What is the pathophysiology of varicose veins?

Pathophysiology of Varicose Veins

Varicose veins develop primarily from a loss of elasticity in the vein wall leading to valvular incompetence, rather than valves failing first—the weakened wall dilates, preventing valve leaflets from meeting properly, which then allows reversed blood flow and progressive venous hypertension. 1

Primary Mechanism: Vein Wall Weakness

• The fundamental defect involves genetic predisposition combined with weakened vascular walls and incompetent valves, creating a cascade of increased intravenous pressure 1, 2
• Research demonstrates that reduced vein wall elasticity and increased arterial inflow precede valvular incompetence, indicating the venous valves play a secondary role rather than being the primary cause 3
• The vein wall weakness appears to be the initiating factor—when the wall loses structural integrity, it dilates and the valve leaflets can no longer approximate properly 1

Structural and Molecular Changes

• Disruption of the normal arrangement of extracellular matrix (ECM) and smooth muscle cells creates the characteristic tortuous, dilated, serpentine appearance of varicose veins 4
• Alterations in ECM composition occur through varied expression of metalloproteinases and their inhibitors, which directly affects venous wall remodeling 4
• Biochemical and structural alterations of the vessel wall include extracellular matrix abnormalities and impaired balance between growth factors or cytokines 5
• Differential gene transcription influences the adaptive response of the venous wall to stimuli and the remodeling that leads to varicose vein development 4

Hemodynamic Consequences

• Once valves become incompetent, blood flows in reverse direction (distal to proximal becomes reversed) rather than the normal proximal flow pattern 1
• Failed valves allow blood to flow backward from deep to superficial veins instead of the normal superficial to deep direction 1
• Increased pressure on the affected venous system causes larger veins to become elongated and tortuous as the structural support fails 1
• Shear stress on venous endothelial cells from reversed or turbulent blood flow triggers inflammatory responses that perpetuate the disease 1

Contributing Factors

• Increased deep venous pressure arises from multiple sources including arteriovenous anastomoses, incompetent communicating (perforator) veins, or venous obstruction 6
• Primary valvular incompetence can result from venous thrombosis, thrombophlebitis, or congenital valvular agenesis 6
• Secondary valvular incompetence occurs from deep venous obstruction or increased venous distensibility, often related to circulating estrogens 6
• Ineffective function of the calf muscle pump fails to adequately propel blood proximally, contributing to venous stasis 5
• Changes in hydrostatic pressure, particularly with prolonged standing, exacerbate the underlying wall weakness 5

Clinical Implications

• The pathophysiology explains why symptoms worsen at the end of the day after prolonged standing—gravity and hydrostatic pressure maximally stress the weakened vein walls 2
• Symptoms improve with leg elevation because reducing hydrostatic pressure temporarily compensates for the structural wall defects 2
• Understanding that wall weakness precedes valve failure explains why treating junctional reflux is essential—addressing downstream tributaries alone leaves the upstream pressure source untreated 7