Chronic Venous Insufficiency (Clinical)

Overview

Definition

Chronic venous disease Chronic venous disease Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease (like varicose veins) and include skin pigmentation, stasis dermatitis, lipodermatosclerosis, and eventually, the development of ulcers. Chronic Venous Insufficiency is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous 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.

Epidemiology^[2,7,10]

• Females > males
• Lifetime incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of chronic venous disease Chronic venous disease Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease (like varicose veins) and include skin pigmentation, stasis dermatitis, lipodermatosclerosis, and eventually, the development of ulcers. Chronic Venous Insufficiency: up to 50% of individuals
• Lifetime incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of chronic venous insufficiency Chronic venous insufficiency Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. “Chronic venous insufficiency” refers to the more severe forms of chronic venous disease. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease. Chronic Venous Insufficiency:
  • Up to 40% of women 
  • Up to 17% of men 
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency ↑ with age

Etiology^[1,2,10]

• Chronic venous hypertension Chronic venous hypertension Chronic Venous Insufficiency
• Causes of venous 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:
  • Obstruction: usually deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus ( DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis)
  • Reflux (retrograde venous 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):
    • Usually due to valve incompetence
    • Valve incompetence may develop after obstruction.
• Primary disease: symptomatic presentation without a precipitating event (70%)
• Secondary disease: develops after obstruction due to DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis (30%)
• Risk factors for chronic venous insufficiency Chronic venous insufficiency Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. “Chronic venous insufficiency” refers to the more severe forms of chronic venous disease. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease. Chronic Venous Insufficiency:
  • ↑ Age
  • ↑ BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity
  • Family history Family History Adult Health Maintenance of venous disease
  • Laxity of ligaments (hernias, flat feet)
  • Prolonged standing
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Prior DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis
  • Klippel–Trenaunay syndrome Klippel–Trenaunay syndrome A congenital disorder that is characterized by a triad of capillary malformations (hemangioma), venous malformations (arteriovenous fistula), and soft tissue or bony hypertrophy of the limb. This syndrome is caused by mutations in the vg5q gene which encodes a strong angiogenesis stimulator. Chronic Venous Insufficiency (includes congenital Congenital Chorioretinitis absence of venous valves)
  • ↑ Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy states, including pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

Pathophysiology

Venous 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^[1,2,7]

• DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis (obstruction) and/or primary valve incompetence (reflux) can cause:
  • ↑ Venous pressure in deep veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology 
  • ↑ Pressure in perforating veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology 
  • ↑ Pressure in superficial veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology 
• Endothelial dysfunction of vein walls ensues from DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis.
• Chronic inflammation Chronic Inflammation Inflammation of vein walls leads to eventual remodeling of those vein walls:
  • ↑ Type 1 Type 1 Spinal Muscular Atrophy collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology
  • ↓ Type 3 Type 3 Spinal Muscular Atrophy collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology
  • ↓ Smooth muscle cells 
  • Degradation of the 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
  • ↑ Proteinases lead to increased permeability.
• Severe wall dysfunction increases the risk of DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis due to:
  • Inability to properly move blood forward (stagnation)
  • Chronic inflammation Chronic Inflammation Inflammation/endothelial damage

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 and soft tissue Soft Tissue Soft Tissue Abscess changes^[1,2,7]

• The increase in venous 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 is combined with increased vessel permeability.
• This leads to efflux of blood components into the subcutaneous space:
  • Fluid → edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema → ↑ pressure in the extremity, which may lead to:
    • Necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
    • Impaired lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs drainage → further fluid accumulation and impaired waste removal
  • RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology (which break down) → hemosiderin Hemosiderin Heme Metabolism deposits → 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 pigmentation
  • Proteinases → cutaneous ulcers
  • WBCs → cytokine release → subcutaneous fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans ( lipodermatosclerosis Lipodermatosclerosis Chronic Venous Insufficiency) → ↓ capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology in these areas:
    • White plaques ( atrophie blanche Atrophie blanche Chronic Venous Insufficiency) 
    • ↓ 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 → poor healing and 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

Clinical Presentation

Spectrum of chronic venous disease Chronic venous disease Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease (like varicose veins) and include skin pigmentation, stasis dermatitis, lipodermatosclerosis, and eventually, the development of ulcers. Chronic Venous Insufficiency^[1-3]

• Asymptomatic venous dilation
• Mild disease:
  • Telangiectasias Telangiectasias Ataxia-telangiectasia
  • Reticular veins Reticular veins Chronic Venous Insufficiency
  • Varicose veins Varicose veins Enlarged and tortuous veins. Chronic Venous Insufficiency
  • Mild dependent ankle edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
• Severe disease ( chronic venous insufficiency Chronic venous insufficiency Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. “Chronic venous insufficiency” refers to the more severe forms of chronic venous disease. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease. Chronic Venous Insufficiency):
  • Significant edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • 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 changes 
  • Ulcers

Presenting symptoms^[10]

• Dependent pitting edema Pitting edema Edema caused by excess fluid without excess colloid. Leaves “pits” due to fluid displacement when pressure is applied to the area Edema 
• Lower extremity pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or discomfort:
  • Often described as “heavy legs,” throbbing, aching, or cramping
  • Worse with standing
  • In contrast to peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease (PAD), pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways improves with:
    • 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 elevation
    • Walking
• Numbness or tingling Tingling Posterior Cord Syndrome
• Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
• Visible tortuous veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology:
  • Telangiectasias Telangiectasias Ataxia-telangiectasia: dilated intradermal venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology < 1 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
  • Reticular veins Reticular veins Chronic Venous Insufficiency: dilated subdermal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology, 1–3 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 in diameter 
  • Varicose veins Varicose veins Enlarged and tortuous veins. Chronic Venous Insufficiency: dilated subcutaneous veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology > 3 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 in diameter
• 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 changes:
  • Brown or blue-gray discoloration of the skin blue-gray discoloration of the skin Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) from hemosiderin Hemosiderin Heme Metabolism deposits
  • Stasis dermatitis Stasis dermatitis Chronic Venous Insufficiency (eczematous rash Rash Rocky Mountain Spotted Fever) characterized by:
    • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Scaling
    • Weeping
    • Erosions Erosions Corneal Abrasions, Erosion, and Ulcers
    • Crusting
  • Lipodermatosclerosis Lipodermatosclerosis Chronic Venous Insufficiency:
    • Firm, indurated areas
    • 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 is tacked down to the subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess (subcutaneous fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans).
    • Most common at the medial ankle
    • May form a constrictive band around the extremity
  • Atrophie blanche Atrophie blanche Chronic Venous Insufficiency:
    • Atrophic white plaques with red punctate dots or telangiectasias Telangiectasias Ataxia-telangiectasia
    • Circular or stellate
    • Surrounded by hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi
  • Ulcers: commonly over the medial malleolus Medial malleolus Ankle Joint: Anatomy

Diagnosis and Classification

Physical exam^[4,7,8,10]

Lower extremity appearance:

• Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema 
• Visible or palpable tortuous superficial veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
• Characteristic 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 changes
• +/– Ulcers

Venous refilling time Venous refilling time Chronic Venous Insufficiency (photoplethysmography (PPG)):^[15]

• Assesses venous function Venous function Veins transport deoxygenated blood and waste products from capillaries in the periphery back to the heart. Veins are capacitance vessels, meaning that they can stretch significantly, increasing the volume of fluid they can hold without significantly increasing their pressure. Venous Function
• A probe Probe A device placed on the patient’s body to visualize a target Ultrasound (Sonography) containing both an LED light and a photosensor to measure backscatter, is placed over the medial ankle → can determine changes in blood volume in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions
• 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 veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology are emptied using calf contraction.
• Venous refill time: time required for the PPG tracing to return to 90% of baseline after cessation of calf contraction
• Refilling time of < 20 seconds is indicates venous reflux consistent with CVI.^[15]

Ankle–brachial index:

• Done to identify the presence of PAD, which often coexists with CVI in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with venous 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 ulcers^[8]
• Ankle–brachial index = ratio of blood pressure of the ankle to blood pressure of 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 
• Ankle–brachial index ≤ 0.9 → PAD
• Important: Compression Compression Blunt Chest Trauma therapy (standard in venous insufficiency) is contraindicated in PAD.

Other: heart, lung, and abdominal exams:

• Heart and lung exam: Look for evidence of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) (e.g., dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, jugular venous distension Jugular Venous Distension Cardiovascular Examination, S3 S3 Heart Sounds heart sound).
• Abdominal exam: Look for evidence of cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis (e.g., jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, GI bleeding).

Imaging^[5,10,12]

Duplex ultrasonography Duplex ultrasonography Ultrasonography applying the doppler effect combined with real-time imaging. The real-time image is created by rapid movement of the ultrasound beam. A powerful advantage of this technique is the ability to estimate the velocity of flow from the doppler shift frequency. Hypercoagulable States:^[5,8,10,12]

• Indicated when working up CVI^[5,8,10,15]
• 1st-line test to:
  • Confirm the diagnosis (if in question)→ the presence of venous reflux confirms CVI^[5]
  • Determine the etiology
  • Rule out a DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis
  • Assess the severity of deep vein disease
  • Localize affected anatomy
• Combines:
  • B-mode imaging of deep and superficial veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
  • 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) assessment 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
• Examination to rule out DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis:^[12]
  • From the inguinal ligament Inguinal Ligament Femoral Region and Hernias: Anatomy to the ankle (when feasible)
  • Compression Compression Blunt Chest Trauma is applied every 2 cm or less in the transverse plane Transverse plane Anterior Abdominal Wall: Anatomy.
  • Obstruction shows:
    • Absence 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
    • Noncompressible veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
• Examination for venous reflux:^[12,15]
  • Compares baseline spectral Doppler Spectral Doppler Ultrasound (Sonography) waveforms with those following provocative maneuvers (measured along the long axis of the vein)
  • Patient should be standing (or in the reverse Trendelenburg position).
  • Reflux shows:
    • Reversal 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
    • > 0.5 second in the superficial and perforator veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
    • > 1 second in deep veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology

Cross-sectional venography Venography Budd-Chiari Syndrome with CT or MRI:^[5,10]

• Used to evaluate the deep venous system poorly accessible by ultrasound (e.g., infrainguinal area)
• Consider in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with:
  • Normal or equivocal ultrasound
  • Unilateral 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 edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema suggesting iliac vein obstruction → can identify abdominopelvic masses

Catheter-based (invasive) venography Venography Budd-Chiari Syndrome:

• Gold standard test
• Rarely needed to make diagnosis
• Used prior to more invasive intervention

Testing on venous 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 ulcers^[8]

• Serial measurements (baseline measurements; also used to determine the effects of treatments)
• Culture only when there is clinical evidence of infection, which can include:
  • Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis
  • Purulent drainage
  • Discolored, friable granulation Granulation Wound Healing tissue
  • Necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • A visible biofilm Biofilm Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an extracellular polymeric substance matrix that is secreted by the microbes. They occur on body surfaces such as teeth (dental deposits); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with dentifrices; disinfectants; anti-infective agents; and anti-fouling agents. Staphylococcus
  • Ulcer progression
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma indications:
  • Wounds do not respond to 4‒6 weeks of standard therapy.
  • Ulcers with atypical features to rule out malignancy Malignancy Hemothorax (possible, but rare)

Clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification of chronic venous disease Chronic venous disease Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease (like varicose veins) and include skin pigmentation, stasis dermatitis, lipodermatosclerosis, and eventually, the development of ulcers. Chronic Venous Insufficiency^[4,13]

• Clinical signs: 
  • C0: no visible or palpable disease
  • C1: telangiectasias Telangiectasias Ataxia-telangiectasia and reticular veins Reticular veins Chronic Venous Insufficiency
  • C2: varicose veins Varicose veins Enlarged and tortuous veins. Chronic Venous Insufficiency
  • C3: edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • C4: 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 changes
    • C4_a: pigmentation or stasis dermatitis Stasis dermatitis Chronic Venous Insufficiency (eczematous rash Rash Rocky Mountain Spotted Fever)
    • C4_b: lipodermatosclerosis Lipodermatosclerosis Chronic Venous Insufficiency
  • C5: healed ulcer
  • C6: active ulcer
  • C6_R: recurrent active ulcer
• Etiology:
  • Ep EP Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy: primary causes, usually degeneration of valves leading to reflux
  • Es: secondary causes, usually DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis or trauma
    • Esi: intravenous secondary causes (e.g., DVTs)
    • Ese: extraneous secondary causes (e.g., extrinsic compression Compression Blunt Chest Trauma)
  • Ec: congenital Congenital Chorioretinitis causes
  • En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum: no identified cause
• Anatomy (standardized terminology identifying the location of the lesion):
  • As: superficial veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology (within the subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess)
  • Ad AD The term advance directive (AD) refers to treatment preferences and/or the designation of a surrogate decision-maker in the event that a person becomes unable to make medical decisions on their own behalf. Advance directives represent the ethical principle of autonomy and may take the form of a living will, health care proxy, durable power of attorney for health care, and/or a physician’s order for life-sustaining treatment. Advance Directives: deep veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology (within the muscle compartments bound by fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis)
  • Ap: perforating veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology ( veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology that connect superficial to deep veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology by traversing the muscular fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis)
• Pathophysiology:
  • Pr: venous reflux ( retrograde flow Retrograde flow Veins: Histology)
  • Po: venous obstruction ( thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus)
  • Pr,o: both reflux and obstruction
  • Pn: neither reflux nor obstruction
  • Pn: neither reflux nor obstruction
• Example: C2,4_a,Es,As,d,Pr,o

Venous clinical severity score^[10,16]

• A complement for the CEAP classification CEAP classification Chronic Venous Insufficiency system
• Allows for serial assessment during longitudinal follow-up
• Clinical features are evaluated on a scale Scale Dermatologic Examination of 0‒3 (with 3 being “most severe”) for each 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.
• A total score is calculated to determine the overall severity of clinical disease.

Management^[6-11]

Goals

Management may vary based on practice location. The following information is based on US and European guidelines.

• Reduce edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema.
• Reduce discomfort.
• Prevent and treat 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 manifestations.
• Heal ulcers.
• Improve modifiable risk factors.

Conservative (nonsurgical) management

• General:
  • Frequent 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 elevation (30 minutes, 3–4 times daily)  → improve venous drainage
  • Exercise → improve calf muscle pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery → ↓ pressure
• 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 care:
  • Cleansing
  • Emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea:
    • To maintain 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 barrier
    • Prevent dryness and fissuring
    • ↓ Scratching (which can lead to ulcers)
• Compression Compression Blunt Chest Trauma therapy (hosiery):^[14]
  • Primary initial management technique
  • Graded compression Compression Blunt Chest Trauma stockings provide gradually decreasing pressure up the length of the stocking
  • Available in different pressure gradients:
    • < 20 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 → for CEAP C1‒3
    • 20‒30 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 → for CEAP C2‒3
    • 30‒40 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 → for CEAP C4‒6 (commonly used)
    • > 40 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 → typically for recurrent ulcers, chronic lymphedema Lymphedema Edema due to obstruction of lymph vessels or disorders of the lymph nodes. Lymphatic Filariasis (Elephantiasis) or burn scars
  • Should be appropriately fitted to the patient (measurements should be taken in the morning when edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema is lowest)^[10,14]
  • Compression Compression Blunt Chest Trauma bandages (e.g., Profore):^[14]
    • An alternative to stockings
    • Applied by trained personnel 
    • Changed once or twice weekly (depending on amount of drainage)
  • Contraindicated with coexisting PAD
  • Long-term adherence required^[10]
• Venoactive substances to ↑ venous tone:
  • Used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with:
    • Resistant edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema in spite of compression Compression Blunt Chest Trauma therapy
    • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to compression Compression Blunt Chest Trauma therapy
  • Options (dietary supplements in the US, drugs in Europe):^[6,10]
    • Escin Escin Pentacyclic triterpene saponins, biosynthesized from protoaescigenin and barringtogenol, occurring in the seeds of aesculus. It inhibits edema formation and decreases vascular fragility. Chronic Venous Insufficiency (horse chestnut seed extract),
      • Stimulates release of prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids → venoconstriction Venoconstriction Venous Function
      • May help with 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 pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
      • Dose: 300 mg by mouth twice daily 
    • Micronized purified flavonoid fraction Micronized purified flavonoid fraction Chronic Venous Insufficiency (MPFF):
      • May help heal ulcers and reduce edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Dosage Dosage Dosage Calculation depends on the formulation and situation (consider consulting with a specialist for dosing)
• Ineffective therapies with no definite proven value:
  • Hyperbaric oxygen Hyperbaric oxygen The therapeutic intermittent administration of oxygen in a chamber at greater than sea-level atmospheric pressures (three atmospheres). It is considered effective treatment for air and gas embolisms, smoke inhalation, acute carbon monoxide poisoning, caisson disease, clostridial gangrene, etc. The list of treatment modalities includes stroke. Decompression Sickness
  • Electromagnetic therapy
  • Therapeutic ultrasound

Ulcer care^[6]

• Debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome:
  • Removes surrounding necrotic tissue
  • Promotes healthy granulation Granulation Wound Healing tissue
  • Enhances reepithelialization
  • ↓ Risk for infection
  • May be done using surgical, enzymatic, or biologic methods
• Topical agents (most do not improve healing rates):
  • Cadexomer iodine Cadexomer iodine Chronic Venous Insufficiency
  • Silver sulfadiazine Sulfadiazine One of the short-acting sulfonamides used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. Sulfonamides and Trimethoprim
  • Avoid topical antiseptics.
• Systemic antibiotics: only in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with acute cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis or clinically infected ulcer
• Dressings
• Medical options for treating resistant ulcers:
  • Stanozolol Stanozolol A synthetic steroid that has anabolic and androgenic properties. Androgens and Antiandrogens: an anabolic steroid that stimulates fibrinolysis
  • Pentoxifylline Pentoxifylline A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. Phosphodiesterase Inhibitors:
    • ↑ microcirculation and tissue oxygenation
    • Dose: 400 mg orally 3 times daily^[10]
  • MPFFs
  • Individuals not responding to medical management should be referred to a venous specialist.^[6]

Surgical management

Goals:

• Occlude (or remove) the damaged vessels and restore proper 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 
• Decrease venous 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 to reduce edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and 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 effects

Indications:^[9]

• Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or discomfort
• Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
• Varix hemorrhage
• Recurrent superficial phlebitis Phlebitis Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (thrombophlebitis). Glycopeptides
• Stasis dermatitis Stasis dermatitis Chronic Venous Insufficiency
• Ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers
• CEAP classification CEAP classification Chronic Venous Insufficiency of ≥ C2

Options include:^[10]

• Endovenous ablation (thermal destruction)
  • Laser ablation
  • Radiofrequency ablation Radiofrequency ablation Removal of tissue using heat generated from electrodes delivering an alternating electrical current in the frequency of radio waves. Hepatocellular Carcinoma (HCC) and Liver Metastases
• Sclerotherapy Sclerotherapy Treatment of varicose veins, hemorrhoids, gastric and esophageal varices, and peptic ulcer hemorrhage by injection or infusion of chemical agents which cause localized thrombosis and eventual fibrosis and obliteration of the vessels. Hemorrhoids (injection of toxic substances causing fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and occlusion)
• Phlebectomy (vein excision)
• 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 and stenting (relieve obstructions in the deep veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology)
• Typically performed by vascular specialists at referral centers
• Valve repair (deep veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology)
  • Rarely performed
  • Better for primary (rather than post-thrombotic) venous reflux

Complications

• Bleeding from varicose veins Varicose veins Enlarged and tortuous veins. Chronic Venous Insufficiency
• DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis
• Superficial thrombophlebitis Superficial Thrombophlebitis Thromboangiitis Obliterans (Buerger’s Disease):
  • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation within the vein walls → thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
  • Treatment:
    • NSAIDs NSAIDS Primary vs Secondary Headaches
    • Compression Compression Blunt Chest Trauma therapy
• Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis or infected ulcers:
  • Require treatment with systemic antibiotics and debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome
  • May lead to 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

Differential Diagnosis

• Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR): clinical syndrome resulting from dysfunction of the cardiac pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols that leads to low tissue perfusion and congestion in the venous system. Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) can be distinguished from chronic venous insufficiency Chronic venous insufficiency Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. “Chronic venous insufficiency” refers to the more severe forms of chronic venous disease. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease. Chronic Venous Insufficiency by the presence of dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, jugular venous distention, and an S3 S3 Heart Sounds heart sound. Diagnosis is made from a combination of clinical, laboratory, and imaging findings, and management is directed toward medical optimization.
• Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis: progressive fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and failure of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, which leads to portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension. Portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension can cause venous congestion distally, resulting in ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, gastric and esophageal varices, and peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema. Telangiectasias Telangiectasias Ataxia-telangiectasia are also possible. Symptoms also include jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, GI bleeding, neurologic symptoms, and coagulation disorders. Management is mostly supportive, with the goal of reducing complications.
• Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome: Damaged renal podocytes lead to massive proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, which ultimately can result in significant peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema similar to chronic venous disease Chronic venous disease Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease (like varicose veins) and include skin pigmentation, stasis dermatitis, lipodermatosclerosis, and eventually, the development of ulcers. Chronic Venous Insufficiency. It is also associated with a 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 state due to urinary loss of antithrombin Antithrombin Endogenous factors and drugs that directly inhibit the action of thrombin, usually by blocking its enzymatic activity. They are distinguished from indirect thrombin inhibitors, such as heparin, which act by enhancing the inhibitory effects of antithrombins. Anticoagulants III, so DVTs may develop. Renal biopsy Renal Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis will yield a definitive diagnosis. Management is largely supportive and directed at the underlying cause.
• Peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease (PAD): 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 leading to decreased 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 in the peripheral 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, commonly in the lower extremities. The 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 results in claudication ( pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that is induced by exercise and relieved with rest). The decreased arterial 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 in PAD may also lead to ulcers secondary to 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. Diagnosis is established clinically, including an 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) of ≤ 0.9, and supported by vascular imaging. Treatment involves medications and surgical revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease).
• Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) (SCC): a malignant tumor Tumor Inflammation arising from the epidermal keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions, usually in sun-exposed areas. SCCs can form well-demarcated, scaling, pink plaques that can resemble inflammatory 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 changes. Diagnosis is established with a biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. SCC can also arise in chronic venous ulcers. The mainstay of treatment is surgical excision.