Peripheral Artery Disease

Epidemiology and Etiology

Epidemiology

• Affects approximately 10% of the population > 55 years of age in the United States
• Worldwide prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is 3%–12%
• Men > women
• Higher prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency among African Americans and non-Hispanic Whites
• Lower rates in Hispanics and Asians

Etiology

Peripheral artery disease (PAD) usually has the same causative factors as coronary and carotid disease.

• Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis:
  • Aging
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases and tobacco use
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
  • Hypercholesterolemia Hypercholesterolemia A condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population. Lipid Disorders
  • Hyperhomocysteinemia
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
• Arterial embolism:
  • Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism atheroembolism Atheroembolism An embolus is an intravascular solid, liquid, or gaseous material that is carried by the blood to a site distant from its point of origin. Emboli of all types warrant immediate medical attention. The majority of emboli dislodge from a thrombus, forming a thromboembolus. Other less common nonthrombotic types of emboli are cholesterol, fat, air, amniotic fluid, and tumor emboli. Nonthrombotic Embolism
  • Atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
  • Artificial heart valves
• Functional:
  • Vasospasm
  • Previous injury to the limb
• Risk groups:
  • Age ≥ 70 years
  • Age 50–69 years + smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases or diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Age 40–49 + diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus + 1 other risk factor for atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis
  • Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis at other sites (e.g., coronary, carotid, renal)

Pathophysiology

• Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis: endothelial cell dysfunction → macrophage and cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism accumulation → foam cell formation → platelet-derived growth factor Platelet-derived growth factor Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. Hypertrophic and Keloid Scars (PDGF) and fibroblast growth factor Fibroblast growth factor A family of small polypeptide growth factors that share several common features including a strong affinity for heparin, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family. X-linked Hypophosphatemic Rickets (FGF) release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology  → smooth muscle cell migration → proliferation and extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars deposition → fibrous Fibrous Fibrocystic Change plaque Plaque Primary Skin Lesions
• Subintimal accumulation of lipid and fibrous Fibrous Fibrocystic Change material of the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology → vessel lumen narrowing → restricted blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure → chronic ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage of the affected limb
• Plaque Plaque Primary Skin Lesions rupture or thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus → abrupt occlusion of downstream vessels → acute ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage of the limb

Clinical Presentation

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with PAD may be asymptomatic (20%–25%) or present with evidence of chronic or acute limb ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage.

Chronic arterial insufficiency

• Symptoms:
  • The lower extremities are most commonly affected.
  • Intermittent claudication Intermittent claudication A symptom complex characterized by pain and weakness in skeletal muscle group associated with exercise, such as leg pain and weakness brought on by walking. Such muscle limpness disappears after a brief rest and is often relates to arterial stenosis; muscle ischemia; and accumulation of lactate. Thromboangiitis Obliterans (Buerger’s Disease): 
    • Reproducible, painful cramping in the buttock, hips, thighs, calf, or foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy with exertion 
    • Relieved with rest
  • Atypical limb pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or feeling of “heaviness”
  • Limb numbness or weakness
  • Impotence, erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction
• Physical exam findings:
  • Poorly healing wounds
  • Discoloration:
    • Pale with limb elevation
    • Redness Redness Inflammation when limb is lowered
    • Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination
  • Weak or absent pulse below a narrowed area of the artery
  • Bruits over arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology heard on auscultation
  • Decreased blood pressure in the affected limb
  • Severe disease: 
    • Loss of hair follicles, sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess, and sebaceous glands 
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions becomes smooth and shiny.
• Fontaine classification:
  • Used to determine the severity of PAD
  • Stages are based on symptoms and exam (see table).

Chronic limb-threatening (critical) ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage

Any 1 of the following indicates that blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure no longer meets the metabolic demands of the limb tissues at rest:

• Resting pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
  • Worse distally
  • Aggravated by limb elevation
• Ulcer
• Gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction

Acute limb ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage

Acute limb ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage is most commonly due to an embolism or plaque Plaque Primary Skin Lesions rupture. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will demonstrate acute onset of:

• 6 Ps PS Invasive Mechanical Ventilation: 
  1. Pain
  2. Pallor 
  3. Pulseless 
  4. Poikilothermia (cold)
  5. Paresthesia 
  6. Paralysis
• Blue toe syndrome:
  • Due to cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism atheroembolism Atheroembolism An embolus is an intravascular solid, liquid, or gaseous material that is carried by the blood to a site distant from its point of origin. Emboli of all types warrant immediate medical attention. The majority of emboli dislodge from a thrombus, forming a thromboembolus. Other less common nonthrombotic types of emboli are cholesterol, fat, air, amniotic fluid, and tumor emboli. Nonthrombotic Embolism to digital arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
  • Pedal pulses will be normal.
• Ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers or gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction
• Ankle blood pressure ≤ 50 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg

Diagnosis

Diagnostic algorithm for PAD

This algorithm demonstrates the diagnostic pathway for a patient presenting with signs or symptoms of PAD:

The diagnosis is usually established through clinical history, exam, and non-invasive testing techniques ( ankle-brachial index Ankle-brachial index Comparison of the blood pressure between the brachial artery and the posterior tibial artery. It is a predictor of peripheral arterial disease. Cardiovascular Examination (ABI), exercise testing).

Note that those with features of limb-threatening ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage need urgent vascular surgery Vascular surgery Vascular surgery is the specialized field of medicine that focuses on the surgical management of the pathologies of the peripheral circulation. The main goal of most vascular procedures is to restore circulatory function to the affected vessels by relieving occlusions or by redirecting blood flow (e.g., bypass). Vascular Surgery evaluation. These patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may still undergo imaging studies to locate the area of vascular obstruction or stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) as part of surgical planning.

Non-invasive techniques

These studies are used to establish the diagnosis:

• Ankle-brachial index Ankle-brachial index Comparison of the blood pressure between the brachial artery and the posterior tibial artery. It is a predictor of peripheral arterial disease. Cardiovascular Examination
  • Usually the first choice in testing to establish a diagnosis
  • Equals the leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy systolic blood pressure divided by the arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy systolic blood pressure:
    • An ABI < 0.9 indicates PAD (see table below for the severity classification based on ABI).
    • An ABI > 1.3 may indicate noncompressible vessels due to calcification (common in diabetics).
    • If the ABI is > 1.3 and suspicion for PAD is high, consider measuring a BP in the 1st toe or proceed to Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) ultrasound.
• Treadmill exercise test 
  • Indicated for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a classic history suggesting PAD and normal resting ABI (0.91–1.30)
  • ABIs are measured before and after exercise:
    • Normal physiology: ABI should ↑ or stay the same.
    • In PAD: post-exercise ABI ↓ by ≥ 20%

Imaging

These studies are used to evaluate the location and severity of disease:

• Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) ultrasound
  • Noninvasive, but operator-dependent
  • Can determine blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure through arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
  • Measured velocities through diseased portions allow estimation of percent stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS).
• Computed tomography with angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery ( CTA CTA A non-invasive method that uses a ct scanner for capturing images of blood vessels and tissues. A contrast material is injected, which helps produce detailed images that aid in diagnosing vascular diseases. Pulmonary Function Tests)
  • Quick, but requires contrast administration
  • Becoming more commonly utilized to locate stenotic lesions
• Magnetic resonance imaging with angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery ( MRA MRA Imaging of the Heart and Great Vessels)
  • Can avoid ionizing radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
  • High diagnostic accuracy
• Digital subtraction arteriography
  • Reference standard
  • Intravenous contrast is injected imaged with a series of radiographs.
  • Has the highest diagnostic accuracy

Laboratory testing

These studies are not used for the diagnosis of PAD, but can help evaluate risk factors or organ injury:

• Lipid profile Lipid profile Lipid Disorders → hyperlipidemia
• Hemoglobin A1c Hemoglobin A1c Products of non-enzymatic reactions between glucose and hemoglobin a, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin a1c is hemoglobin a with glucose covalently bound to the terminal valine of the beta chain. Glycated hemoglobin a is used as an index of the average blood sugar level over a lifetime of erythrocytes. Diabetes Mellitus → diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
• Homocysteine → hyperhomocysteinemia
• Creatinine → renal disease

Screening Screening Preoperative Care asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship

• Screening Screening Preoperative Care is performed in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who may be asymptomatic but have risk factors or evidence of PAD.
• Important in preventing progression and complications
• Can be used to identify patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at risk for other types of cardiovascular disease
• Again, ABI is the test of choice for establishing the diagnosis.

Management

Lifestyle modification

Lifestyle modification is the 1st line of therapy:

• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
• Diet 
• Exercise therapy program: 
  • Increases blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure
  • Improves endurance and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways tolerance Tolerance Pharmacokinetics and Pharmacodynamics
  • Helps develop collateral circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment
  • Reduces blood cell aggregation Aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Coagulation Studies and blood viscosity Blood viscosity The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. Vascular Resistance, Flow, and Mean Arterial Pressure
• Glycemic control

Medications

• Antiplatelet therapy ( aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), clopidogrel Clopidogrel A ticlopidine analog and platelet purinergic p2y receptor antagonist that inhibits adenosine diphosphate-mediated platelet aggregation. It is used to prevent thromboembolism in patients with arterial occlusive diseases; myocardial infarction; stroke; or atrial fibrillation. Antiplatelet Drugs)
• Risk factor modification:
  • Statin therapy
  • Antihypertensive treatment
  • Vitamins ( folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 and vitamin B₁₂) for hyperhomocysteinemia
• Phosphodiesterase inhibitors Phosphodiesterase inhibitors Phosphodiesterase (PDE) inhibitors are a group of drugs that act by inhibiting PDE enzymes. Phosphodiesterase inhibitors have various mechanisms of action depending on the subtype of PDE targeted, but their main action is increasing the amount of intracellular cAMP or cGMP, which in turn results in physiologic effects such as reducing inflammation, promoting smooth muscle relaxation, and vasodilation. Phosphodiesterase Inhibitors ( cilostazol Cilostazol A quinoline and tetrazole derivative that acts as a phosphodiesterase type 3 inhibitor, with anti-platelet and vasodilating activity. It is used in the treatment of peripheral vascular diseases; ischemic heart disease; and in the prevention of stroke. Phosphodiesterase Inhibitors):
  • Most effective pharmaceutical treatment for improving claudication symptoms
  • Indicated after failure of conservative measures
  • Reduces platelet aggregation Platelet aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Hemostasis and allows arterial vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
• Thrombolysis:
  • Used in arterial thrombosis Arterial Thrombosis Hypercoagulable States or embolism where tissue salvage is thought to be likely
  • Not for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with intermittent claudication Intermittent claudication A symptom complex characterized by pain and weakness in skeletal muscle group associated with exercise, such as leg pain and weakness brought on by walking. Such muscle limpness disappears after a brief rest and is often relates to arterial stenosis; muscle ischemia; and accumulation of lactate. Thromboangiitis Obliterans (Buerger’s Disease) or where tissue is immediately threatened or irreversibly damaged
  • May be catheter-directed

Revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease) therapy

• Goal is to salvage the limb tissue and prevent amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation.
• Indications:
  • Critical limb ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage
  • Failure to improve with lifestyle modification and medications
  • Significant disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment due to symptoms
• Percutaneous transluminal angioplasty Angioplasty Reconstruction or repair of a blood vessel, which includes the widening of a pathological narrowing of an artery or vein by the removal of atheromatous plaque material and/or the endothelial lining as well, or by dilatation (balloon angioplasty) to compress an atheroma. Except for endarterectomy, usually these procedures are performed via catheterization as minimally invasive endovascular procedures. Cardiac Surgery ( PTA PTA A peritonsillar abscess (PTA), also called quinsy, is a collection of pus between the capsule of the palatine tonsil and the pharyngeal muscles. A pta is usually a complication of acute tonsillitis, an infection caused by group a streptococci. Patients often present with a sore throat, trismus, and a muffled voice. Peritonsillar Abscess): 
  • Catheter is inserted into the artery.
  • Balloon is inflated to open an obstruction.
  • Vascular stenting may also be performed.
• Atherectomy:
  • Catheter procedure in which plaque Plaque Primary Skin Lesions is removed from the artery
  • Can be used for in-stent restenosis or in areas where stent placement is not feasible
• Surgical procedures:
  • Endarterectomy Endarterectomy Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. Intestinal Ischemia (direct removal of obstructive plaque Plaque Primary Skin Lesions)
  • Embolectomy (direct removal of a thrombus)
  • Vascular bypass grafting

Complications

Threatened limb Threatened limb Minimal sensory loss, mild-to-moderate muscle weakness, absent arterial doppler tones, requires urgent intervention. Acute Limb Ischemia from acute limb ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage

• Surgical emergency Surgical Emergency Acute Abdomen
• Start a heparin drip.
• Surgical embolectomy should be performed in most circumstances.
• Intraoperative angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery follow-up to ensure normal flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure

Compartment syndrome Compartment Syndrome Compartment syndrome is a surgical emergency usually occurring secondary to trauma. The condition is marked by increased pressure within a compartment that compromises the circulation and function of the tissues within that space. Compartment Syndrome

• Increased risk after prolonged ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage (> 6 hours)
• Occurs due to reperfusion injury Reperfusion injury Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (reperfusion), including swelling; hemorrhage; necrosis; and damage from free radicals. The most common instance is myocardial reperfusion injury. Ischemic Cell Damage → leads to swelling Swelling Inflammation and increased pressure (may result in further ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, and limb loss)
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will develop severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome, and muscle weakness. 
• Limb may feel tense.
• Diagnosis is made by measuring compartment pressures.
• Requires 4-compartment fasciotomy Fasciotomy Surgical incision on the fascia. It is used to decompress compartment pressure (e.g. in compartment syndromes; circumferential burns and extremity injuries) or to release contractures (e.g. in dupuytren’s contracture). Compartment Syndrome

Subclavian steal Subclavian steal A clinically significant reduction in blood supply to the brain stem and cerebellum (i.e., vertebrobasilar insufficiency) resulting from reversal of blood flow through the vertebral artery from occlusion or stenosis of the proximal subclavian or brachiocephalic artery. Common symptoms include vertigo, syncope, and intermittent claudication of the involved upper extremity. Subclavian steal may also occur in asymptomatic individuals. Subclavian Steal Syndrome syndrome

• Retrograde vertebral artery Vertebral artery The first branch of the subclavian artery with distribution to muscles of the neck; vertebrae; spinal cord; cerebellum; and interior of the cerebrum. Lateral Medullary Syndrome (Wallenberg Syndrome) flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure due to subclavian artery stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) or occlusion
• Usually asymptomatic, but upper extremity ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and neurologic symptoms (from vetebrobasilar ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage) indicate severe disease.
• Management is similar to general PAD treatment.

Gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction or limb loss

Amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation is performed when:

• Revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease) has failed or is not possible
• There is progressive gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction
• Uncontrolled infection
• Unrelenting pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways

Differential Diagnosis

• Arterial aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms: abnormal dilation of the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology due to weakening of the arterial wall. Thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus of a popliteal artery Popliteal Artery The continuation of the femoral artery coursing through the popliteal fossa; it divides into the anterior and posterior tibial arteries. Popliteal Fossa: Anatomy aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms can result in symptoms of lower extremity ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will have a cold, pale leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy with absent distal pulses and paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome. Physical exam may reveal a large, pulsatile popliteal artery Popliteal Artery The continuation of the femoral artery coursing through the popliteal fossa; it divides into the anterior and posterior tibial arteries. Popliteal Fossa: Anatomy. Imaging will confirm the diagnosis and differentiate this diagnosis from PAD. Treatment involves surgical repair of the artery.
• Arterial dissection Arterial dissection Arterial dissection is a violation of the structural integrity of the arterial wall that results in blood accumulating between the layers. Dissection of the Carotid and Vertebral Arteries: disruption in the medial layer of the arterial wall, resulting in bleeding into the vessel wall (creating a “ false lumen False lumen Aortic Dissection”), which may be due to connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disorders or from vascular interventions. Occlusion of the “true” lumen may result, causing symptoms of ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage (such as limb-threatening ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage). Ultrasound or CTA CTA A non-invasive method that uses a ct scanner for capturing images of blood vessels and tissues. A contrast material is injected, which helps produce detailed images that aid in diagnosing vascular diseases. Pulmonary Function Tests may be used to establish the diagnosis and will differentiate this condition from PAD. Treatment may require surgical repair of the artery.
• Thromboembolic disease: vascular occlusion due to a dislodged thrombus from a more proximal source. The presentation depends on the source, size, and location of the embolism, but includes acute limb ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and blue toe syndrome. The clinical history, hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States workup, and imaging aid in the diagnosis, and a source will typically be suspected or found on workup, which differentiates thromboembolic disease from PAD. Management includes anticoagulation Anticoagulation Pulmonary Hypertension Drugs and revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease).
• Popliteal artery Popliteal Artery The continuation of the femoral artery coursing through the popliteal fossa; it divides into the anterior and posterior tibial arteries. Popliteal Fossa: Anatomy entrapment syndrome: an uncommon condition in which an abnormally positioned, or enlarged, calf muscle compresses the popliteal artery Popliteal Artery The continuation of the femoral artery coursing through the popliteal fossa; it divides into the anterior and posterior tibial arteries. Popliteal Fossa: Anatomy. The compression Compression Blunt Chest Trauma leads to obstruction of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure to the lower extremity, causing distal extremity ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers, or necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage. The diagnosis is made with imaging, which will differentiate this condition from PAD. Management includes avoiding any inciting exercise and vascular surgery Vascular surgery Vascular surgery is the specialized field of medicine that focuses on the surgical management of the pathologies of the peripheral circulation. The main goal of most vascular procedures is to restore circulatory function to the affected vessels by relieving occlusions or by redirecting blood flow (e.g., bypass). Vascular Surgery evaluation.
• Spinal stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS): compression Compression Blunt Chest Trauma of nerve roots due to narrowing of the spinal canal Spinal Canal The cavity within the spinal column through which the spinal cord passes. Spinal Cord Injuries. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have positional back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and exertional lower extremity pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. The pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways will not be relieved with rest. Other symptoms include weakness, paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome, and diminished reflexes. Unlike PAD, pulses will be intact. The diagnosis is made based on clinical exam and MRI imaging of the spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy. Treatment includes physical therapy Physical Therapy Becker Muscular Dystrophy, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways management, and surgery for severe cases.
• Thromboangiitis obliterans Thromboangiitis Obliterans A non-atherosclerotic, inflammatory thrombotic disease that commonly involves small and medium-sized arteries or veins in the extremities. It is characterized by occlusive thrombosis and fibrosis in the vascular wall leading to digital and limb ischemia and ulcerations. Thromboangiitis obliterans is highly associated with tobacco smoking. Thromboangiitis Obliterans (Buerger’s Disease) (Buerger’s disease): nonatherosclerotic segmental inflammatory disease that affects small to medium-sized vessels of the extremities. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are typically young smokers presenting with distal extremity ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, ulcers, or gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction. Diagnosis is based on clinical findings, vascular testing, and angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery. Other potential diagnoses must be ruled out, including PAD. Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation is an essential part of management and decreases the risk of amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation.
• Vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus: a vascular inflammatory disease, often resulting in ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, and organ damage. Any vessel can be involved. Etiologies include autoimmune disorders, drugs, and infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, arthralgias, and arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, as well as potential end-organ damage. Diagnosis involves inflammatory markers, autoimmune serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, infectious workup, and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, which will differentiate this disease from PAD. Management depends on the underlying cause.