What is the pathophysiology of end‑organ damage in preeclampsia that leads to thrombocytopenia, elevated transaminases, increased serum creatinine, pulmonary edema, and visual disturbances?

Pathophysiology of End-Organ Damage in Preeclampsia

Core Mechanism: Systemic Endothelial Dysfunction

The end-organ manifestations of preeclampsia—thrombocytopenia, elevated liver enzymes, renal dysfunction, pulmonary edema, and visual disturbances—all result from widespread endothelial dysfunction triggered by placental ischemia and subsequent release of anti-angiogenic factors into maternal circulation. 1, 2

The pathophysiology follows a two-stage cascade 3, 1:

Stage 1: Placental Ischemia

• Abnormal placentation with shallow cytotrophoblast invasion causes defective spiral artery remodeling, resulting in high-resistance uteroplacental circulation and reduced placental perfusion 2, 4
• Placental hypoxia and oxidative stress trigger release of pathogenic factors into maternal circulation 3, 5

Stage 2: Maternal Systemic Response

• The stressed placenta releases excessive soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, which antagonize vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) 1, 2
• This angiogenic imbalance causes generalized endothelial dysfunction affecting multiple organ systems 6, 7

Specific End-Organ Manifestations

Thrombocytopenia (Decreased Platelet Count)

Platelet consumption occurs through activation of the coagulation cascade and increased platelet turnover secondary to widespread endothelial injury. 3, 8

• Endothelial dysfunction exposes subendothelial collagen, triggering platelet adhesion and aggregation 6, 5
• Platelet size increases in preeclampsia, indicating accelerated platelet turnover and consumption 3
• Microthrombi formation throughout the microcirculation further depletes circulating platelets 3
• Thrombocytopenia <100,000/μL indicates severe maternal organ dysfunction and correlates with disease severity 2, 8

Elevated Liver Enzymes

Hepatic involvement results from reduced perfusion causing ischemia, necrosis, and hemorrhage due to vasospasm and microvascular thrombosis. 2, 8

• Widespread endothelial dysfunction reduces hepatic blood flow, leading to hepatocellular ischemia and necrosis 3, 2
• Activation of the coagulation cascade further compromises hepatic microcirculation 2
• Liver capsule distension from hepatic edema and subcapsular hemorrhage causes right upper quadrant or epigastric pain 2, 8
• Elevated lactate dehydrogenase (LDH) indicates both hepatocellular damage and hemolysis 2
• The degree of liver enzyme elevation directly correlates with disease severity, with HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) representing the severe end of the spectrum 2, 8

Elevated Serum Creatinine (Renal Dysfunction)

Renal impairment results from glomerular endotheliosis—the pathognomonic lesion of preeclampsia—causing proteinuria and decreased glomerular filtration rate. 3, 1

• Glomerular endotheliosis consists of glomerular enlargement from hypertrophy of endothelial cells, a change seen in no other form of hypertension 3
• VEGF deficiency is central to this process, as VEGF normally maintains glomerular endothelial health and filtration barrier integrity 1
• Loss of VEGF signaling disrupts the glomerular filtration barrier, causing proteinuria 1, 7
• Decreased glomerular filtration rate occurs before and at the time of diagnosis, consistent with volume-expanded circulation 3, 1
• Reduced plasma volume develops from accelerated loss of protein from the vascular compartment 3

Pulmonary Edema

Pulmonary edema develops from increased pulmonary capillary permeability secondary to endothelial dysfunction, compounded by reduced plasma oncotic pressure from proteinuria and iatrogenic fluid overload. 8

• Generalized endothelial dysfunction increases pulmonary capillary permeability, allowing fluid extravasation into alveolar spaces 6, 7
• Reduced plasma volume paradoxically coexists with total body fluid overload due to third-spacing 3
• Loss of albumin through proteinuria decreases plasma oncotic pressure, favoring fluid shift into interstitial spaces 7
• Pulmonary edema is a severity criterion requiring immediate delivery consideration at any gestational age 8

Visual Disturbances

Visual symptoms result from cerebral edema, vasospasm, and ischemia affecting the occipital cortex and retinal vasculature. 2, 8

• Cerebral endothelial dysfunction causes vasogenic edema, particularly in the posterior circulation (posterior reversible encephalopathy syndrome pattern) 2, 8
• Retinal vasospasm and ischemia produce scotomas, blurred vision, and photophobia 8
• Severe cases may progress to cortical blindness from occipital lobe ischemia 7
• Visual disturbances indicate severe preeclampsia and mandate urgent evaluation for delivery 2, 8

Unifying Pathophysiologic Mechanisms

Vasoconstriction and Reduced Organ Perfusion

• Increased sensitivity to virtually all circulating pressor agents causes widespread vasoconstriction, though endogenous pressor levels are not elevated 3
• Reduced organ perfusion affects kidneys, liver, brain, and heart, with hemorrhage and necrosis occurring in severely affected organs 3, 1
• Cardiac involvement can produce subendocardial necrosis similar to hypovolemic shock 3

Coagulation Cascade Activation

• Although consumption sufficient for detection by standard testing occurs in only 10% of cases, sensitive markers of coagulation activation are present in most preeclamptic women 3
• Microthrombi formation further limits perfusion to end organs 3, 5

Angiogenic Imbalance as Central Mediator

• sFlt-1 acts as a decoy receptor, binding and neutralizing free VEGF and PlGF in maternal circulation 1, 4
• AT1 receptor autoantibodies (present in >95% of preeclamptic women) induce placental sFlt-1 production and correlate with disease severity 1
• The combined effect produces multi-organ maternal dysfunction affecting cardiovascular, renal, hepatic, cerebral, and hematologic systems 1, 9

Critical Clinical Pitfalls

• Do not assume that isolated findings represent mild disease; thrombocytopenia, elevated liver enzymes, rising creatinine, pulmonary edema, or visual disturbances each independently indicate severe preeclampsia requiring urgent delivery consideration 8
• Recognize that these manifestations can appear rapidly and progress within hours, necessitating frequent reassessment 8
• Understand that the severity of end-organ damage does not always correlate with blood pressure elevation; severe complications can occur with only moderately elevated pressures 7, 8
• Avoid attributing symptoms to other causes without first excluding preeclampsia in any pregnant woman beyond 20 weeks with new-onset hypertension 2, 8