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Edema
EDEMA David W. Gibson, MD, and Harry L. Greene II, MD, FACP
Edema is an abnormal collection of fluid in the interstitial space that may be localized or generalized. Fluid movement between the intravascular and extravascular space is related to the interacting forces of hydrostatic pressure, colloid oncotic pressure, and capillary permeability and to the effects of lymphatic drainage. Normally there exists an equilibrium among these forces, and no net fluid accumulation takes place. Edema occurs when there is a decrease in plasma oncotic pressure, an increase in hydrostatic pressure, an increase in capillary permeability, or a combination of these factors. Edema also can be present when lymphatic flow is obstructed. A. The history and physical examination focus on the causes of edema and seek to ascertain whether it is generalized or localized. B. Generalized edema can be documented by weight gain and often is associated with increased capillary hydrostatic pressure as seen in congestive heart failure (CHF), in renal failure with increased sodium and water load, after expansion of the intravascular volume from IV fluids, or in conditions of sodium retention. Edema may occur after corticosteroid therapy or with estrogens or other medications. Edema involving the whole body (e.g., anasarca) may extend to involve the peritoneal cavity (e.g., ascites) or the pleural space (e.g., hydrothorax). In patients with generalized edema the first step is to estimate central venous pressure by determining jugular venous pressure (JVP). The distance from the manubrium sterni to the fluid meniscus in the jugular vein should be 2 cm at 45 degrees or 5 cm from the left atrium. C. Determine serum albumin and urinary protein in patients with generalized edema and normal JVP. D. If serum albumin is normal, perform urinalysis, looking for abnormal urinary sediment, and check BUN and creatinine to evaluate the possibility of renal pathology. If urinalysis findings are normal, order thyroid function tests (TFTs) to look for myxedema. Remaining patients
18
E.
F.
G.
H.
I.
should be considered as possibly having idiopathic edema or drug-induced edema. If serum albumin is decreased, perform urinalysis to check for proteinuria. More than 3.5 g protein suggests nephrotic syndrome; 3.5 g in a normal urinalysis suggests another cause, such as hepatitis or hepatic infiltration disease. Order liver function tests (LFTs); if results are abnormal, evaluate for liver pathology. If LFT results are normal, check prealbumin and cholesterol to evaluate for malnutrition. If the prealbumin is 20 mg/dl and the cholesterol level is low, malnutrition is suggested. If the prealbumin is 20 mg/dl, a capillary leak, abnormal protein synthesis, and proteinlosing enteropathy are all possibilities. In patients with an elevated JVP and generalized edema, order chest radiographs to look for cardiomegaly. If cardiomegaly is found, order an echocardiogram to look for pericardial effusion; pericardial thickening, as in acute or chronic pericarditis; abnormal contractility of the heart, as might be seen in CHF; or signs of infiltrative cardiac problems, such as hypertrophic obstructive cardiomyopathy, amyloid, or neoplasm. If cardiac size is normal on the chest film, evaluate the lung fields for pulmonary hypertension. Such a finding should lead to evaluation for cor pulmonale. Clear lung fields should prompt echocardiography to seek pericardial constriction. Regional edema or localized edema often is caused by increased capillary pressure. Some causes include chronic venous insufficiency; incompetent venous valves; vascular obstructions, either extrinsic because of neoplasm, lymph nodes, surgery, fibrosis, or radiation, or intrinsic because of deep venous thrombosis, surgery, infection, immobility, trauma, or a hypercoagulable state (e.g., protein C deficiency, protein S deficiency, antithrombin 3 deficiency, the presence of neoplasms, or secondary to the venodilating effects of drugs such as calcium channel blockers). (Continued on page 20)
19 Patient with EDEMA
A History Physical examination
I Regional edema
B Generalized edema Check JVP
C JVP normal
Cont’d on p 21
F JVP elevated
Check serum albumin Check urine protein
Chest radiography
G Cardiomegaly
H Normal heart size
Check echocardiogram
Evaluate lung fields
Pericardial effusion
Poor contractibility
Pericarditis/ tamponade
CHF
D Normal serum
Pulmonary hypertension pattern
Clear lung fields Evaluate for pericardial constriction
Evaluate for cor pulmonale
E Decreased serum albumin
albumin
Normal urinalysis
Abnormal urine sediment
Check TFTs
Check BUN/ creatinine Evaluate for renal pathology
Proteinuria
Normal urinalysis
Check 24-hr urine protein 3.5 g protein
3.5 g protein Check LFTs
Normal TFTs
Decreased TFTs
Nephrotic syndrome Abnormal LFTs
Myxedema Evaluate for liver pathology Drug-induced edema
Idiopathic edema
Normal LFTs Check prealbumin and cholesterol
Decreased cholesterol Prealbumin 20 mg/dl
Normal cholesterol Prealbumin 20 mg/dl
Malnutrition Capillary leak
Abnormal protein synthesis
Protein-losing enteropathy
20 J. When regional edema is present, note its location. If it is in one or both upper extremities, determine JVP. K. Patients with upper extremity edema and normal JVP should undergo a Doppler study, impedance plethysmography (IPG), venography, or color flow duplex scanning to look for venous obstruction from either intrinsic or extrinsic causes. A negative study suggests lymphatic obstruction. L. Evaluate patients with upper extremity edema and elevated JVP for superior vena cava syndrome with a chest radiograph, CT scan, or MRI of the chest. M. If the regional edema is confined to the lower extremities, note whether it is unilateral or bilateral. Seek historical features specifically directed toward trauma, a hypercoagulable state, history of neoplasm, or conditions that might cause lymphatic or venous obstruction. N. If the history is negative, order a Doppler study or IPG. If this study is positive, venography may be indicated to evaluate venous thrombosis versus extrinsic compression. If the Doppler study is negative, rhabdomyolysis, musculoskeletal edema, or localized vascular defects may be present.
O. Patients with a positive history of lower extremity edema should undergo IPG, Doppler study, or venography of the lower extremity. Again, a positive study result may suggest venous thrombosis, with treatment for this. A negative study result may suggest lymphatic obstruction. This can be evaluated with lymphangiography. References Berczeller PH. Idiopathic edema. Hosp Pract (Off Ed) 1994;29:115. Braunwald E. Edema. In Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s Principles of Internal Medicine, 14th ed. New York: McGraw-Hill, 1997:210. Ciocon JO, Fernandez BB, Ciocon DG. Leg edema: clinical clues to the differential diagnosis. Geriatrics 1993;48:34. Goroll AH, May LA, Mulley AG. Primary Care Medicine, 3rd ed. Philadelphia: Lippincott-Raven, 1995:105. Greene HL, Kreis SR, Kahn KL. Edema. In Greene HL, ed. Clinical Medicine. 2nd ed. St. Louis: Mosby, 1996:138. Rogers RL, Feller ED, Gottlieb SS. Acute congestive heart failure in the emergency department. Cardiol Clin 2006;24(1):115–123, vii. Schmittling ZC, McLafferty RB, Bohannon WT, et al. Characterization and probability of upper extremity deep venous thrombosis. Ann Vasc Surg 2004;18:552–557. Ware LB, Matthay MA. Clinical practice. Acute pulmonary edema. N Engl J Med 2005;353:2788–2796.
21 Regional edema (Cont’d from p 19)
J
M
Upper extremity Check JVP
K
JVP normal
Noninvasive Vascular Studies or Venography
Negative study
Positive study
Lymphatic obstruction
Venous obstruction
L
Lower extremity Review history
JVP elevated
N
Negative history Doppler study
Chest radiograph, CT scan, or MRI
O
Positive history
Noninvasive Vascular Studies or Venography
Superior vena cava syndrome
Positive study
Negative study
Positive study
Negative study
Venography
Musculoskeletal edema
Venous thrombosis
Lymphatic obstruction
Positive study
Negative study
Venous thrombosis
Extrinsic compression
Venous insufficiency
Edema is an abnormal collection of fluid in the interstitial space that may be localized or generalized. Fluid movement between the intravascular and extravascular space is related to the interacting forces of hydrostatic pressure, colloid oncotic pressure, and capillary permeability and to the effects of lymphatic drainage. Normally there exists an equilibrium among these forces, and no net fluid accumulation takes place. Edema occurs when there is a decrease in plasma oncotic pressure, an increase in hydrostatic pressure, an increase in capillary permeability, or a combination of these factors. Edema also can be present when lymphatic flow is obstructed. A. The history and physical examination focus on the causes of edema and seek to ascertain whether it is generalized or localized. B. Generalized edema can be documented by weight gain and often is associated with increased capillary hydrostatic pressure as seen in congestive heart failure (CHF), in renal failure with increased sodium and water load, after expansion of the intravascular volume from IV fluids, or in conditions of sodium retention. Edema may occur after corticosteroid therapy or with estrogens or other medications. Edema involving the whole body (e.g., anasarca) may extend to involve the peritoneal cavity (e.g., ascites) or the pleural space (e.g., hydrothorax). In patients with generalized edema the first step is to estimate central venous pressure by determining jugular venous pressure (JVP). The distance from the manubrium sterni to the fluid meniscus in the jugular vein should be 2 cm at 45 degrees or 5 cm from the left atrium. C. Determine serum albumin and urinary protein in patients with generalized edema and normal JVP. D. If serum albumin is normal, perform urinalysis, looking for abnormal urinary sediment, and check BUN and creatinine to evaluate the possibility of renal pathology. If urinalysis findings are normal, order thyroid function tests (TFTs) to look for myxedema. Remaining patients
18
E.
F.
G.
H.
I.
should be considered as possibly having idiopathic edema or drug-induced edema. If serum albumin is decreased, perform urinalysis to check for proteinuria. More than 3.5 g protein suggests nephrotic syndrome; 3.5 g in a normal urinalysis suggests another cause, such as hepatitis or hepatic infiltration disease. Order liver function tests (LFTs); if results are abnormal, evaluate for liver pathology. If LFT results are normal, check prealbumin and cholesterol to evaluate for malnutrition. If the prealbumin is 20 mg/dl and the cholesterol level is low, malnutrition is suggested. If the prealbumin is 20 mg/dl, a capillary leak, abnormal protein synthesis, and proteinlosing enteropathy are all possibilities. In patients with an elevated JVP and generalized edema, order chest radiographs to look for cardiomegaly. If cardiomegaly is found, order an echocardiogram to look for pericardial effusion; pericardial thickening, as in acute or chronic pericarditis; abnormal contractility of the heart, as might be seen in CHF; or signs of infiltrative cardiac problems, such as hypertrophic obstructive cardiomyopathy, amyloid, or neoplasm. If cardiac size is normal on the chest film, evaluate the lung fields for pulmonary hypertension. Such a finding should lead to evaluation for cor pulmonale. Clear lung fields should prompt echocardiography to seek pericardial constriction. Regional edema or localized edema often is caused by increased capillary pressure. Some causes include chronic venous insufficiency; incompetent venous valves; vascular obstructions, either extrinsic because of neoplasm, lymph nodes, surgery, fibrosis, or radiation, or intrinsic because of deep venous thrombosis, surgery, infection, immobility, trauma, or a hypercoagulable state (e.g., protein C deficiency, protein S deficiency, antithrombin 3 deficiency, the presence of neoplasms, or secondary to the venodilating effects of drugs such as calcium channel blockers). (Continued on page 20)
19 Patient with EDEMA
A History Physical examination
I Regional edema
B Generalized edema Check JVP
C JVP normal
Cont’d on p 21
F JVP elevated
Check serum albumin Check urine protein
Chest radiography
G Cardiomegaly
H Normal heart size
Check echocardiogram
Evaluate lung fields
Pericardial effusion
Poor contractibility
Pericarditis/ tamponade
CHF
D Normal serum
Pulmonary hypertension pattern
Clear lung fields Evaluate for pericardial constriction
Evaluate for cor pulmonale
E Decreased serum albumin
albumin
Normal urinalysis
Abnormal urine sediment
Check TFTs
Check BUN/ creatinine Evaluate for renal pathology
Proteinuria
Normal urinalysis
Check 24-hr urine protein 3.5 g protein
3.5 g protein Check LFTs
Normal TFTs
Decreased TFTs
Nephrotic syndrome Abnormal LFTs
Myxedema Evaluate for liver pathology Drug-induced edema
Idiopathic edema
Normal LFTs Check prealbumin and cholesterol
Decreased cholesterol Prealbumin 20 mg/dl
Normal cholesterol Prealbumin 20 mg/dl
Malnutrition Capillary leak
Abnormal protein synthesis
Protein-losing enteropathy
20 J. When regional edema is present, note its location. If it is in one or both upper extremities, determine JVP. K. Patients with upper extremity edema and normal JVP should undergo a Doppler study, impedance plethysmography (IPG), venography, or color flow duplex scanning to look for venous obstruction from either intrinsic or extrinsic causes. A negative study suggests lymphatic obstruction. L. Evaluate patients with upper extremity edema and elevated JVP for superior vena cava syndrome with a chest radiograph, CT scan, or MRI of the chest. M. If the regional edema is confined to the lower extremities, note whether it is unilateral or bilateral. Seek historical features specifically directed toward trauma, a hypercoagulable state, history of neoplasm, or conditions that might cause lymphatic or venous obstruction. N. If the history is negative, order a Doppler study or IPG. If this study is positive, venography may be indicated to evaluate venous thrombosis versus extrinsic compression. If the Doppler study is negative, rhabdomyolysis, musculoskeletal edema, or localized vascular defects may be present.
O. Patients with a positive history of lower extremity edema should undergo IPG, Doppler study, or venography of the lower extremity. Again, a positive study result may suggest venous thrombosis, with treatment for this. A negative study result may suggest lymphatic obstruction. This can be evaluated with lymphangiography. References Berczeller PH. Idiopathic edema. Hosp Pract (Off Ed) 1994;29:115. Braunwald E. Edema. In Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s Principles of Internal Medicine, 14th ed. New York: McGraw-Hill, 1997:210. Ciocon JO, Fernandez BB, Ciocon DG. Leg edema: clinical clues to the differential diagnosis. Geriatrics 1993;48:34. Goroll AH, May LA, Mulley AG. Primary Care Medicine, 3rd ed. Philadelphia: Lippincott-Raven, 1995:105. Greene HL, Kreis SR, Kahn KL. Edema. In Greene HL, ed. Clinical Medicine. 2nd ed. St. Louis: Mosby, 1996:138. Rogers RL, Feller ED, Gottlieb SS. Acute congestive heart failure in the emergency department. Cardiol Clin 2006;24(1):115–123, vii. Schmittling ZC, McLafferty RB, Bohannon WT, et al. Characterization and probability of upper extremity deep venous thrombosis. Ann Vasc Surg 2004;18:552–557. Ware LB, Matthay MA. Clinical practice. Acute pulmonary edema. N Engl J Med 2005;353:2788–2796.
21 Regional edema (Cont’d from p 19)
J
M
Upper extremity Check JVP
K
JVP normal
Noninvasive Vascular Studies or Venography
Negative study
Positive study
Lymphatic obstruction
Venous obstruction
L
Lower extremity Review history
JVP elevated
N
Negative history Doppler study
Chest radiograph, CT scan, or MRI
O
Positive history
Noninvasive Vascular Studies or Venography
Superior vena cava syndrome
Positive study
Negative study
Positive study
Negative study
Venography
Musculoskeletal edema
Venous thrombosis
Lymphatic obstruction
Positive study
Negative study
Venous thrombosis
Extrinsic compression
Venous insufficiency