Peripheral artery disease (PAD) and peripheral venous disease (PVD) have a lot in common.

Both are conditions that involve the vascular (or circulatory) system and affect the blood vessels
in areas outside your heart. That means they are both types of peripheral vascular disease.

Blood vessels -- arteries and veins -- are tube-like structures that allow blood, oxygen, and
waste to travel through your body. When arteries don’t work properly, your feet and legs can’t
get enough oxygen and other needed supplies, like nutrients. And when veins aren’t working,
there can be a buildup of blood materials, like fluid, in your limbs.

● PAD means you have narrowed or blocked arteries -- the vessels that carry
oxygen-rich blood as it moves away from your heart to other parts of your body.
● PVD, on the other hand, refers to problems with veins -- the vessels that bring your
blood back to your heart.

1. FUNCTIONAL - not related to structural problems in blood vessel walls. Instead

this can stem from vessel spasm or compression

- Your vessels naturally widen and narrow in response to your environment.

But in functional PVD, your vessels exaggerate their response.
E.G. Raynaud’s disease, when stress and temperatures affect your
blood flow.

- The most common causes of functional PVD are:

- emotional stress
- cold temperatures
- operating vibrating machinery or tools
- drugs

2. ORGANIC - associated with vessel blockage due to fatty infiltrates, inflammation,

or tissue damage.

- Organic PVD means there’s change in the structure of your blood

vessels. For example, the plaque buildup from atherosclerosis can
cause your blood vessels to narrow.

- The primary causes of organic PVD are:

- Smoking
- high blood pressure
- Diabetes
- high cholesterol
- Additional causes of organic PVD include extreme injuries, muscles or
ligaments with abnormal structures, blood vessel inflammation, and
infection.
What Causes PAD and PVD?

PAD:
➔ Most often PAD happens because of atherosclerosis, when plaque, cholesterol, and
other substances build up within an artery’s wall and make it narrower inside. If enough
plaque builds up, it can block blood flow inside the artery. (Blood clots can also get in the
way of the flow.) Like PVD , there also seems to be a genetic component to PAD. When
the blood is blocked it lowers the amount of oxygen and nutrients that get to your limbs.
This can create lasting damage to your skin, nerves, and muscle tissue.
➔ Less-common causes of PAD include injuries to the arteries, unusually shaped muscles
or ligaments, and infections.

PVD:
➔ PVD has several different forms. With chronic venous insufficiency, the valves in your
veins allow blood to flow backwards in the wrong direction. This can create pressure and
strain that damage the tissues causing bulging of your veins, especially if you are
pregnant, overweight, or tend to sit or stand in one position for a long time. On the milder
end, this condition can lead to spider veins -- small, raised, swollen blood vessels that
twist and turn. As the problem becomes more severe, it can become painful and lead to
varicose veins, which are larger but not life-threatening.

ANATOMY:
The peripheral vascular system (PVS) includes all the blood vessels that exist outside the heart.
The peripheral vascular system is classified as follows: The aorta and its branches:

The arterioles
The capillaries
The venules and veins returning blood to the heart
The function and structure of each segment of the peripheral vascular system vary depending
on the organ it supplies. Aside from capillaries, blood vessels are all made of three layers:

- The adventitia or outer layer which provides structural support and shape to the vessel
- The tunica media or a middle layer composed of elastic and muscular tissue which
regulates the internal diameter of the vessel
- The tunica intima or an inner layer consisting of an endothelial lining which provides a
frictionless pathway for the movement of blood

Within each layer, the amount of muscle and collagen fibrils varies, depending on the size and
location of the vessel.

Arteries
Arteries play a major role in nourishing organs with blood and nutrients. Arteries are always
under high pressure. To accommodate this stress, they have an abundance of elastic tissue and
less smooth muscle. The presence of elastin in the large blood vessels enables these vessels to
increase in size and alter their diameter. When an artery reaches a particular organ, it
undergoes a further division into smaller vessels that have more smooth muscle and less elastic
tissue. As the diameter of the blood vessels decreases, the velocity of blood flow also
diminishes. Estimates are that about 10% to 15% of the total blood volume is contained in the
arterial system. This feature of high systemic pressure and low volume is typical of the arterial
system.

There are two main types of arteries found in the body: (1) the elastic arteries, and (2) the
muscular arteries. Muscular arteries include the anatomically named arteries like the brachial
artery, the radial artery, and the femoral artery, for example. Muscular arteries contain more
smooth muscle cells in the tunica media layer than the elastic arteries. Elastic arteries are those
nearest the heart (aorta and pulmonary arteries) that contain much more elastic tissue in the
tunica media than muscular arteries. This feature of the elastic arteries allows them to maintain
a relatively constant pressure gradient despite the constant pumping action of the heart.

Arterioles

Arterioles provide blood to the organs and are chiefly composed of smooth muscle. The
autonomic nervous system influences the diameter and shape of arterioles. They respond to the
tissue's need for more nutrients/oxygen. Arterioles play a significant role in the systemic
vascular resistance because of the lack of significant elastic tissue in the walls.

The arterioles vary from 8 to 60 micrometers. The arterioles further subdivide into
meta-arterioles.

Capillaries

Capillaries are thin-walled vessels composed of a single endothelial layer. Because of the thin
walls of the capillary, the exchange of nutrients and metabolites occurs primarily via diffusion.
The arteriolar lumen regulates the flow of blood through the capillaries.

Venules

Venules are the smallest veins and receive blood from capillaries. They also play a role in the
exchange of oxygen and nutrients for water products. There are post-capillary sphincters
located between the capillaries and venules. The venule is very thin-walled and easily prone to
rupture with excessive volume.

Veins
Blood flows from venules into larger veins. Just like the arterial system, three layers make up
the vein walls. But unlike the arteries, the venous pressure is low. Veins are thin-walled and are
less elastic. This feature permits the veins to hold a very high percentage of the blood in
circulation. The venous system can accommodate a large volume of blood at relatively low
pressures, a feature termed high capacitance. At any point in time, nearly three-fourths of the
circulating blood volume is contained in the venous system. One can also find one-way valves
inside veins that allow for blood flow, toward the heart, in a forward direction. Muscle
contractions aid the blood flow in the leg veins. The forward blood flow from the lower
extremities to the heart is also influenced by respiratory changes that affect pressure gradients
in the abdomen and chest cavity. This pressure differential is highest during deep inspiration,
but a small pressure differential is observable during the entire respiratory cycle.

Structure and Function

Vessels transport nutrients to organs/tissues and to transport wastes away from organs/tissues
in the blood. A primary purpose and significant role of the vasculature is its participation in
oxygenating the body.[1] Deoxygenated blood from the peripheral veins is transported back to
the heart from capillaries, to venules, to veins, to the right side of the heart, and then to the
lungs. Oxygenated blood from the lungs is transported to the left side of the heart into the aorta,
then to arteries, arterioles, and finally capillaries where the exchange of nutrients occurs.
Loading and unloading of oxygen and nutrients occur mostly in the capillaries.

PATHOPHYSIO:
➔ Atherosclerosis begins with lipoprotein accumulation within the intimal layer of large
arteries. The lipoprotein presence within the endothelium leads to lipid oxidation and
cytokine response with the infiltration of lymphocytes and macrophages. Macrophages
consume these oxidized lipids and form foam cells leading to the development of "fatty
streaks”. These fatty streaks can eventually develop into more advanced plaques
consisting of necrotic lipid cores and smooth muscle cells (SMC). SMC and endothelial
cells secrete cytokines and growth factors, leading to migration of SMC to the luminal
side of the plaque and extracellular matrix synthesis (a suspension of
macromolecules that supports everything from local tissue growth to the maintenance of
an entire organ.). And eventual formation of a fibrous plaque. Fibrous plaque stability
is principally dependent on its composition with more vulnerable plaques consisting
of a thinner fibrous cap and more numerous inflammatory cells.

➔ Atherosclerotic plaque builds up slowly over decades within the wall of the vessel.
Plaque accumulation results in vascular stenosis (narrowing of bv) and frequent
vascular dilation (term for when blood vessels in your body widen, allowing more blood
to flow through them and lowering your blood pressure. ) to maximize end-organ
perfusion (Perfusion is the passage of fluid through the circulatory system or lymphatic
system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed
in tissue.). Once the vessel dilation capacity is maximized, the plaque continues to
accumulate, which further compromises the lumen occasionally, leading to critical
 narrowing of the artery. As narrowing progresses and obstructs the artery, collateral
circulatory beds frequently develop to preserve distal perfusion and tissue viability.
These collateral circulatory pathways are unable to match the blood supply provided by
a healthy vessel completely. IC (Inhibition of vascular IC is associated with increased
atherosclerotic burden and plaque instability. IC protects against atherosclerosis by
inhibiting T-cell activity and cytokine production, promoting regulatory T-cell
differentiation and inducing T-cell exhaustion.) results when blood flow distal to the
occlusion is sufficiently compromised, resulting in fixed oxygen delivery that is unable
to match oxygen demand. The most severe form of PAD is critical limb ischemia, which
is defined as limb pain at rest or impending limb loss.

LIPOPROTEIN ACCUMULATION ➡ LIPID OXIDATION AND CYTOKINE RESPONSE

➡ DEVELOPMENT OF “FATTY STREAKS” ➡ VASCULAR STENOSIS AND
FREQUENT VASCULAR DILATION ➡ CRITICAL NARROWING OF THE ARTERY ➡
DECREASED BLOOD FLOW ➡ DEPRIVATION OF OXYGEN AND NUTRIENTS ➡
PAIN

➔ Other Diseases of PAD:

● Buerger’s Disease
- Buerger’s disease is related to smoking. The disease causes swelling of
the small and medium-sized arteries (and sometimes the veins) in your
feet and legs. This rare disorder, which causes the peripheral vessels to
tighten or constrict, is more common in men, especially smokers aged
20 to 40. Smoking causes the blood vessels to tighten in everyone
who smokes. But in people with Buerger’s disease, there is so much
tightening in the vessels that a lack of oxygen to the cells (ischemia) or
tissue death (necrosis) may result. The symptoms may be different for
everyone, but the condition most often causes tender, swollen areas over
the vessels, followed by coldness of the feet and hands. Pain in the
legs during walking (called intermittent claudication) may happen because
of an arterial blockage. The most serious cases sometimes cause the
tissue to die, and amputation of the fingers and toes may be needed.
People with Buerger’s disease must stop smoking completely, and
circulation usually improves soon after.

● Raynaud’s Phenomenon
- Raynaud’s phenomenon happens more often in women. It is a
circulation disorder that causes the arteries in the fingers and toes to
tighten or spasm when they are exposed to cold temperatures,
smoking, or emotional stress. Often, the cause of Raynaud’s
phenomenon is not known. Sometimes, it is a side effect of other
conditions, such as connective tissue disease, trauma, or diseases of the
glands or central nervous system. People with the disorder may feel
 numbness or tingling in their fingers and toes. They may also notice that
their skin turns pale or blue, followed by reddening in the affected areas.
Attacks may last from a few minutes to several hours and are usually
treated with gradual warming of the fingers and toes to restore blood flow.
Therapy may also include pain relievers, calcium channel blockers,
quitting smoking, and avoiding cold temperatures and emotional upset.

➔ Chronic venous insufficiency is either due to reflux (backward flow) or obstruction

of venous blood flow. Chronic venous insufficiency can develop from the protracted
valvular incompetence of superficial veins, deep veins or perforating veins that
connect them. In all cases, the result is venous hypertension of the lower extremities.

➔ Superficial incompetence is usually due to weakened or abnormally shaped valves or

widened venous diameter which prevents normal valve congruence. The leaky valve in
most cases is located near the termination of the greater saphenous vein into the
common femoral vein. While in some cases the valve dysfunction may be congenital, it
can also be a result of trauma, prolonged standing, hormonal changes or thrombosis.

➔ Deep vein dysfunction is usually owing to the previous DVT which results in
inflammation, valve scarring and adhesion, and luminal narrowing. Perforating vein
valvular failure allows higher pressure to enter the superficial venous system. The
subsequent dilation prevents the proper closure of the valve cusps in the superficial
veins. Most patients will also have the disease in the superficial veins. The resting
venous pressure is a summation of the outflow obstruction, capillary inflow, valve
function, and muscle pump function.

➔ Regardless of the cause, the persistently elevated venous hydrostatic pressure may
result in lower extremity pain, edema, and venous microangiopathy. Some patients
develop permanent skin hyperpigmentation from hemosiderin deposition as red blood
cells extravasate into the surrounding tissue. Many of these patients will also have
lipodermatosclerosis, which is skin thickening from fibrosis of subcutaneous fat. As the
disease progresses, the perturbed microcirculation and dermal weakening can result in
ulcer formation.

MALFUNCTIONS OF THE VALVES ➡ DECREASE VENOUS RETURN ➡ VENOUS

HYPERTENSION ➡ CIRCULATORY STASIS ➡ TISSUE HYPOXIA ➡
INFLAMMATION ➡ NECROSIS

➔ Other Diseases of PVD:

● Venous blood clots (including deep vein thrombosis or DVT)
- It occurs when a blood clot (thrombus) forms in one or more of the
deep veins in the body, usually in the legs. Deep vein thrombosis can
 cause leg pain or swelling. Sometimes there are no noticeable symptoms.
When the clot develops in a vein deep within the leg, it is called deep
vein thrombosis (DVT). The condition can be life threatening if the clot
breaks loose from the vein and travels to the lungs, where it can
completely block blood flow.

● Pulmonary embolism
- Pulmonary embolism is caused by a blood clot (pulmonary embolus) that
breaks loose from where it formed in a vein and travels to your lungs.

● Phlebitis
- There are two forms of phlebitis. The most common form is swelling of a
vein near the skin’s surface, usually in the leg. This is called superficial
phlebitis. Swelling of the veins inside the leg is less common but more
serious. This is called deep phlebitis.
- For superficial phlebitis, the area looks reddish and feels painful.
The pain of this condition can usually be treated with moist heat, aspirin,
or anti-inflammatory medicines.
- The more dangerous form of phlebitis, deep phlebitis, usually causes
greater pain. This type of phlebitis is more likely to lead to blood clots
in the veins and a possible blood clot in the lungs (pulmonary
embolus).

● Varicose veins
- Varicose veins are swollen, purple veins in the legs that are visible
under your skin. They are caused by damage to blood vessels close to
the surface of your skin, slowed blood flow, or the damage or absence
of normal valves in your veins.
- Normally, blood flow in the veins is aided by valves, which keep the blood
moving upward, against the force of gravity. If these valves are weak or
blood flows slowly in the veins, the blood may pool and cause the veins to
bulge. Varicose veins are more common in women than in men. The
condition also runs in families. Pregnant women may get varicose veins
because of hormonal changes and the extra pressure that the baby puts
on the lower-stomach area. Varicose veins may also be caused by being
severely overweight or by standing for long periods.

PROGNOSIS:
➔ The overall prognosis of patients with the peripheral vascular disease must take
into account patient risk factors, cardiovascular health, and disease severity. In
terms of limb health at 5 years, nearly 80% of patients will have stable
claudication symptoms. Only 1% to 2% of patients will progress to critical limb
 ischemia in 5 years. 20% to 30% of patients with PAD will die within 5 years, with
75% of those deaths attributed to cardiovascular causes.

MANAGEMENT:
EXERCISE:
➔ Intermittent claudication is a cardinal symptom in patients with PAD. The classic
manifestation is muscle discomfort (patients may complain of muscle fatigue,
aching, or persistent cramp-like pain) in the lower limb reproducibly produced by
exercise and relieved by short-term rest.

➔ PAD is caused by stenotic or occlusive atherosclerotic lesions in the major

arteries supplying the lower extremities. Patients with intermittent claudication
have normal blood flow at rest. With exercise, stenotic/occlusive lesions in the
arterial supply of the leg muscles limit the increase in blood flow, causing a
mismatch between oxygen supply and the metabolic demand of the muscle [1].
Patients with PAD shift more quickly to anaerobic metabolism, a less efficient
means of energy production, during exercise, and have elevated lactate levels
even at rest [6]. Acquired metabolic abnormalities of the muscles of the lower
extremity also contribute to the reduced exercise performance and capacity of
patients with PAD [2,6].

➔ Claudication significantly affects quality of life and is associated with severe

functional impairment that can be significantly improved by exercise intervention
in properly selected patients [6].
➔ The treatment of limb symptoms and exercise limitation should initially focus on
structured, supervised exercise before any attempts are made to revascularize
patients with claudication. A considerable body of evidence supports the clinical
benefits of a supervised exercise program in improving exercise performance
and quality of life [7].
➔ The fundamental component of training is a supervised program of treadmill
exercise [5]. The exercise session begins with treadmill exercise at a speed and
grade that induce claudication within 3 to 5 minutes. The patient is instructed to
stop walking and rest when his or her claudication pain reaches a moderate level.
When the claudication has abated, the patient resumes walking until moderate
claudication discomfort recurs. This cycle of exercise and rest is repeated for at
least 30 minutes in the first few sessions of the program. In subsequent visits, the
speed or grade of the treadmill is increased if the patient is able to walk for 10
minutes or longer at a lower workload without reaching moderate claudication
pain.
➔ The duration and frequency of the exercise training sessions and duration of the
exercise training program are important to achieve maximal benefit with training
sessions: >30 minutes per session provides greater benefit than <30 minutes per
session; >3 sessions per week is more effective than <3 sessions per week, and
 program lengths of >26 weeks are more effective than program lengths of <26
weeks [9].

➔ Alternatives to treadmill exercise potentially consist of various forms of lower

extremity exercise alone or in combination (brisk walking, bicycle ergometer, and
strength training). However, the outcomes of treadmill exercise have so far been
found to be superior to the outcomes of several other lower extremity exercises,
namely cycling, stair climbing, and static and dynamic leg exercises [10].

➔ While home exercise (unsupervised) programs can be modified or supplemented

to improve their effectiveness, structured, supervised exercise programs
generally have superior outcomes compared to unsupervised programs. A few
studies have demonstrated that patients completing home-based exercise
programs were able to improve both their initial claudication distance and
absolute claudication distance [11,12].