What are the cardiogenic and non‑cardiogenic causes of pulmonary edema?

Pulmonary Edema Causes

Pulmonary edema results from either elevated pulmonary capillary hydrostatic pressure (cardiogenic) or increased capillary membrane permeability (non-cardiogenic), with the critical distinction requiring assessment of cardiac filling pressures and structural cardiac abnormalities. 1

Cardiogenic Causes

Cardiogenic pulmonary edema develops when left-sided heart dysfunction elevates pulmonary capillary wedge pressure above plasma oncotic pressure (typically >18 mmHg), driving fluid transudation into the pulmonary interstitium and alveoli. 1, 2

Primary cardiac etiologies include:

• Acute myocardial infarction or injury creates sudden ventricular dysfunction with elevated left ventricular filling pressure and increased pulmonary capillary wedge pressure 1
• Decompensated heart failure from any cause results in inadequate cardiac output with compensatory fluid retention and elevated filling pressures 1
• Valvular disease, particularly aortic stenosis and mitral regurgitation, creates pressure or volume overload that transmits backward into pulmonary veins 1
• Cardiomyopathy of any etiology increases capillary hydrostatic pressure through impaired ventricular function 1
• Pericardial disease restricts cardiac filling and elevates venous pressures 1
• Cardiac arrhythmias such as supraventricular tachycardia impair ventricular filling or reduce cardiac output, leading to pulmonary congestion 1

Contributing systemic factors:

• Renal failure increases capillary hydrostatic pressure through volume overload 1
• Cirrhosis with portal hypertension elevates hydrostatic pressure 3, 1

The pathophysiologic mechanism follows the Starling equation, where hydrostatic pressure gradients and oncotic pressure gradients across the capillary membrane determine net fluid flux. 1, 2 When pulmonary capillary hydrostatic pressure exceeds oncotic pressure, fluid transudates into the interstitium. 1

Non-Cardiogenic Causes

Non-cardiogenic pulmonary edema occurs when inflammatory mediators increase capillary permeability despite normal or low cardiac filling pressures (<18 mmHg PCWP). 1 The inflammatory process causes endothelial cell contraction, creating gaps that allow protein-rich fluid to leak into interstitium and alveoli. 1

Primary non-cardiogenic etiologies:

• Sepsis and ARDS represent prototypical causes where inflammatory mediators increase capillary permeability 1
• Diffuse alveolar damage in ARDS progresses through exudative, fibroproliferative, and fibrotic phases 1
• High-altitude exposure causes pulmonary edema in 40-60% of mountaineers through mechanisms including subclinical edema and increased cough-receptor sensitivity 1
• Pulmonary embolism causes cough and edema in nearly half of documented cases 1
• Diabetic ketoacidosis can cause noncardiogenic pulmonary edema through reduction in colloid osmotic pressure that increases lung water content and decreases lung compliance 3

Iatrogenic factors:

• Excessive fluid administration, blood product transfusions, and injurious mechanical ventilation aggravate existing lung injury 1

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 This creates protein-rich edema fluid with an edematous fluid/plasma protein ratio greater than 0.7. 4

Distinguishing Cardiogenic from Non-Cardiogenic

The critical clinical distinction requires assessment for elevated cardiac filling pressures versus normal pressures with increased permeability. 1

Diagnostic approach:

• Echocardiography objectively assesses ventricular function, wall motion abnormalities, and valvular disease to identify structural/functional cardiac abnormalities 3, 1
• B-natriuretic peptide (BNP >35 pg/mL ambulatory, >100 pg/mL hospitalized) or NT-proBNP (>125 pg/mL ambulatory, >300 pg/mL hospitalized) elevation suggests cardiac etiology, though obesity and renal failure can affect levels 3, 1
• Pulmonary artery catheterization definitively measures pulmonary capillary wedge pressure: values >18 mmHg suggest cardiogenic, <18 mmHg suggest non-cardiogenic 1

Common pitfall: The Universal Definition of Heart Failure requires symptoms/signs caused by structural/functional cardiac abnormalities AND either elevated natriuretic peptides OR objective evidence of cardiogenic pulmonary or systemic congestion. 3 In HFpEF specifically, natriuretic peptide levels are lower relative to HFrEF for given elevations in left ventricular end-diastolic pressure, and higher BMI (prevalent in HFpEF) can suppress levels. 3

The differential diagnosis of dyspnea must systematically exclude cardiac, pulmonary, and other sources before assigning the diagnosis. 3 For edema, first differentiate true edema from lymphedema using the Stemmer sign (inability to lift skin fold at base of second toe suggests lymphedema), though obesity may cause false-positives. 3