Risk Factors

Risk factors associated with CVI Include:

  • Age
  • Sex
  • A family history of varicose veins.
  • Obesity
  • Pregnancy
  • Phlebitis
  • Previous leg injury.
  • Standing and sitting for long periods of time.

Venous ulcers

  • The incidence of ulcers is 1% in the population. 20% of these develop venous ulcers. The prognosis of ulcers is poor with recurrence and delayed healing.
  • 50% of the venous ulcers need prolonged therapy lasting over 1 year.
  • The socioeconomic impact is dramatic with impaired ability to socialize thus reducing the quality of life and being a financial burden on the patient.
  • There is a loss of work productive hours which is over 2 million workdays/year.
  • The patient may take early retirement seen in 12.5% of the people with ulcers.
  • It is a tremendous burden on the health care system being over $ 3 billion annually.

Venous pathophysiology

Normal venous anatomy and function

The peripheral venous system is a reservoir and a conduit to return blood to the heart.

The proper functioning of the peripheral venous system depends on a series of muscle pumps and valves.
The blood in the lower limbs must return to the heart against the pull of gravity and against fluctuating those abdominal pressures to return to the heart while the patient is erect.

The veins of the lower limbs are either superficial or deep which are connected through a series of perforating veins.

The superficial veins are located above the muscle fascial plane. They are an interconnecting network which is the primary collecting system and return the blood to the deep system through multiple truncal veins. The main veins of the superficial system are the long and the short saphenous veins which run from the ankle and join the deeper veins – femoral vein in the groin (Sapheno-femoral junction) and the popliteal behind the knee (saphenopopliteal junction). Other superficial veins, including the posterior arch – lateral accessory saphenous and vein of Giacomini can also develop defects leading to CVI.

The deep venous system is located below the muscular fascia and is the collecting system and the outflow of the leg. This consists of the axial veins which follow the course of the major arteries in the leg and the intramuscular veins. Venous sinusoids within the leg muscles join to form the intramuscular venous plexi. Paired calf veins combine to form the large popliteal vein which passes through the adductor canal accompanying the artery and is called the superficial femoral vein. This is joined by the profound femoris vein and forms the common femoral vein. And continues as the external iliac vein.

The superficial veins are connected with the deep veins by perforating veins and pass through the anatomic fascial spaces.

A series of bicuspid valves are located in the superficial and the deep venous systems to see blood moved in the upward direction towards the heart against gravity pull and does nor reflux downwards. The first of these valves are located in the common femoral vein and rarely in the external iliac vein. The frequency of these valves increases from proximal to the distal part of the leg to prevent an increase in pressure at the ankles due to gravity pull. Perforating valves also contain valves in one direction, directing blood from the superficial to the deep.

The valves work in coherence with the muscles of the calf, thigh, and foot. Muscular contraction squeezes the delicate venous sinusoids forcing blood into the veins. The valve system makes sure the blood is forced in only an upward direction and not reversely. Soon after ambulation, the pressure in the leg veins is low (15-30 mmHg) because the muscles have emptied the venous system. Muscular relaxation then allows blood to fill the venous sinusoids via arterial flow through the superficial and deep venous systems.

In prolonged standing veins slowly fill and become distended making valves separate and increasing the pressure that is directly proportional to the height of the blood column. Contraction of the muscle pump empties the veins and reduce venous pressure.

  • Normal venous pressure. The standing venous pressure is 80 —90 mmHg. With exercise, the calf pressure drops to 20 – 30 mmHg (> 50% decrease). The return pressure is more gradual and takes > 20secs.
  • Abnormal pressure with deep vein reflux. The drop pressure with exercise is blunted (< 50% decrease). The return venous pressure to resting level is rapid because of a short refill time (< 20 sec).

Venous pathophysiology and dysfunction

  • Venous diseases occur when venous pressure is increased which impairs the return of blood through various mechanisms which include:
  • Valvular incompetence of the deep, superficial or perforator systems.
  • venous obstruction (DVT)
  • Combination of the above
  • Muscle pump dysfunction
  • These all produce venous hypertension on standing or ambulation. This disturbance in the microcirculation brings about changes in the microcirculation.
  • Prolonged venous hypertension may lead to hyperpigmentation, subcutaneous tissue fibrosis (lipodermatosclerosis)  and eventual ulceration.
  • In deep valve failure, normal blood volume is pumped out of the leg but refill occurs by both arterial flow and pathological retrograde flow. The venous pressure immediate after ambulation may be normal or elevated but veins refill quickly and high venous pressure occurs without muscle contraction. The valves are damaged mostly due to past DVT.
  • The incompetence of the valves may be a congenital primary defect due to weakness in the wall or valve leaflets or secondary to direct injury, superficial phlebitis of excessive venous distention due to hormonal effects or venous hypertension.
  • Failure of the valves located at the deep and superficial vein junctions as sapheno-femoral and saphenopopliteal junctions allows high pressure to be transmitted from the deep to the superficial venous systems resulting in varicose veins.
  • High pressure from the deep system can also be transmitted to the superficial system via the perforator valve incompetence. This is aggravated by the contraction of the muscle pump of the legs. The high pressure generated in the superficial veins results in valve incompetence. This is responsible for reflux in the superficial and deep venous systems.
  • Obstruction of the deep veins may result in rising in pressure with contraction of the muscles and secondary muscle pump dysfunction. The obstruction may occur due to the previous DVT with inadequate recanalization, venous stenosis or due to external compression (May-Thurner Syndrome with compression of the left common iliac vein as it passes between the right common iliac artery and the limbo-sacral region). Venous outflow obstruction is responsible for CVI.

May-Thurner syndrome

  • Dysfunction of the muscle pump prevents venous blood from being effectively emptied from the distal extremity. The muscle pump failure could occur as a primary disorder as in neuro-muscular conditions or muscle wasting syndromes or as a secondary disorder due to severe reflux or obstruction. In this, the post-ambulatory venous pressures will be nearly as high as the pressures after prolonged standing.
    Muscle pump dysfunction or failure is mainly responsible for superficial venous incompetence and its complication of stasis venous ulcer.
  • Changes in the hemodynamics of the large veins of the legs are transmitted to the venous microcirculation and finally develops venous microangiopathy. Features of this microangiopathy include – elongation, dilatation, tortuosity of the capillary beds, thickening of the basement membrane with increased collagen and elastic fibers, endothelial damage with a widening of the inter-endothelial spaces and increased peri-capillary edema with ‘halo’ formation.
  • The abnormal capillaries with increased permeability and high venous pressures lead to fluid accumulation, macromolecules, and extravasated RBCs into the interstitial spaces.
  • Besides changes in the blood vessels and connective tissue changes in the lymphatic network and nervous system occur.
  • Fragmentation and destruction of the micro lymphatics further impair drainage from the leg and dysfunction of the local nerve fibers may alter the regulatory mechanism.
  • Several mechanisms for the development of microangiopathy have been put forward and include fibrin cuff formation, growth factor trapping, and white blood cell trapping.
  • The fibrin cuff theory involves the accumulation of fluid containing fibrin into the pericapillary space. This cuff with impaired fibrinolysis increase the diffusion barrier inhibits the repair process and maintains the inflammatory process.
  • Another theory is the trapping of growth factor by fibrin and other macromolecules preventing the healing.
  • Another theory is the trapping of White blood cells in capillaries or post-capillary venules. The adhesion of the white cells with activation releases inflammatory mediators and proteolytic enzymes with endothelial damage which increases permeability or impedes flow leading to occlusion.

Clinical manifestation

  • CVI has a vast range of presentations form telangiectases to skin fibrosis and venous ulceration.
  • One must realize that the same presentations may be due to different problems like incompetent valves alone, venous obstruction alone, muscle pump dysfunction alone or in combination.
  • The major manifestations of CVI are dilated veins, edema, leg pain, and cutaneous changes.
  • Varicose veins are dilated veins that become progressively tortuous, larger and are prone to thrombophlebitis. Edema begins at the ankle and progresses up the leg and is worse on dependency. Pain and discomfort are worse on standing and relieved by elevation. The pain is due to the edema which increases the intra-compartmental pressure. Tenderness along the distended vein. Obstruction of the deep vein may give venous claudication of severe leg pain with ambulation.
  • Skin changes include hyperpigmentation due to hemosiderin deposition and eczematous dermatitis. Fibrosis may develop in the dermis and subcutaneous tissue (lipodermatosclerosis). There is an increased risk of cellulitis, leg ulceration and delayed wound healing.
  • Long-standing CVI may lead to lymphoedema.

Clinical classification of CVI

This is the CEAP classification: Clinical; Etiological; Anatomy; Pathophysiologic classification.

Clinically it has 7 categories (0 – 6) and further categorized by the presence or absence of symptoms.

Etiology is based on the congenital, primary and secondary causes of venous dysfunction.

Anatomic causes are superficial, deep and perforating veins

Pathophysiologic causes describe the underlying mechanism that causes CVI reflux, venous obstruction or both.