What is the pathophysiology of cor pulmonale?

Pathophysiology of Cor Pulmonale

Cor pulmonale develops when chronic pulmonary hypertension causes right ventricular hypertrophy and eventual failure through a cascade of vascular remodeling, hypoxic vasoconstriction, and ventricular interdependence mechanisms. 1, 2

Primary Vascular Mechanisms

The pathophysiology begins in the pulmonary vasculature through multiple interconnected mechanisms:

Hypoxic Pulmonary Vasoconstriction

• Chronic alveolar hypoxia triggers direct pulmonary vasoconstriction, the fundamental driver of increased pulmonary vascular resistance in cor pulmonale 1, 2
• This hypoxic response is a physiologic mechanism that becomes pathologic when sustained chronically 3
• Hypercarbia and acidosis further potentiate this vasoconstriction 3

Structural Vascular Remodeling

• Extensive remodeling affects all three layers of the pulmonary arterial walls: intimal thickening with proliferation of poorly differentiated smooth muscle cells, medial hypertrophy with abnormal extension of muscle to peripheral arteries (those accompanying alveolar ducts and alveoli), and adventitial thickening 3, 1
• Endothelial cell injury and intimal proliferation with deposition of elastic and collagen fibers progressively reduce the luminal cross-sectional area of the vascular bed 3, 1
• These structural changes increase wall stiffness and reduce the total cross-sectional area available for blood flow 3, 4

Vascular Bed Destruction

• In emphysematous lung disease, destruction of alveolar walls directly eliminates portions of the pulmonary vascular bed 1
• Since arteries accompany airways, there is a reduced number of intraacinar arteries in diseases affecting alveolar development 3
• Arteries coursing through scarred or fibrotic regions have further reduction in external diameter 3

Erythrocytosis Effects

• Chronic hypoxemia stimulates erythrocytosis, which increases blood viscosity and effective pulmonary vascular resistance 1

Hemodynamic Definition

Pulmonary hypertension—the hemodynamic basis of cor pulmonale—is defined as mean pulmonary arterial pressure ≥25 mmHg at rest by right heart catheterization (though recent guidelines suggest lowering this threshold to >20 mmHg) 2

• In cor pulmonale, the pulmonary hypertension is pre-capillary, characterized by mean pulmonary arterial pressure ≥25 mmHg with pulmonary wedge pressure ≤15 mmHg and pulmonary vascular resistance ≥3 Wood units 2
• In COPD (the most common cause), mean pulmonary artery pressure typically ranges between 20-35 mmHg in stable disease, though it worsens during exercise, sleep, and exacerbations 5
• A minority (<5%) of COPD patients develop "out-of-proportion" severe pulmonary hypertension with pressures >40 mmHg, which carries significantly higher mortality 1, 5

Right Ventricular Response and Failure Progression

The right ventricle undergoes a predictable sequence of changes when faced with chronic pressure overload:

Anatomic Vulnerability

• The right ventricle is anatomically designed to handle volume changes, not pressure loads, with a thin wall compared to the left ventricle 1
• When faced with increased pressure load, RV stroke volume decreases significantly more than the left ventricle would under similar pressure increases 1

Progression Sequence

The right ventricle responds through distinct phases 1, 2:

• Initial compensatory phase: Right ventricular hypertrophy develops as an adaptive response
• Development of isovolumic phases: Both contraction and relaxation phases become prolonged
• Progressive RV dilation: As compensation fails, the chamber dilates
• Eventual right ventricular failure: Decompensation occurs with clinical heart failure

Compromised Coronary Perfusion

• RV coronary perfusion becomes compromised through decreased perfusion pressure, elevated end-diastolic pressure, and potential subendocardial ischemia 1

Ventricular Interdependence

As the right ventricle dilates, it directly impairs left ventricular function through mechanical forces transmitted through the myocardium and pericardium 1:

• Mechanical flattening and leftward shift of the interventricular septum occurs 1
• Left ventricular end-diastolic pressure increases while transmural filling pressure decreases 1
• Left ventricular diastolic filling becomes impeded, reducing cardiac output 1

Additional Contributing Factors

Dynamic Hyperinflation

• Air trapping and dynamic hyperinflation in obstructive lung disease increase right atrial pressure and further compromise cardiac function, particularly during exercise 1

Hypoxemia Effects Beyond Vasoconstriction

Chronic hypoxemia contributes through multiple mechanisms 1:

• Direct stimulation of pulmonary vasoconstriction
• Increased ventilatory demand
• Stimulation of lactic acid production

Supplemental oxygen therapy can partially reverse these effects by decreasing pulmonary artery pressure, reducing respiratory rate and dynamic hyperinflation, and decreasing lactic acid production 1

Clinical Significance

• Only oxygen therapy produces specific vasodilation for pulmonary hypertension induced by hypoxic vasoconstriction; other vasodilators are limited by systemic effects 3
• Cor pulmonale is associated with higher mortality rates independent of other prognostic variables 2
• The condition represents the end result of chronic respiratory disease affecting lung structure and function, with COPD being the leading cause 2, 5