Causes of Pulmonary Edema
Pulmonary edema results from two fundamental mechanisms: cardiogenic causes (elevated cardiac filling pressures forcing fluid into alveoli) and non-cardiogenic causes (increased capillary permeability allowing fluid leak without elevated pressures).
Cardiogenic Pulmonary Edema
The primary mechanism is elevated left ventricular filling pressure causing increased pulmonary capillary wedge pressure, which drives fluid from the intravascular space into the pulmonary interstitium and alveoli 1, 2.
Cardiac Causes Leading to Elevated Pressures
Acute myocardial infarction or acute myocardial injury creates sudden ventricular dysfunction with inability to maintain forward flow, backing up pressure into the pulmonary circulation 1.
Decompensated heart failure from any cause (systolic or diastolic dysfunction) results in inadequate cardiac output with compensatory fluid retention and elevated filling pressures 1.
Valvular disease (particularly aortic stenosis and mitral regurgitation) creates pressure overload or volume overload that transmits backward into pulmonary veins 1.
Cardiomyopathy reduces myocardial functional reserve, and when combined with increased systemic vascular resistance, creates a mismatch that elevates left ventricular diastolic pressure 2, 3.
Cardiac arrhythmias (supraventricular tachycardia, complete heart block) impair ventricular filling or reduce cardiac output, leading to pulmonary congestion 1.
Pathophysiologic Mechanism
The Starling equation governs fluid movement: hydrostatic pressure gradients and oncotic pressure gradients across the capillary membrane determine net fluid flux 1. When pulmonary capillary hydrostatic pressure exceeds oncotic pressure (typically when pulmonary capillary wedge pressure exceeds 18-20 mmHg), fluid transudates into the interstitium 1. When lymphatic drainage capacity is overwhelmed, fluid accumulates in alveolar spaces 1.
Recent evidence suggests cardiogenic pulmonary edema often represents fluid redistribution rather than pure volume overload 2. Marked increases in systemic vascular resistance combined with insufficient myocardial reserve create a sudden pressure surge that shifts intravascular fluid into the lungs 2.
Barrier Disruption in Cardiogenic Edema
Prolonged elevation of capillary pressure causes breakdown of the alveolar-epithelial barrier through dysregulated inflammation, leukocyte infiltration, mechanical stretch, and reactive oxygen species 4, 5. This creates a mixed picture with both hydrostatic and permeability components 5. Patients with barrier disruption have elevated circulating surfactant protein B levels that persist after clinical improvement 5.
Non-Cardiogenic Pulmonary Edema
Increased Capillary Permeability
Sepsis and ARDS represent the prototypical non-cardiogenic causes, where inflammatory mediators (bradykinin, serotonin, prostaglandins) increase capillary permeability 1, 6.
The inflammatory process causes endothelial cell contraction, creating gaps that allow protein-rich fluid to leak into interstitium and alveoli 6.
In sepsis, variable degrees of capillary permeability allow oncotic molecules to cross freely, eliminating the protective oncotic gradient and promoting extravascular lung water accumulation 1.
Diffuse alveolar damage in ARDS progresses through exudative (days 1-5), fibroproliferative (days 6-10), and fibrotic phases (after 10 days) 1.
Other Non-Cardiogenic Causes
High-altitude pulmonary edema occurs from hypoxic pulmonary vasoconstriction creating uneven perfusion with capillary stress failure 3.
Neurogenic pulmonary edema results from massive sympathetic discharge causing systemic and pulmonary vasoconstriction 3.
Re-expansion pulmonary edema follows rapid lung re-expansion after pneumothorax or pleural effusion drainage 3.
Post-obstructive pulmonary edema develops after relief of upper airway obstruction from negative pressure generation 3.
Distinguishing Cardiogenic from Non-Cardiogenic
The critical clinical distinction requires assessment for elevated cardiac filling pressures versus normal pressures with increased permeability 1.
Echocardiography objectively assesses ventricular function, wall motion abnormalities, and valvular disease 1.
B-natriuretic peptide (BNP) or NT-proBNP elevation suggests cardiac etiology 1. However, obesity causes falsely low levels and renal failure causes falsely elevated levels 1.
Pulmonary artery catheterization definitively measures pulmonary capillary wedge pressure (>18 mmHg suggests cardiogenic; <18 mmHg suggests non-cardiogenic) 1, though this is reserved for cases not responding to therapy or with diagnostic uncertainty 1.
Chest radiograph patterns differ: cardiogenic typically shows cardiomegaly, cephalization, Kerley B lines, and perihilar distribution; non-cardiogenic shows normal heart size with diffuse bilateral infiltrates 1.
Clinical Pitfalls
Do not assume all pulmonary edema in heart failure patients is purely cardiogenic - prolonged elevated pressures cause barrier disruption creating a mixed picture 4, 5. Patients with cirrhosis, renal failure, or hypoalbuminemia develop edema from decreased oncotic pressure, which can affect both systemic and pulmonary circulation 1. Pulmonary hypertension from any cause (ARDS, chronic lung disease) elevates right heart pressures that can secondarily affect left heart filling 1.