Preeclampsia and Eclampsia

Slide 1 · Preeclampsia and Eclampsia

Hepatic pathology, HELLP syndrome, and maternal vascular injury

A pathology-centered review of maternal vascular injury

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain placental and maternal endothelial mechanisms of preeclampsia.

Recognize periportal fibrin, hemorrhage, and hepatocellular necrosis.

Relate HELLP syndrome to hepatic injury and systemic microangiopathy.

Identify subcapsular hematoma, rupture risk, and key differentials.

Slide 3 · A systemic syndrome with a hepatic phenotype

Preeclampsia is a pregnancy-associated syndrome of maternal endothelial dysfunction.

Hypertension accompanies variable renal, hematologic, neurologic, and hepatic manifestations.

Liver abnormalities may be prominent despite limited preceding symptoms.

Abnormal placentation

Placental vascular stress

Maternal endothelial dysfunction

Hepatic microvascular injury

Slide 4 · Preeclampsia is not synonymous with proteinuria

The Chapter 22 definition emphasizes new hypertension after 20 weeks with additional clinical or organ findings.

Proteinuria and edema are common manifestations, not a complete description of the syndrome.

Gestational hypertension

New pregnancy-associated hypertension

No other findings of preeclampsia

Preeclampsia

Hypertension plus systemic involvement

Renal, cerebral, hepatic, or vascular effects

Slide 5 · Eclampsia denotes convulsive disease

Seizures signal severe central nervous system involvement in preeclampsia.

Neurologic progression may involve coma and death.

Eclampsia can coexist with major hepatic hemorrhagic complications.

Preeclampsia

Severe cerebral involvement

Convulsions (eclampsia)

Threat to maternal survival

Slide 6 · Clinical severity reflects multisystem injury

Diffuse endothelial dysfunction links hypertension to organ injury.

The liver is one target among kidney, brain, lung, and placenta.

A normal-looking pregnancy course does not exclude evolving severe disease.

Maternal endothelium

Kidney: Proteinuria / failure

Liver: Enzyme elevation / bleeding

Brain: Headache / seizures

Lung: Pulmonary edema

Slide 7 · HELLP identifies a distinctive clinical constellation

HELLP combines hemolysis, elevated liver enzymes, and low platelet count.

The triad reflects systemic microangiopathy and hepatic involvement.

Hepatic disease may dominate the presentation of preeclampsia.

H — Hemolysis

EL — Elevated liver enzymes

LP — Low platelets

Slide 8 · Pregnancy-related liver disorders need separation

Chapter 18 discusses three major pregnancy-specific hepatic entities.

Overlapping symptoms make clinicopathologic discrimination important.

Preeclampsia / HELLP

Endothelial injury, fibrin, hemorrhage

Hypertension and platelet abnormalities

Other pregnancy liver disease

Acute fatty liver: Microvesicular fat

Cholestasis: Pruritus, bile retention

Slide 9 · The placenta is central to pathogenesis

Maternal symptoms usually regress after delivery of the placenta.

Placental dysfunction precedes the maternal clinical syndrome.

Placenta-derived circulating mediators help explain distant organ injury.

Placental bed abnormality

Placental ischemic stress

Circulating mediators

Maternal endothelial injury

Slide 10 · Normal spiral artery remodeling

Extravillous trophoblast remodels decidual spiral arteries early in pregnancy.

Smooth muscle is replaced, producing dilated low-resistance vessels.

This transformation supports increasing uteroplacental perfusion.

Normal uteroplacental vessel

Wide lumen

Loss of smooth muscle / low resistance

Schematic

Slide 11 · Failed remodeling increases placental resistance

Shallow trophoblast invasion leaves maternal vessels inadequately remodeled.

Persistent high-resistance vessels limit placental perfusion.

Demand increases as gestation progresses, amplifying placental stress.

Inadequately remodeled vessel

Narrow lumen

Persistent muscular wall / higher resistance

Schematic

Slide 12 · Placental ischemia is the mechanistic hinge

Reduced perfusion establishes a setting for hypoxia and trophoblast stress.

The ischemic placenta may release factors acting throughout the maternal vasculature.

This helps connect an early implantation defect with late maternal disease.

High-resistance spiral arteries

Impaired uteroplacental flow

Placental hypoxic stress

Circulating endothelial mediators

Slide 13 · SFLT-1 antagonizes proangiogenic signaling

Placental soluble fms-like tyrosine kinase-1 (sFLT-1) increases in preeclampsia.

SFLT-1 antagonizes vascular endothelial growth factor (VEGF) activity.

VEGF signaling loss contributes to endothelial dysfunction.

Placental sFLT-1

Reduced VEGF signaling

Endothelial instability

Vascular dysfunction

Slide 14 · Soluble endoglin perturbs TGF-β signaling

Circulating soluble endoglin rises in preeclampsia.

It antagonizes transforming growth factor-β (TGF-β)-dependent pathways.

Reduced nitric oxide generation may favor maternal vasoconstriction.

Soluble endoglin

Reduced TGF-β signaling

Less endothelial nitric oxide

Vasoconstriction

Slide 15 · Antiangiogenic excess has systemic consequences

Angiogenic imbalance disrupts vascular homeostasis rather than injuring only the placenta.

VEGF and TGF-β pathway inhibition have complementary endothelial effects.

SFLT-1 excess

VEGF antagonism

Endothelial instability / lower PGI₂

Soluble endoglin excess

TGF-β antagonism

Reduced NO-dependent vasodilation

Slide 16 · Reduced endothelial vasodilators favor hypertension

Loss of nitric oxide signaling increases vascular tone.

Reduced prostacyclin (PGI₂) removes vasodilatory and antithrombotic effects.

Systemic vasoconstriction promotes hypertension and tissue hypoperfusion.

Endothelial injury

↓ nitric oxide / ↓ PGI₂

Vasoconstriction

Hypertension + hypoperfusion

Slide 17 · Increased permeability explains edema and proteinuria

Endothelial barrier damage promotes abnormal movement of fluid and proteins.

Renal vascular injury contributes to proteinuria.

Peripheral and pulmonary edema reflect increased vascular leak.

Systemic endothelial dysfunction

Barrier permeability increases

Protein / fluid escape

Proteinuria and edema

Slide 18 · Hypercoagulability drives microvascular thrombi

Preeclampsia produces a prothrombotic vascular environment.

Small vessels in liver, kidney, brain, and placenta may contain thrombi.

Reduced endothelial PGI₂ may contribute to local platelet activation.

Endothelial disturbance

Procoagulant balance

Microvascular thrombosis

Organ ischemia / hemorrhage

Slide 19 · Placenta-to-liver injury pathway

Hepatic involvement arises downstream of the systemic vascular disorder.

Fibrin deposition and hemorrhage occur in periportal microvasculature.

Liver-cell necrosis and biochemical abnormalities can follow.

Placental dysfunction

Systemic vascular / coagulation injury

Periportal fibrin and hemorrhage

Hepatocellular injury

Slide 20 · Hepatic injury must be mapped by lobular location

Portal tracts lie at the lobule periphery; Terminal hepatic venules lie centrally.

The periportal region is the characteristic focus of fibrin-linked injury in preeclampsia.

Zonal location helps distinguish other circulatory liver disorders.

Simplified hepatic lobule

Portal tracts: Peripheral / periportal

Central venule: Center / centrilobular

Slide 21 · The periportal sinusoid is a key injury site

Sinusoids carry blood through hepatocyte plates and communicate with the space of Disse.

Periportal microvessels are exposed to systemic coagulation and endothelial injury.

Liver architecture provides the substrate for localized hemorrhage.

Simplified periportal microvasculature

Blue sinusoids between tan hepatocyte plates

Schematic

Slide 22 · Fibrin deposition begins the morphologic cascade

Preeclampsia can deposit fibrin within periportal sinusoids.

The finding reflects hepatic microvascular coagulation abnormalities.

Fibrin deposition is linked to subsequent hemorrhagic parenchymal injury.

Simplified periportal microvasculature

Red fibrin deposits lie within blue sinusoids

Schematic

Slide 23 · Hemorrhage may extend into the space of Disse

Periportal sinusoidal injury permits red-cell extravasation into the perisinusoidal space.

Perisinusoidal hemorrhage compromises adjacent hepatocytes.

Vascular injury and local tissue damage are anatomically continuous.

Simplified periportal microvasculature

Hemorrhage crosses into perisinusoidal space

Schematic

Slide 24 · Periportal hepatocytes develop coagulative necrosis

Fibrin and hemorrhage are associated with periportal hepatocyte death.

Coagulative necrosis in the affected parenchyma.

Injury can be patchy and unevenly distributed.

Simplified periportal microvasculature

Hepatocytes injured adjacent to hemorrhage

Schematic

Slide 25 · The hepatic histologic sequence is causal

Microvascular fibrin obstructs or disrupts sinusoidal flow.

Hemorrhage into the space of Disse accompanies vascular damage.

Adjacent periportal hepatocytes undergo necrosis.

Periportal fibrin

Perisinusoidal hemorrhage

Hepatocyte injury

Coagulative necrosis

Slide 26 · Liver damage may be focal rather than diffuse

Chapter 22 describes irregular, focal hepatic hemorrhages.

Subcapsular and intraparenchymal distributions may coexist.

Histology

Fibrin thrombi in portal capillaries

Foci of hemorrhagic necrosis

Gross distribution

Irregular parenchymal hemorrhage

Subcapsular bleeding / hematoma

Slide 27 · A subcapsular hematoma can develop

Blood may dissect beneath Glisson capsule in eclampsia.

The hematoma can expand while contained by the overlying capsule.

This lesion is a high-risk manifestation of severe hepatic disease.

Liver capsule and parenchyma (section)

Glisson capsule

Subcapsular blood

Schematic

Slide 28 · Subcapsular expansion threatens hepatic rupture

Continued accumulation of blood raises mechanical stress on Glisson capsule.

Capsular disruption can produce catastrophic hemorrhage.

Morphologic recognition is essential because clinical deterioration can be abrupt.

Liver capsule and parenchyma (section)

Glisson capsule

Subcapsular blood

Schematic

Slide 29 · Hepatic hematoma and rupture are distinct stages

A contained collection and a disrupted capsule should not be conflated.

Both lie on the spectrum of severe hepatic hemorrhagic injury.

Subcapsular hematoma

Blood dissects below an intact capsule

Potential for expansion

Hepatic rupture

Capsular integrity lost

Life-threatening intraperitoneal bleeding

Slide 30 · Periportal and centrilobular patterns differ

Preeclamptic injury is described periportally with sinusoidal fibrin.

Cardiac congestion produces centrilobular sinusoidal engorgement and hepatocyte atrophy.

Locating injury by zone strengthens differential diagnosis.

Simplified hepatic lobule

Portal tracts: Peripheral / periportal

Central venule: Center / centrilobular

Slide 31 · Do not confuse HELLP liver with nutmeg liver

Interleaved Chapter 18 text describes cardiac passive congestion, not preeclampsia.

The accompanying Fig. 18.47 is a passive congestion image, not HELLP histology.

Preeclampsia / HELLP

Periportal fibrin and hemorrhage

Coagulative necrosis

Passive hepatic congestion

Centrilobular sinusoidal congestion

Atrophy / hemorrhagic necrosis

Slide 32 · Hepatic enzyme elevation reports cell injury

Aminotransferase elevation may range from modest to severe.

The biochemical finding aligns with hepatocellular injury and necrosis.

Transaminase elevation alone does not specify the hepatic lesion.

Sinusoidal fibrin / hemorrhage

Hepatocyte injury

Enzyme release

Raised aminotransferases

Slide 33 · Bilirubin abnormalities may be relatively mild

Mild bilirubin elevation in hepatic preeclampsia.

Marked dysfunction or additional pathology warrants broader differential consideration.

Common hepatic pattern

Aminotransferases elevated

Bilirubin sometimes mildly elevated

Severe systemic injury

Coagulopathy or progressive organ failure

Potentially life-threatening disease

Slide 34 · Coagulopathy is a warning of advanced disease

Hepatic dysfunction severe enough to cause coagulopathy marks advanced disease.

Endothelial injury and microvascular thrombosis may coexist with bleeding.

Hemorrhagic complications require urgent clinical recognition.

Vascular injury

Microthrombi / hepatic necrosis

Hemostatic derangement

Potential catastrophic bleeding

Slide 35 · HELLP: Hemolysis reflects microangiopathy

Endothelial injury and narrowed microvessels may damage circulating erythrocytes.

The hemolytic component occurs alongside thrombocytopenia and liver injury.

Hemolysis should be interpreted as systemic, not isolated hepatic, disease.

Microvascular injury

Erythrocyte shear damage

Hemolysis

HELLP component H

Slide 36 · HELLP: Elevated enzymes indicate liver-cell damage

The EL component records hepatocellular enzyme release.

Underlying liver lesions include fibrin-associated periportal necrosis.

The degree of biochemical elevation does not directly reveal hematoma size.

Periportal vascular injury

Hepatocyte necrosis

Serum enzyme rise

HELLP component EL

Slide 37 · HELLP: Low platelets accompany thrombosis

Increased platelet consumption contributes to thrombocytopenia.

Thrombotic microangiopathy and bleeding risk can coexist.

Low platelets complete the HELLP triad when hemolysis and enzyme elevation accompany them.

Vascular procoagulant state

Platelet recruitment / consumption

Thrombocytopenia

HELLP component LP

Slide 38 · HELLP integrates three injured compartments

Blood: Hemolysis is evidence of microangiopathic injury.

Liver: Hepatocyte injury yields elevated aminotransferases.

Hemostasis: Thrombocytopenia signals platelet consumption.

Microvascular red-cell injury

Hepatic parenchymal injury

Platelet depletion

Slide 39 · The HELLP phenotype may mask preeclampsia

Chapter 18 notes that subclinical hepatic disease may be the leading manifestation.

A narrow hypertension-only approach may miss important systemic pathology.

Obvious preeclampsia

Maternal hypertension / edema

Recognizable systemic symptoms

HELLP-dominant presentation

Enzyme and platelet abnormalities

Hepatic injury may be prominent

Slide 40 · Placental vascular malperfusion is the upstream lesion

The placenta may be small and show prominent infarction.

Maternal vascular malperfusion supports a placental perfusion disorder.

Placental morphology explains the fetal component of disease.

Spiral artery remodeling failure

Maternal vascular malperfusion

Placental ischemic injury

Fetal growth compromise

Slide 41 · Placental infarcts reflect ischemic supply failure

Placental infarcts may be extensive or numerous.

The finding fits maternal vessel resistance and compromised perfusion.

Maternal vascular problem

High-resistance spiral arteries

Reduced placental perfusion

Placental consequence

Ischemic infarction

Reduced functional placental tissue

Slide 42 · Distal villous hypoplasia signals chronic malperfusion

Small, shrunken villi with increased maternal vascular space.

Increased syncytial knotting accompanies exaggerated ischemic maturation.

Villous pattern

Small distal villi

Relatively wide intervillous spaces

Trophoblast change

Increased syncytial knots

Feature of chronic perfusion stress

Slide 43 · Decidual vessels may show acute atherosis

Abnormal decidual arteries can retain their resistance-vessel phenotype.

Fibrinoid necrosis, lipid-laden intimal change, or thrombi may appear.

These lesions reinforce the uteroplacental vascular origin of disease.

Abnormal decidual artery

Narrow lumen

Fibrinoid / thrombotic change possible

Schematic

Slide 44 · Retroplacental hematoma reflects vessel instability

Abnormal uteroplacental vessels may bleed behind the placenta.

Retroplacental hemorrhage links placental malperfusion with acute bleeding.

Chronic component

Failed maternal vessel remodeling

Placental ischemic lesions

Acute component

Uteroplacental vascular instability

Retroplacental hematoma

Slide 45 · Renal involvement explains proteinuria

The syndrome affects systemic endothelium, including renal microvessels.

Increased permeability supports urinary protein loss.

Severe cases can develop acute renal dysfunction.

Endothelial dysfunction

Renal microvascular injury

Proteinuria

Possible renal failure

Slide 46 · Neurologic escalation defines eclampsia

Headache and visual disturbance may indicate severe features.

Seizures distinguish eclampsia from preeclampsia.

Cerebral involvement may culminate in coma and fatal complications.

Maternal vascular dysfunction

Headache / visual disturbance

Seizures

Eclampsia

Slide 47 · Pulmonary edema is a vascular-leak consequence

Excess vascular permeability can shift fluid into the pulmonary interstitium.

Preeclampsia can cause pulmonary edema and respiratory compromise.

This is systemic endothelial disease, not a primary lung disorder.

Endothelial barrier dysfunction

Increased fluid escape

Pulmonary edema

Respiratory compromise

Slide 48 · Fetal effects arise through the placenta

Maternal malperfusion limits effective placental nutrient and oxygen delivery.

Fetal growth restriction may accompany severe maternal disease.

Maternal and fetal consequences share an upstream vascular mechanism.

Maternal spiral artery failure

Placental malperfusion

Reduced fetal support

Growth restriction

Slide 49 · Clinical features often evolve sequentially

Hypertension and edema may be noticed before proteinuria.

Headache or visual symptoms indicate neurologic progression.

Rapid deterioration may culminate in seizures or multiorgan dysfunction.

Hypertension / edema

Proteinuria / organ findings

Neurologic warning signs

Eclampsia or severe disease

Slide 50 · Gestational hypertension lacks the systemic pattern

A diagnosis based only on elevated blood pressure does not capture preeclampsia.

Additional vascular, renal, hematologic, or hepatic findings change the syndrome classification.

Gestational hypertension

New hypertension during pregnancy

No associated preeclampsia manifestations

Preeclampsia

New hypertension after 20 weeks

Associated systemic / organ findings

Slide 51 · HELLP versus acute fatty liver of pregnancy

Both can present in late gestation with elevated aminotransferases.

Their hallmark liver morphologies differ and overlap is possible clinically.

HELLP / preeclampsia

Microangiopathy and thrombocytopenia

Periportal fibrin / hemorrhagic necrosis

Acute fatty liver of pregnancy

Hepatic metabolic dysfunction

Diffuse microvesicular steatosis

Slide 52 · HELLP versus intrahepatic cholestasis

Pruritus and bile-salt retention characterize intrahepatic cholestasis.

Hemolysis, low platelets, and periportal vascular injury indicate a different process.

HELLP / preeclampsia

Microvascular thrombotic injury

Hypertension / hemolysis / low platelets

Pregnancy cholestasis

Pruritus in later pregnancy

Canalicular bile-transport dysfunction

Slide 53 · Pregnancy liver syndromes: Three mechanisms

Systemic endothelial injury, hepatocyte metabolic injury, and bile retention represent different mechanisms.

Clinicopathologic integration is needed when liver tests are abnormal in pregnancy.

Entity / domain

Mechanism / test

Key interpretation

Preeclampsia / HELLP

Endothelial and microvascular injury

Periportal fibrin / hemorrhage

Acute fatty liver

Mitochondrial fatty-acid metabolism

Microvesicular steatosis

Intrahepatic cholestasis

Impaired canalicular bile handling

Cholestatic symptoms

Slide 54 · Biochemical testing follows the suspected lesion

The pattern, not a single isolated laboratory result, guides interpretation.

This slide states relevant test domains; No unstated diagnostic cutoffs are implied.

Entity / domain

Mechanism / test

Key interpretation

Hepatocellular injury

Serum aminotransferases

Increased in hepatic preeclampsia

Hemolysis / platelets

Evidence of hemolysis; Platelet count

HELLP pattern

Excretory / synthetic injury

Bilirubin; Coagulation profile

Severity and differential

Slide 55 · Morphology and labs must be interpreted together

Elevated enzymes support hepatocyte injury, not a unique diagnosis.

HELLP pattern supports systemic microangiopathy when clinically appropriate.

Hepatic hematoma or rupture is an anatomic emergency beyond the laboratory phenotype.

Clinical syndrome

Hematologic + hepatic tests

Anatomic complication assessment

Integrated diagnosis

Slide 56 · Severe features shift management toward delivery

Management depends on gestational age and maternal–fetal condition.

Eclampsia, HELLP, severe preeclampsia, or fetal compromise are delivery indications in the Robbins discussion.

Delivery removes the principal source of pathogenic placental factors.

Assess severity

Maternal / fetal risk

Severe disease or HELLP

Delivery

Slide 57 · Postpartum improvement supports placental causation

Hypertension and proteinuria usually resolve after delivery in the Robbins account.

The maternal vascular syndrome commonly improves as placental stimuli diminish.

Acute hepatic complications remain clinically important during recovery.

Placenta delivered

Pathogenic drive diminishes

Endothelial recovery

Clinical improvement

Slide 58 · Recovery does not erase future vascular risk

Chapter 18 emphasizes hepatic recovery in survivors.

Chapter 22 also notes later hypertension, microalbuminuria, and cardiovascular risk after preeclampsia.

Immediate hepatic recovery and long-term vascular susceptibility are distinct outcomes.

Short-term course

Liver injury often resolves after pregnancy

Monitor acute severe complications

Long-term course

Increased future hypertension risk

Elevated later cardiovascular risk

Slide 59 · Case: Enzyme elevation and low platelets

A pregnant patient develops hypertension with elevated aminotransferases and thrombocytopenia.

Questions: What additional hematologic component completes HELLP? What hepatic microvascular lesion is expected?

Expected reasoning

Evaluate for hemolysis.

Expect periportal sinusoidal fibrin, hemorrhage, and necrosis.

Slide 60 · Case: Abrupt deterioration with hepatic bleeding

A patient with eclampsia develops evidence of an expanding hepatic hemorrhagic complication.

Questions: Which anatomic compartment may initially contain blood? Why can the lesion become catastrophic?

Expected reasoning

Blood may dissect under Glisson capsule.

Capsular rupture may cause catastrophic hemorrhage.

Slide 61 · Case: Differentiate two hepatic lesions

A histology description notes centrilobular sinusoidal congestion, hepatocyte atrophy, and a mottled cut surface.

Question: Does this represent the characteristic hepatic pattern of HELLP?

Expected reasoning

No. It matches passive hepatic congestion.

Preeclampsia favors periportal fibrin-associated hemorrhagic injury.

Slide 62 · Hepatic pathology: An integrated map

A placental vascular disorder drives systemic endothelial dysfunction.

Periportal coagulation and hemorrhage are the characteristic liver lesions.

HELLP and subcapsular hematoma represent serious clinicopathologic expressions.

Placental malperfusion

Endothelial / coagulation injury

Periportal necrosis

HELLP ± hepatic hematoma

Slide 63 · Diagnostic contrasts worth retaining

Anatomic location and dominant mechanism are more discriminating than liver enzyme elevation alone.

Entity / domain

Mechanism / test

Key interpretation

Preeclampsia / HELLP

Periportal

Fibrin, hemorrhagic injury

Passive congestion

Centrilobular

Blood pooling and atrophy

Acute fatty liver

Diffuse hepatocytic

Microvesicular steatosis

Slide 64 · Core morphology and clinical implications

Periportal sinusoidal fibrin with hemorrhage into the space of Disse can cause coagulative hepatocellular necrosis.

HELLP combines hemolysis, elevated liver enzymes, and thrombocytopenia.

Subcapsular hepatic hematoma may enlarge and rupture Glisson capsule.

The initiating mechanism lies in failed placental remodeling and systemic endothelial injury.

Slide 65 · Primary textbook sources

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th edition (2026). Chapter 18: Liver and Gallbladder, pp. 786–787.

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th edition (2026). Chapter 22: The Female Genital Tract, pp. 937–939.

Conceptual diagrams are original editable schematics; no synthetic images are presented as clinical or histologic specimens.