Edema (oedema)
It is a clinically evident
increase in the volume of fluid (usually interstitial fluid, but in some cases, intracellular fluid may also increase) in a part of the body. This is a general
definition of edema, while there are many types of edema, e.g. peripheral
edema, unilateral edema of an extremity or a part of an extremity, generalized
edema (anasarca), pulmonary edema, and cerebral edema. These different types of
edema have different clinical manifestations, depending on the body part or the
organ affected and on the underlying cause.The history should include the time of onset (acute edema if it is present <72 hours), any other symptoms (e.g. pain, dyspnea, etc), systemic disease and important risk factors for systemic disease (e.g. history of heart failure, renal disease or hepatic disease, hypertension, diabetes, alcoholism, thyroid disease), medications, risk factors for deep venous thrombosis (e.g. recent surgery, trauma, prolonged immobilization, cancer), any history of allergy. The physical examination should assess for any signs of systemic disease (e.g. signs of heart disease, hepatic disease, or thyroid disease), as well as for the characteristic features of the edema such as its location and severity, if it is unilateral or bilateral, if it is pitting or non-pitting, skin temperature, skin color, etc.
Pitting is characteristically present in some, but not all, types of edema. Pitting refers to an indentation that remains in the edematous area after pressure is applied. Pitting occurs when the edematous fluid in the interstitial space has a low concentration of protein. This is the case in edema associated with decreased plasma oncotic pressure (e.g. in nephrotic syndrome, cirrhosis) or with increased capillary hydrostatic pressure (e.g. in congestive heart failure, deep venous thrombosis). Non-pitting edema is observed in lymphedema (except from the early phase which may manifest pitting edema), allergic edema or angioedema, and myxedema.
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| Pitting edema in a patient with congestive heart failure |
Pathophysiology and etiology of edema
Water constitutes over 50% of the body weight, usually on average about 50-65 % of the body weight. (This percentage is less when there is an increase in body fat, because fat tissue contains less water). The intracellular fluid contains approximately two-thirds of total body water, while the remaining one-third constitutes the extracellular fluid. The plasma (intravascular fluid) contains ¼ of the extracellular fluid.
The remainder ¾ of the extracellular fluid comprise the interstitial fluid. This is the fluid that surrounds cells providing them with oxygen and nutrients and receiving their waste products. Edema represents an excess of interstitial fluid that has become clinically evident.
Edema occurs as a result of:
►Increased movement of water from the intravascular to the interstitial space or
●Increased capillary hydrostatic pressure
In left sided heart failure the pulmonary venous pressure increases and this leads to an elevated pulmonary capillary pressure. This in severe cases leads to pulmonary edema.
●Decreased plasma oncotic pressure
●Increased capillary permeability
●Obstruction of the lymphatic system
● Increased oncotic pressure in the interstitial space
This occurs when there is increased capillary permeability leading to leakage of protein in the extravascular space.
Etiology of edema
Edema can be unilateral or bilateral. The most common cause of unilateral or bilateral leg edema is chronic venous insufficiency.
Unilateral edema of the leg is the result of local mechanical or inflammatory processes. These include:
Thrombophlebitis-Deep venous thrombosis (DVT)
In thrombophlebitis, there is usually sudden onset of unilateral edema with pain, tenderness, and redness of the affected extremity, which is also warmer than the contralateral extremity. Occasionally in thrombophlebitis pain may be absent. Thus, the absence of pain does not eliminate this diagnosis. Generally in deep venous thrombosis (DVT), edema develops over hours to a few days and it is often accompanied by an increased temperature of the leg and enlarged superficial veins. However, in some cases, symptoms may be minimal and clinical findings are not typical. A history of a predisposing condition is common, such as recent immobilization, recent surgery, extremity injury, and cancer. DVT can be complicated by pulmonary embolism (a serious and often life-threatening complication, usually presenting with dyspnea of sudden onset).
In thrombophlebitis, there is usually sudden onset of unilateral edema with pain, tenderness, and redness of the affected extremity, which is also warmer than the contralateral extremity. Occasionally in thrombophlebitis pain may be absent. Thus, the absence of pain does not eliminate this diagnosis. Generally in deep venous thrombosis (DVT), edema develops over hours to a few days and it is often accompanied by an increased temperature of the leg and enlarged superficial veins. However, in some cases, symptoms may be minimal and clinical findings are not typical. A history of a predisposing condition is common, such as recent immobilization, recent surgery, extremity injury, and cancer. DVT can be complicated by pulmonary embolism (a serious and often life-threatening complication, usually presenting with dyspnea of sudden onset).
Treatment involves therapeutic
doses of anticoagulants (usually LMWH or a DOAC) for 3-6 months.
Lymphedema
Lymphedema results from obstruction of lymphatic drainage leading to an abnormal collection of protein-rich fluid in the interstitium, with subsequent retention of water and swelling of the soft tissue. This protein-rich interstitial fluid stimulates the proliferation of fibroblasts, organization of the fluid, and the development of non-pitting edema. Lymphedema may involve the whole extremity, but it characteristically involves the distal part of the foot, where it begins and the dorsum of the foot, which has the appearance of a hump. The edema is non-pitting (but pitting edema can be present at an early stage of lymphedema). Another feature of lymphedema is the Kaposi-Stemmer sign: the inability to pinch with your fingers a fold of skin on the dorsum of the foot at the base of the second toe. Chronic lymphedema is also characterized by thickening of the overlying skin, which may develop a “cobblestone” appearance. Treatment of lymphedema includes elevating the affected limb, complex physical therapy (this is a first-line treatment) and compression stockings, weight loss if the patient is overweight, avoidance of constrictive clothing, and maintenance of appropriate hygiene and skin care.
Cellulitis is an infection of the deep dermis and subcutaneous tissues. The most common causative organisms are Streptococcus and Staphylococcus aureus. Erysipelas is a type of cellulitis caused by group A beta-hemolytic streptococci. In cellulitis there is redness, pain and locally increased temperature of the extremity. Erythema, tenderness of the skin, and skin warmth is usually localized to a well-demarcated area of the extremity. In some cases an obvious source of entry of infection, e.g. leg ulcer or insect bite, maybe present. Lymphangitic spread (red lines streaking away from the area of infection) can be present. Depending on the severity of the infection the patient may be febrile and systemically unwell. Treatment is with antibiotics. Mild cases are usually treated with PO antibiotics such as dicloxacillin, amoxicillin-clavulanate, or cephalexin. If the patient is allergic to penicillin clindamycin or a macrolide (clarithromycin or azithromycin) can be used instead. Severe cases are treated with parenteral antibiotics.
A ruptured gastrocnemius muscle
A ruptured gastrocnemius muscle is a condition that may occur in athletes (runners). It causes calf edema and midcalf pain of sudden onset. An ecchymosis at the ankle is often present.
Lymphedema
Lymphedema results from obstruction of lymphatic drainage leading to an abnormal collection of protein-rich fluid in the interstitium, with subsequent retention of water and swelling of the soft tissue. This protein-rich interstitial fluid stimulates the proliferation of fibroblasts, organization of the fluid, and the development of non-pitting edema. Lymphedema may involve the whole extremity, but it characteristically involves the distal part of the foot, where it begins and the dorsum of the foot, which has the appearance of a hump. The edema is non-pitting (but pitting edema can be present at an early stage of lymphedema). Another feature of lymphedema is the Kaposi-Stemmer sign: the inability to pinch with your fingers a fold of skin on the dorsum of the foot at the base of the second toe. Chronic lymphedema is also characterized by thickening of the overlying skin, which may develop a “cobblestone” appearance. Treatment of lymphedema includes elevating the affected limb, complex physical therapy (this is a first-line treatment) and compression stockings, weight loss if the patient is overweight, avoidance of constrictive clothing, and maintenance of appropriate hygiene and skin care.
Cellulitis is an infection of the deep dermis and subcutaneous tissues. The most common causative organisms are Streptococcus and Staphylococcus aureus. Erysipelas is a type of cellulitis caused by group A beta-hemolytic streptococci. In cellulitis there is redness, pain and locally increased temperature of the extremity. Erythema, tenderness of the skin, and skin warmth is usually localized to a well-demarcated area of the extremity. In some cases an obvious source of entry of infection, e.g. leg ulcer or insect bite, maybe present. Lymphangitic spread (red lines streaking away from the area of infection) can be present. Depending on the severity of the infection the patient may be febrile and systemically unwell. Treatment is with antibiotics. Mild cases are usually treated with PO antibiotics such as dicloxacillin, amoxicillin-clavulanate, or cephalexin. If the patient is allergic to penicillin clindamycin or a macrolide (clarithromycin or azithromycin) can be used instead. Severe cases are treated with parenteral antibiotics.
A ruptured gastrocnemius muscle
A ruptured gastrocnemius muscle is a condition that may occur in athletes (runners). It causes calf edema and midcalf pain of sudden onset. An ecchymosis at the ankle is often present.
A ruptured Baker’s cyst
A Baker's cyst is an enlarged bursa resulting from an accumulation of synovial fluid in the popliteal fossa. Most Baker cysts are small and asymptomatic. When they become large (> 5 cm), the patient will notice a swelling behind the knee and also a decreased range of motion. Baker cysts are usually caused by arthritis, injury, or overuse of the knee, conditions that may result in the increased production of synovial fluid. When a baker cyst ruptures, it manifests with calf swelling, redness, and warmth, (simulating deep vein thrombosis).
An acquired or inherited
arteriovenous fistula (rare).
Bilateral leg edema or generalized edema is often due to systemic conditions, including
It can cause bilateral non-tender pitting edema in dependent areas of the body. Other clinical features often present in heart failure include dyspnea (on exertion or paroxysmal nocturnal dyspnea with orthopnea), fatigue, and physical examination findings of elevated jugular venous pressure, gallop rhythm on heart auscultation or basilar crackles on lung auscultation, Tests that can aid in the diagnosis are echocardiography and an elevated BNP.
Pulmonary hypertension
Leg edema may appear at an early stage of pulmonary hypertension. Physical examination may reveal a loud pulmonic component of the second heart sound (loud P2) and signs of elevated jugular venous pressure.
Kidney disease such as nephrotic syndrome, acute glomerulonephritis, renal failure
Kidney disease causes soft pitting edema, which is generalized and often involves not only dependent areas of the body but also the face and especially the eyelids. The nephrotic syndrome is characterized by marked proteinuria ( > 3.5 g/day), low plasma albumin, and elevated plasma cholesterol. Renal disease can also cause edema without hypoproteinemia, due to an increased plasma volume (salt and water retention). In renal failure blood urea nitrogen ( BUN) and creatinine are elevated. Urinalysis is a useful test since it may reveal signs of kidney disease, such as protein and blood in the urine (microscopic hematuria).
Hepatic cirrhosis
There is usually a history of alcoholism or hepatitis. Malaise and anorexia are common in a liver disorder or in renal failure, however they are nonspecific symptoms ( also common in advanced cancer, advanced heart failure, a systemic infection, etc.) Findings suggestive of hepatic disease include palmar erythema, easy bruising, jaundice, spider angiomata, hepatomegaly, and ascites.
Bilateral leg edema or generalized edema is often due to systemic conditions, including
It can cause bilateral non-tender pitting edema in dependent areas of the body. Other clinical features often present in heart failure include dyspnea (on exertion or paroxysmal nocturnal dyspnea with orthopnea), fatigue, and physical examination findings of elevated jugular venous pressure, gallop rhythm on heart auscultation or basilar crackles on lung auscultation, Tests that can aid in the diagnosis are echocardiography and an elevated BNP.
Pulmonary hypertension
Leg edema may appear at an early stage of pulmonary hypertension. Physical examination may reveal a loud pulmonic component of the second heart sound (loud P2) and signs of elevated jugular venous pressure.
Kidney disease such as nephrotic syndrome, acute glomerulonephritis, renal failure
Kidney disease causes soft pitting edema, which is generalized and often involves not only dependent areas of the body but also the face and especially the eyelids. The nephrotic syndrome is characterized by marked proteinuria ( > 3.5 g/day), low plasma albumin, and elevated plasma cholesterol. Renal disease can also cause edema without hypoproteinemia, due to an increased plasma volume (salt and water retention). In renal failure blood urea nitrogen ( BUN) and creatinine are elevated. Urinalysis is a useful test since it may reveal signs of kidney disease, such as protein and blood in the urine (microscopic hematuria).
Hepatic cirrhosis
There is usually a history of alcoholism or hepatitis. Malaise and anorexia are common in a liver disorder or in renal failure, however they are nonspecific symptoms ( also common in advanced cancer, advanced heart failure, a systemic infection, etc.) Findings suggestive of hepatic disease include palmar erythema, easy bruising, jaundice, spider angiomata, hepatomegaly, and ascites.
Hypoalbuminemia
This may result from nephrotic syndrome cirrhosis, malnutrition, and protein-losing enteropathy. In contrast to cardiac edema, hypoproteinemic edema is less dependent on body position. The face, and particularly the eyelids are often affected, although edema is often present in the lower extremities too. Like cardiac edema, also this form of edema is soft and pitting. The diagnosis of hypoalbuminemia is made by finding low levels of plasma albumin (normal levels 3.5-5.4 g/dl). Hypoproteinemic edema occurs if the plasma albumin content is below 2.5 g/dL or total plasma protein level is less than 5 g/dL.
Very low levels of albumin, below 2 g/dL (20g/L) are also accompanied by a predisposition to thrombosis because the plasma
level of antithrombin III also decreases.
Drugs
Drugs can cause edema either by vasodilation or by salt and fluid retention. Drugs that may cause edema are some antihypertensives (calcium channel blockers, hydralazine, minoxidil, methyldopa), NSAIDS (non-steroidal anti-inflammatory drugs), hormones (estrogens, progesterone, oral contraceptives, corticosteroids, androgens), pioglitazone (hypoglycemic drug), trazodone (antidepressant), neurotrophic agents (gabapentin, pregabalin, these may cause edema of hands and feet), chemotherapeutics (cyclosporine, cyclophosphamide, mitramycin)
Allergic reaction or angioedema
These conditions cause acute edema due to increased capillary permeability. Edema often affects the face. If it involves the larynx, it can cause a form of upper airway obstruction with stridor and dyspnea (a dangerous condition requiring immediate treatment, also see the chapter on upper respiratory obstruction).
Sleep apnea
It has been associated with pedal edema because it causes pulmonary hypertension and hence increased venous pressure and capillary hydrostatic pressure
Exposure to extremes of temperature
Bilateral leg edema may also result from local causes, such as:
Chronic venous insufficiency
Its clinical features have been described above. Edema caused by venous insufficiency improves with recumbence (i.e. edema is less early in the morning after sleep) and with elevation of the legs and worsens with dependency (it is often worse at the end of the day, after sitting or standing).
Constricting garments,
Prolonged dependency of the legs.
Primary lymphedema
It may present in neonates, adolescents, or young adults and is the result of a genetic malfunction of the lymphatic system.
This may result from nephrotic syndrome cirrhosis, malnutrition, and protein-losing enteropathy. In contrast to cardiac edema, hypoproteinemic edema is less dependent on body position. The face, and particularly the eyelids are often affected, although edema is often present in the lower extremities too. Like cardiac edema, also this form of edema is soft and pitting. The diagnosis of hypoalbuminemia is made by finding low levels of plasma albumin (normal levels 3.5-5.4 g/dl). Hypoproteinemic edema occurs if the plasma albumin content is below 2.5 g/dL or total plasma protein level is less than 5 g/dL.
Very low levels of albumin, below 2 g/dL (20g/L) are also accompanied by a predisposition to thrombosis because the plasma
level of antithrombin III also decreases.
Drugs
Drugs can cause edema either by vasodilation or by salt and fluid retention. Drugs that may cause edema are some antihypertensives (calcium channel blockers, hydralazine, minoxidil, methyldopa), NSAIDS (non-steroidal anti-inflammatory drugs), hormones (estrogens, progesterone, oral contraceptives, corticosteroids, androgens), pioglitazone (hypoglycemic drug), trazodone (antidepressant), neurotrophic agents (gabapentin, pregabalin, these may cause edema of hands and feet), chemotherapeutics (cyclosporine, cyclophosphamide, mitramycin)
Allergic reaction or angioedema
These conditions cause acute edema due to increased capillary permeability. Edema often affects the face. If it involves the larynx, it can cause a form of upper airway obstruction with stridor and dyspnea (a dangerous condition requiring immediate treatment, also see the chapter on upper respiratory obstruction).
Sleep apnea
It has been associated with pedal edema because it causes pulmonary hypertension and hence increased venous pressure and capillary hydrostatic pressure
Exposure to extremes of temperature
Bilateral leg edema may also result from local causes, such as:
Chronic venous insufficiency
Its clinical features have been described above. Edema caused by venous insufficiency improves with recumbence (i.e. edema is less early in the morning after sleep) and with elevation of the legs and worsens with dependency (it is often worse at the end of the day, after sitting or standing).
Constricting garments,
Prolonged dependency of the legs.
Primary lymphedema
It may present in neonates, adolescents, or young adults and is the result of a genetic malfunction of the lymphatic system.
Idiopathic edema,
Lipedema
Lipedema, although it appears as a form of swelling (increased circumference) of the lower extremities is not true edema. It is more accurately considered a form of fat maldistribution. In lipedema, the edema is symmetric, observed in the hips and both legs due to abnormal fat distribution, but not in the ankles and feet. A useful feature for the differential diagnosis between lipedema and lymphedema is that the dorsum of the foot is not affected in lipedema but is prominently involved in lymphedema.
Lipedema
Lipedema, although it appears as a form of swelling (increased circumference) of the lower extremities is not true edema. It is more accurately considered a form of fat maldistribution. In lipedema, the edema is symmetric, observed in the hips and both legs due to abnormal fat distribution, but not in the ankles and feet. A useful feature for the differential diagnosis between lipedema and lymphedema is that the dorsum of the foot is not affected in lipedema but is prominently involved in lymphedema.
Treatment of edema
Treatment depends on the cause. In case of edema due to fluid overload resulting from a cardiac, renal, or hepatic disease, treatment includes dietary sodium restriction, loop diuretics (furosemide, or torasemide), and in some cases also aldosterone antagonists (mineralocorticoid receptor antagonists, such as spironolactone or eplerenone). Renal function and serum electrolytes should be periodically assessed because both the treatment and the underlying disease may induce significant changes in these laboratory values. Further treatment is dictated by the causative disease.GO BACK TO THE TABLE OF CONTENTS:
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