Into The Interstitial Space
Peripheral edema is an accumulation of fluid in the interstitial space that occurs when capillary filtration exceeds lymphatic drainage. Forces that can lead to edema include alterations in hydrostatic pressure and oncotic pressure, increased capillary permeability, and lymphatic obstruction.

- Fun facts:
- Peripheral edema does not become clinically apparent until the interstitial volume has increased by at least 2.5-3 liters.
- Capillary hydraulic pressure is relatively insensitive to alterations in arterial pressure, owing to the autoregulatory changes at the precapillary sphincter. For instance, the sphincter constricts in the presence of increased arterial pressure, minimizing the elevation in capillary hydraulic pressure and preventing the development of edema.
- Fluid entry into the interstitium will eventually raise the interstitial hydraulic pressure, reducing the pressure gradient favoring filtration.
- Lymphatic obstruction is an unusual cause of edema, known as lymphedema. It most often results from radical lymph node dissection for malignancy (e.g., breast cancer.)
H&P
Key components of the history:
- Timing: acute vs chronic
- Acute (<72 hours): Consider DVT, cellulitis, acute compartment syndrome, recent initiation of calcium channel blockers
- Chronic: Consider heart failure, renal disease, liver disease
- Location and distribution: unilateral vs bilateral, localized vs generalized
- Unilateral: Consider DVT, venous insufficiency, lymphatic obstruction, lymphatic destruction
- Bilateral: Consider heart failure, pulmonary hypertension, renal disease, liver disease
- Positionality:
- Better with elevation and worse with dependency: Consider venous insufficiency
- No change with dependency: Consider etiologies associated with decreased oncotic pressure such as liver failure, nephrotic syndrome, malabsorption
- Other: associated symptoms, skin changes, pain, medication use, recent travel
Potential exam findings:
- Inspection: skin discoloration/lesions, asymmetry
- Palpation: temperature (cool/warm), tenderness, pitting vs non-pitting
- Pitting occurs when fluid in the interstitial space has a low concentration of protein, which is associated with decreased oncotic pressure. Pitting severity is graded on a 4-point scale, which unfortunately is not standardized.
The above exam findings focus on peripheral edema itself. Obviously other components of the exam are pertinent in determining the etiology of edema: cardiovascular, pulmonary, abdominal, skin, etc.
Diagnostic Frameworks
Considering the above history and exam findings, we can build a differential diagnosis for peripheral edema based on specific characteristics.
Timing and location:

Similarly, we can also build a framework according to the underlying mechanism:

Blog post based on Med-Peds Forum talk by Ruth Cadet, PGY3, and Ashley Nguyen, PGY4