Consumption associated with vascular/coagulation activation.

The constellation warrants recognition as serious preeclampsia-spectrum disease.

Slide 49 · Microthrombi connect coagulation and bleeding

Endothelial activation

Loss of antithrombotic endothelial function

Small-vessel thrombi

Thrombi particularly involve placenta, liver, kidneys and brain

Consumption and injury

Thrombocytopenia, ischemia and, in severe cases, DIC

Slide 50 · Pulmonary edema: Permeability meets hemodynamics

Generalized endothelial barrier injury permits fluid movement into extravascular compartments.

Pulmonary edema is a severe systemic manifestation.

Fluid-management decisions require specialist clinical assessment.

Respiratory symptoms should not be dismissed as normal pregnancy discomfort.

Slide 51 · Fetal consequences originate in placental supply

Abnormal uteroplacental inflow restricts effective placental nutrient and oxygen exchange.

Fetal growth restriction may accompany placental underperfusion.

Placental infarction and abruption can acutely compromise fetal status.

Early delivery itself carries neonatal risks that must be weighed against maternal risk.

Slide 52 · Clinicopathologic distinctions

Feature

Gestational HTN

Preeclampsia / eclampsia

Maternal blood pressure

Elevated after 20 weeks

Elevated; may reach severe range

Proteinuria

Not required / typically absent

May occur, but not required

Organ dysfunction

Absent by definition

Can involve kidney, liver, platelets, lung, CNS

Seizures

Not defining

Eclampsia when attributable to disorder

Placental MVM

Not diagnostic

Common associated pathology

Slide 53 · Differential diagnosis: Hepatic and microangiopathic disease

Preeclampsia/HELLP may share thrombocytopenia and transaminitis with other syndromes.

Acute fatty liver of pregnancy can cause severe hepatic dysfunction with microvesicular steatosis.

Thrombotic microangiopathies require their own clinical/laboratory evaluation.

Placental findings assist context but cannot independently separate every maternal syndrome.

Slide 54 · Maternal evaluation: Connect testing to mechanisms

Assessment

Question answered

Serial blood pressure

Is hypertension persistent or severe?

Urinary protein assessment

Is glomerular barrier injury evident?

Platelet count / blood film

Is platelet consumption or hemolysis present?

Creatinine

Is renal function impaired?

Liver enzymes

Is hepatocellular injury present?

Symptoms / respiratory status

Are neurologic or pulmonary severe features present?

Fetal assessment

Is uteroplacental function compromised?

Slide 55 · Management decision rests on maternal and fetal risk

Assess gestational age

Preterm or term pregnancy

Determine severity

Severe features, HELLP, eclampsia, fetal compromise?

Delivery versus monitoring

Maternal stabilization and delivery, or close expectant care if appropriate

Slide 56 · Term and preterm management principles

Term pregnancy

Delivery is generally the treatment of choice.

Maternal blood pressure and severe features require assessment.

Manage possible seizures and complications.

Preterm pregnancy

Without severe features, selected patients may be monitored closely.

Severe features or fetal compromise may require earlier delivery.

Maternal stabilization and fetal maturity are balanced.

Slide 57 · Indications for urgent delivery account

Eclampsia and preeclampsia with severe features.

HELLP syndrome.

Fetal compromise or rapidly evolving maternal organ injury.

Clinical stabilization is essential while arranging definitive obstetric management.

Slide 58 · Delivery removes the major placental driver

Removal of the placenta typically leads to rapid clinical improvement.

That hypertension and proteinuria usually settle within 1–2 weeks.

Postpartum-onset or persistent hypertension may still occur, requiring surveillance.

Resolution after delivery supports, but does not individually prove, placental causality.

Slide 59 · Long-term vascular implications persist

That some survivors later develop hypertension and microalbuminuria.

The textbook associates a prior preeclampsia pregnancy with approximately doubled long-term cardiovascular risk.

Pregnancy can therefore reveal underlying or future vascular susceptibility.

Long-term cardiovascular risk review matters after apparent obstetric recovery.

Slide 60 · Case: New hypertension without proteinuria

Clinical vignette

At 32 weeks, a previously normotensive pregnant patient develops sustained blood pressure of 162/112 mm Hg, severe headache and visual disturbance. Urinary protein is not detected.

Interpretation

Does lack of proteinuria exclude preeclampsia?

Which features indicate danger?

What maternal systems need evaluation?

Slide 61 · Case: Pathology–fetal correlation

Clinical vignette

A placenta from a pregnancy complicated by hypertension and fetal growth restriction is small for gestational age, with multiple infarcts, distal villous hypoplasia and unremodeled decidual arteries.

Interpretation

Identify the injury pattern.

Which maternal vessels initiate the process?

Why is fetal growth affected?

Slide 62 · Case: Hepatic warning pattern

Clinical vignette

At 34 weeks, a patient with pregnancy-associated hypertension has worsening right upper quadrant pain, elevated aminotransferases, hemolysis and falling platelet count.

Interpretation

What syndrome is suggested?

What hepatic lesions explain pain/injury?

Why is the situation time-critical?

Slide 63 · Pathogenesis, morphology and clinical expression

Initiating / mediator event

Pathology

Clinical expression

Inadequate spiral-artery remodeling

Placental MVM, infarction

Fetal growth restriction

sFlt-1 / endoglin excess

Endothelial dysfunction

Hypertension, edema, proteinuria

Reduced PGI₂ / procoagulant signals

Microvascular thrombosis

HELLP, ischemic injury

Hepatic microvascular injury

Periportal fibrin and necrosis

Transaminitis, RUQ pain, hematoma

Slide 64 · High-yield synthesis: Five causal connections

Placental bed

Shallow invasion

Persistent high-resistance spiral arteries

Angiogenic imbalance

↑ sFlt-1 · ↑ endoglin

Less VEGF/TGF-β protective signaling

Systemic organs

Vasoconstriction · leak · thrombosis

Kidney, brain, liver, lung and placenta affected

Slide 65 · Final diagnostic and morphologic cautions

Do not make edema or proteinuria mandatory criteria under modern classification.

Do not diagnose preeclampsia from an isolated placental lesion without clinical findings.

Do not assume all preeclampsia follows one identical antiangiogenic mechanism.

Identify HELLP, severe hypertension and neurologic symptoms promptly.

Slide 66 · References and source transparency

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th edition (2026): Chapter 22, pages 937–939.

Additional Robbins context: maternal vascular malperfusion (Chapter 22) and hepatic pathology (Chapter 18, pages 786–787).

ACOG Practice Bulletin 222 (2020, reaffirmed 2026): diagnostic and management guidance.

ISSHP 2021 recommendations: international clinical criteria and recognition of nonproteinuric disease.