The veins of the lower limbs can be subdivided into three subtypes: deep veins, superficial veins, and connecting veins (figure 1).

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1 VEIN DISEASE Vein disease may seem insignificant and harmless at first, but if left untreated, it can develop into a major problem. It occurs when veins have trouble transporting blood back to the heart and lungs. Vein disease affects approximately one-third of the population over the age of 45. While vein disease is progressive and irreversible, there are effective treatment and prevention options. This article reviews the circulatory system and the role of veins within this system. It explains some common vein problems and discusses the various treatment and prevention options. Circulatory System The circulatory system is a marvelous and precisely balances mechanism comprised of the heart, arteries, veins, and lymph vessels. It acts as a transporter of substances both to and from tissues and vital organs. Oxygen, nutrients, immune substances, hormones and chemicals necessary for the normal function of the body are transported via the arteries. Veins return oxygen-depleted blood back to the lungs where carbon dioxide is exchanged for oxygen. The circulatory system equalizes body temperature and assists in the maintenance of normal water and electrolyte balance. The average adult has a blood volume of approximately five litres. The circulatory system carries this quantity on one complete circuit through the body every minute. In 24 hours, 6800 litres of blood pass through the heart. Since veins tend to be larger and more numerous than arteries, the capacity of the venous system is greater than that of the arterial system. In fact, about 64% of the total circulating blood volume is within the venous system. Veins The veins of the lower limbs can be subdivided into three subtypes: deep veins, superficial veins, and connecting veins (figure 1). The central system of deep veins lies within skeletal muscles and other tissues and provides drainage from most of the muscle mass to the limbs. Ultimately, the deep veins connect with the veins of the abdomen. The superficial system includes the great saphenous vein and the small saphenous vein. The great saphenous vein is the longest vein in the body. It travels along the inside of the foot, leg and thigh where it joins the femoral deep vein. The small saphenous vein is shorter and travels along the lateral side of the foot, crosses the back of the leg and joins the deep vein behind the knee. The third major type is the connecting or perforating vein system, which connects the superficial and deep systems.

2 Vein Walls Vein walls differ from the walls of arteries in that they are highly distensible. This stretchability is a factor of the composition of the vein walls. The walls contain three distinct layers: adventitia (outer layer), media (middle layer) and intima (inner layer). Vein walls are relatively thin because the media is not well developed. The walls of veins primarily contain collagen and elastin fibers, whereas the arterial walls contain more smooth muscle tissue. Consequently, a vein is more easily compressed by adjacent muscles and bones. As we age, vein walls lose elasticity, causing them to stretch and dilate. Muscle Muscles play an important role in normal vein function through a process referred to as the venous pump. The muscles of the leg serve to lower vein pressure in dependent parts of the leg, relieve vein congestion in the same area and facilitate venous return both in times of rest and with more vigorous exercise. The massaging action of the muscle empties the deep veins and promotes blood flow from the superficial to the deep vein system. Valves

3 Since the veins in the legs are working against gravity, pumping blood upward from the feet to the heart, they contain valves to keep the blood flowing in the proper direction. Like swinging doors, these valves "float open" to allow the blood flow toward the heart, and "flap closed" again to prevent backflow toward the feet. Generally, the lower the vein is in the leg, the greater the number of valves within it. The loss of normal valve function in the veins results in abnormal blood flow. If the valve malfunctions because it has been damaged or because the vein walls are distended, blood pools in the veins. This dilates the vessel and further interferes with valve action. When an upper valve becomes defective, the fluid seeps into the next lower section of the vein. This doubles the weight the valve has to support and dilates the walls of the vessel. The results of blood flowing back down the leg can lead to bulging veins, swollen angles, and a feeling of heaviness and pain the legs. Blood can no longer be directed toward the deep vein. Valve failure and inactivity are precursors to venous insufficiency. Injury, disease, advanced age, excessive weight, pregnancy and heredity all contribute in varying degrees to possible valve malfunction. Types of Vein Disease Chronic venous insufficiency is the collective term used to describe a condition in which the return blood flow through the veins is impaired, resulting in elevated venous pressure. Once the vein walls or valves become weak or damaged, the walls can dilate. If the veins are continually stretched, over time the valves begin to malfunction. The combination of weakened valves and gravity can cause blood in the veins to flow back down into the legs. Vein disease is progressive in nature. If symptoms are left untreated, veins can become irreversibly damaged and unable to perform the pumping function they were designed to do. The vein walls become increasingly permeable, allowing blood to pool in surrounding leg tissue. Varicose Veins The term varicose comes from the Latin root varix, meaning "twisted". Varicose veins usually begin to appear between the ages of 30 and 70. For some people, they are simply a cosmetic concern; for others, varicose veins can cause a significant pain and discomfort, often leading to problems that are more serious. Varicose veins are typically swollen, twisted, blue in colour and close to the surface of the skin. They can be unsightly and uncomfortable. Veins often bulge, throb and feel heavy. the legs and feet can swell and the skin can itch. Varicose veins can occur in almost any part of the body. However, they are most often seen at the back of the calf or on the inside of the leg between the groin and ankle. Hemorrhoids (veins around the anus) can also become varicose. Women are more likely than men to develop varicose veins, partly because female hormones tend to relax the vein walls. Other contributing factors can include pregnancy, illness, injuring and excess body weight. Venous Ulcers In more advanced stages, varicose veins may develop into open sores around the ankle area. This occurs as a result of poor circulation in the ankle and a leakage of blood into the leg tissue. Skin organisms then attack the skin and cause active inflammation and infection. These open sores are often very difficult to heal, and, if left unattended, can be quite painful causing serious health problems. Deep Vein Thrombosis (DVT) Deep vein thrombosis refers to the process of forming, or the presence of, a blood clot in a deep vein such as those in the leg or pelvis.

4 Deep vein clots occur most often during long periods of inactivity such as bed rest following surgery or with an illness, or following trauma to an extremity. There is also an increased risk of thrombosis in women who are pregnant or who are using oral contraceptives, people with an inherited deficiency of certain anti-clotting factors and people with certain types of cancer. DVT commonly affects only a single leg and depending on the location, swelling and pain may be the chief symptom. The pain may worsen with increased activity or if standing still for a long period of time. Of significant concern with clots in veins is the risk that a portion of or the entire clot will become dislodged and travel through the bloodstream to the lung. This is called a pulmonary embolism and is a life-threatening complication that requires urgent treatment. Although some clots may never go away, they can be treated to prevent the clot from growing. The use of anticoagulant (blood thinner) medications may prevent this complication by decreasing the ability of the blood to clot. Facts increasing the Risk of Deep Vein Thrombosis Age > 40 years Major surgery Immobility Cardiopulmonary disease Obesity Hypercoagulation (cancer) Venous disease Warning Signs of Vein Disease Open sores or ulcers on lower legs Leg pain from prolonged sitting or standing Varicose or spider veins, especially during pregnancy Tingling, numbness, burning or cramping in legs and feet Discoloration of the skin Swollen ankles at night Family history of venous problems Tired heavy legs Treatment Options The best treatment for vein disease is early detection. While there is no known cure for vein disease, there are options ranging from self-help to surgery. Self-Help Options Avoiding Excess alcohol and smoking Wearing flat or low-heeled shoes to work calf muscles and prevent discomfort Maintaining normal weight to take unnecessary pressure off the veins Minimizing long periods of sitting or standing and changing your position to avoid pooling of blood in the lower limbs Avoiding tight clothing which can restrict circulation Elevating the legs to allow a greater gravitational downward flow of blood Avoiding direct sunlight to minimize vasodilation and swelling Exercising to improve blood circulation

5 Medical Compression Stockings Compression stockings are often the first line of defense in treating varicose veins or in slowing their progression. They provide "graduated" compression, with the greatest pressure at the ankle and diminishing pressure as the stocking goes up over the leg. The stockings support the weakened vein walls and help them perform the pumping action. They promote circulation and help limit gravity's downward pull. As a result, blood flow is increased and often there is a decrease in swelling, fatigue, and pain and a reduction in the risk of blood clot formation. Compression stockings should only be worn after consultation with a physician. The physician will indicate the desired compression ratio based on specific parameters. Proper fit is essential to ensure optimal efficacy. A professional fitter will measure various parts of the leg and foot using a precise fitting protocol. An improperly sized stocking negates the effect of graduated compression. Daily wearing of the garment is essential. The compression stocking should be put on first thing in the morning and taken off before going to bed. Compression stockings come in different fabric weights, styles and colours. Compression stockings should not be confused with other types of stockings such as support hose and anti-embolism stockings. Support hose offer light, non-medical compression, which may help the legs feel better, but they cannot provide sufficient compression to prevent the progression of vein disease. Anti-embolism stockings (sometimes referred to as TEDs) are generally reserved for hospital use. They are used for managing post surgical patients at risk of developing a clot, and are specifically designed for people who are bedridden. Surgery If varicose veins do not respond to life-style adjustments, or if they are more severe, surgery may be recommended. There are various surgical treatment options available. Sclerotherapy is an outpatient procedure that involves injecting small and medium-sized varicose veins with a solution that scars the affected veins. The scarring effectively closes the veins and forces the blood to reroute to healthier veins. Ambulatory phlebectomy is an outpatient procedure involving the removal of smaller varicose veins through a series of tiny skin punctures. The procedure is frequently preformed under a local anesthetic and scarring is generally minimal. Vein stripping entails removal of a long vein through small incisions. For most people, this is also an

6 outpatient procedure and normal activities can usually be resumed within 2 weeks of the procedure. Endoscopic vein surgery is usually considered only in advanced cases of vein disease involving leg ulcers. Surgeons use a thin video camera inserted in the leg to visualize and treat the affected veins. PHARMAwise is authored and published by Dawn M. Frail, B.Sc. (Pharm), M.Sc. and made possible through the support of the Pharmacy & Apotex Continuing Education (PACE) program, the Apotex Advisory Board and your pharmacist. Reference to articles contained in this infoletter are available by contacting the Apotex Professional Affairs Department at , extension PHARMAwise is intended to provide drug and health information to care providers. The publisher, sponsor, and distributor are not responsible for losses arising from the use of information in this publication.

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