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Mrs. V is 62-year-old woman with leg edema for the past 2 weeks.

image What is the differential diagnosis of edema? How would you frame the differential?


Edema is defined as an increase in the interstitial fluid volume and is generally not clinically apparent until the interstitial volume has increased by at least 2.5–3 L. It is useful to review some background pathophysiology before discussing the differential diagnosis:

  1. Distribution of total body water

    1. 67% intracellular; 33% extracellular

    2. Extracellular water: 25% intravascular; 75% interstitial

  2. Regulation of fluid distribution between the intravascular and interstitial spaces

    1. There is a constant exchange of water and solutes at the arteriolar end of the capillaries.

    2. Fluid is returned from the interstitial space to the intravascular space at the venous end of the capillaries and via the lymphatics.

    3. Movement of fluid from the intravascular space to the interstitium occurs through several mechanisms:

      1. Capillary hydrostatic (hydraulic) pressure pushes fluid out of the vessels.

      2. Interstitial oncotic pressure pulls fluid into the interstitium.

      3. Capillary permeability allows fluid to escape into the interstitium.

    4. Movement of fluid from the interstitium to the intravascular space occurs when opposite pressures predominate.

      1. Intravascular (plasma) oncotic pressure from plasma proteins pulls fluid into the vascular space.

      2. Interstitial hydrostatic pressure pushes fluid out of the interstitium.

    5. In skeletal muscle, the capillary hydrostatic pressure and the intravascular oncotic pressure are the most important factors.

    6. There is normally a small gradient favoring filtration out of the vascular space into the interstitium; the excess fluid is removed via the lymphatic system.

  3. Edema formation occurs when there is

    1. An increase in capillary hydrostatic pressure (for example, increased plasma volume due to renal sodium retention).

    2. An increase in capillary permeability (for example, burns, angioedema).

    3. An increase in interstitial oncotic pressure (for example, myxedema).

    4. A decrease in plasma oncotic pressure (for example, hypoalbuminemia).

    5. Lymphatic obstruction.

Although it is possible to construct a pathophysiologic framework (Figure 17-1) for the differential diagnosis of edema, it is more useful clinically to use the distribution of the edema as the pivotal point:

Figure 17-1.

Pathophysiology of edema. (Adapted with permission from Cho S et al. Peripheral edema. Am J Med. 2002;V113:581. Copyright © 2002 Excerpta Medica, Inc.)

  1. Bilateral leg edema

    1. Due to a systemic cause (with or without presacral edema, ascites, pleural effusion, pulmonary edema, periorbital edema)

      1. Cardiovascular

        • (1) Systolic or diastolic heart failure (HF)

        • (2) Constrictive pericarditis

        • (3) Pulmonary hypertension

      2. Hepatic (cirrhosis)

      3. Renal

        • (1) Advanced kidney disease of any cause

        • (2) Nephrotic syndrome

      4. Hematologic: anemia

        image The most common systemic causes of edema are cardiac, hepatic, and renal diseases.

      5. GI

        • (1) Nutritional deficiency or malabsorption leading to hypoalbuminemia

        • (2) Refeeding edema

      6. Medications

        • (1) Antidepressants: Monoamine oxidase inhibitors

        • (2) Antihypertensives

          • (a) Calcium channel blockers, especially dihydropyridines

          • (b) Direct vasodilators (hydralazine, minoxidil)

          • (c)...

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