Venous reflux is the most consistent structural change observed in patients with CVI. Reflux commences in the superficial veins, and as the clinical class progresses, it extends to the perforator and the deep systems.

Reflux in the superficial venous system is the initial event in primary CVI. Venous ulcers are considered to be rare in patients with isolated superficial vein reflux, but 15.2–20 % of patients had isolated superficial vein incompetence only [16, 17]. Ulceration is commonly observed when reflux exists in both superficial and deep systems. Robertson et al. reported that in 43 % of patients with ulceration, there was combined superficial and deep vein reflux [4]. As already mentioned, CVI primarily and predominantly affects the superficial system [3].

Incompetent medial calf perforators are considered to be an important factor in the genesis of venous ulcer. They can produce a high pressure leak of blood from the deep to superficial vein during the contraction of the calf muscles producing ambulatory venous hypertension [18–20]. An incompetent calf perforator is considered significant, only when the calf muscle pump is defective or when there is pathology in the deep veins [21]. Objective findings of such pathological perforators include outward flow duration more than 500 ms and size equal to or more than 3.5 mm [22]. Incompetent perforators in a C2 class of patient revert to normal when the superficial reflux is eliminated.

Reflux in the deep veins, along with superficial and communicating vein incompetence, is a common finding in patients with venous ulcers (C6 class) [23–25]. Deep vein reflux is seen in less than 10 % in C2 class in comparison to 70 % in C6 class [3]. Two causes are suggested for reflux in the deep veins, the valve theory and the wall theory [26].

The valve theory suggests that reflux results from a thrombotic or nonthrombotic pathology. The most widely identified etiology for the damage and destruction of valves in the deep veins is post-thrombotic pathology. The nonthrombotic cause for deep vein valve failure was first identified and described by Robert Kistner. He coined the term primary vein valve incompetence (PVI) for this condition. In this condition, the valve cusps are stretched and elongated, floating freely in the vein lumen. The two cusps fail to meet and close in the midline, thus permitting reflux [23]. These changes are predominantly located in the proximal segments. Many etiological factors are suggested for this: wear and tear, phlebitis, connective tissue defects, etc. [26]. PVI can develop in the deep veins in discontinuous segments. The failure of deep vein valves may not happen in a sequential ascending or descending fashion [26].

The wall theory: The basic problem here is circumferential dilatation of the vein wall at the level of valve apparatus. The valve cusps are normally formed, but because of the increase in luminal circumference, they fail to meet across and close the vein lumen. Several factors are suggested for this defect. They include phlebitis and defect in the connective tissue framework [26].

Irrespective of the cause, reflux in deep veins impairs the lower limb venous return. In normal individuals, the calf muscle pump along with the competent valves ensures a streamlined, unidirectional cephalad flow in the deep veins. When there is reflux in the deep veins, this is converted into a bidirectional, turbulent, up and down movement – the “yo-yo” effect (Fig. 3.​5). The net effect is volume overload leading on to hypertension in the deep venous system. The perforator and superficial systems become incompetent secondary to this overload – the safety valve effect. The crucial factor in genesis of leg ulcer is the status of the popliteal vein valve. When this is competent, ulceration is rare even with extensive disease. On the other hand, incompetence of this valve results in ulceration. Hence, the popliteal valve is referred to as the gatekeeper [4]. Lim and colleagues have tried to define the precise clinical and hemodynamic significance of deep vein reflux (DVR) while controlling reflux in the superficial system. The study included 3,222 limbs in 2,349 patients using duplex ultrasound, CEAP classification, and venous filling index (VFI). According to them, DVR to the level of the knee and calf is associated with more severe disease irrespective of reflux in superficial veins [25].

Isolated involvement of a single system is extremely rare in clinical practice. According to Raju, multisystem multilevel reflux is more pathological than a single-system single-level reflux [24]. Our experience has been the same; 58 % of our patients had combined reflux in the superficial, perforator, and deep systems.

Reflux in the microvenous valves is now in the center stage. Till recently, it was believed that valves do not exist in veins <2 mm in diameter. This is now disproved. Reflux in the smaller venous tributaries is now recognized as an important factor in the pathogenesis of skin lesions in CVI. Microvenous valves can exist up to the sixth-generation tributaries with the third generation forming the boundary in pathological states. Failure of microvalves is shown to be a key factor for skin changes. Such changes can be present even in the absence of reflux within the GSV or its branches. Macro- and microvessel involvement when combined aggravates the severity of the lesions [27]. Sometimes even with extensive varices, some patients do not develop skin problems. This could be explained by the presence of competent microvalves especially in the third-generation boundary venules. These vessels are inaccessible for surgical intervention. There is robust evidence to show that foam sclerotherapy can obliterate them.

Nonthrombotic iliac vein lesion (NIVL) results from extraluminal compression of the left common iliac vein. The vein is compressed at its commencement by the right common iliac artery. This is a permissive lesion which requires another pathology such as trauma, cellulitis, edema, etc., to become clinically manifested. This condition is also known as May-Thurner syndrome and is being increasingly identified in a large number of CVD patients. The pathology can be totally corrected by endovenous stenting [28]. This is the only condition of primary CVI where obstruction of the deep vein is identifiable.

Structural changes in the calf muscles are identified in a number of patients with CVI. The clinical relevance of such findings is not properly understood. Significant functional impairment of the calf muscles was reported by Yang and his colleagues in 1999 [29]. Diminished calf muscle pump function is reported as a risk factor for ulceration in patients with varicose veins [4]. Biopsy and electron microscopic study of gastrocnemius muscle in patients with CVI has demonstrated several structural changes [30]. The changes correlated with ambulatory venous pressure (AVP) findings [30]. A recent study has reported increased calf muscle deoxygenation in patients with CVI [31]. It has been proposed that, rather than the calf muscle impairment resulting from CVI, the poor calf muscle itself may be responsible for pump failure in some patients with leg ulceration [4]. It has been reported that calf muscle pump function and dynamic calf muscle strength improved in a group of CVI patients after 6 months of structured exercise [32]. Such structured exercise program has been suggested as an adjuvant to mainstream treatment in patients with CVI [32].

The deep fascia of the leg has a major role in the calf muscle pump mechanism. Patients who have undergone emergency fasciotomy for traumatic conditions are reported to have impaired calf muscle pump function leading onto CVI [33]. Similar changes have been reported in a group of patients who have undergone elective fasciotomy for chronic exertional compartment syndrome [34].

Limitation of ankle joint movement is a risk factor for the development of ulcers in patients with varicose veins [4]. Two findings noted in patients with nonhealing venous ulcers are restricted movements at ankle joint and calf muscle wasting [35]. The relevance of ankle joint mobility on venous ulcer healing and calf muscle pump function has been emphasized by several workers [36–38] (Fig. 11.1).

Absorption of interstitial fluid and lymph is markedly disrupted adjacent to venous ulcer bed. Lymphatics were found to be absent in the ulcer bed and were present only sporadically in the intermediate zone [39].

The exact significance of these structural and functional alterations in the different locations is not fully understood. Whether they are the cause or the effect of CVI is also a debatable issue. It is well understood that these changes affect the calf muscle pump adversely and aggravate the venous hypertension setting in a vicious cycle. Correcting these changes would break the vicious cycle and improve the calf muscle function.