A. Body Fluid Composition

1. Total body water is 60% of weight
   1. 2/3 of that is Intracellular (40% of weight overall)
   2. 1/3 of that is extracellular (20% of weight overall)
2. Extracellular water is divided into:
   1. Interstitial (extravascular) water: 75% of extracellular water (~15% overall)
   2. Intravascular (Plasma) water: 25% of extracellular water (~5% overall)
3. Typical blood volume in a human is 5-6 Liters (L)
   1. ~50% overall is formed elements (mainly red blood cells)
   2. ~50% is plasma (~3 L in most patients)

B. Balance Between Fluid Compartments

1. First determined by Starling
2. Intravascular and extravascular fluid movement depend on:
   1. Hydrostatic pressure gradient
   2. Oncotic pressure gradient
   3. Permeability of blood vessels
3. Hydrostatic pressure gradient
   1. Blood pressure (capillary or venous pressure in most cases)
   2. Interstitial pressure
4. Oncotic pressure
   1. Plasma proteins (mainly albumin)
   2. Interstitial components (mainly mucopolyscaccharides and filtered proteins)
5. Plasma Oncotic Pressure
   1. Total 28mm 7.3g/dL
   2. Albumin 21mm 4.5g/dL
   3. Globulins 6.5mm 2.5g/dL
   4. Fibrinogen 0.3mm 0.3g/dL
   5. Plasma Osmolality 280-300 mOsm
6. Lymphatic system
   1. Collects fluid and proteins from interstitial space
   2. Returns them to vascular compartment

C. Formation of Edema

1. Occurs when
   1. Starling forces become substantially unbalanced
   2. Lymphatic system cannot remove fluid
2. Obvious (pitting) edema typically requires >10% of body weight accumulation of fluid
   1. Plasma volume is ~3L; 10% body weight ~8L
   2. Thus, in order to develop edema, kidney must retain water (H2O) and sodium (Na)
3. Role of Kidney
   1. Kidney maintains effective intravascular volume to preserve hemodynamics
   2. Elevated angiotensin II, aldosterone, antidiuretic hormone (ADH, vasopressin)
   3. Renal insensitivity to natriuretic factors also contributes to fluid accumulation
   4. Intravascular volume/pressure depletion stimulates renal Na and H20 retention
   5. Many edematous states associated with intravascular volume/pressure depletion
   6. Cardiac insufficiency (heart failure, constriction, restriction) most commonly involved
4. Other Mechanisms of Fluid Retention
   1. Reduced plasma oncotic pressure (hypoalbuminemia)
   2. Venous (peripheral, central, portal) obstruction
   3. Lymphatic obstruction
   4. Renal failure (oliguria, anuria)
5. Anasarca is total body edema usually associated with severe hypoalbuminemia
6. Determination of cause is critically important to treatment
   1. Good history and physical
   2. Characterization and progression of edema (0 to 4+ pitting qualitatively)
   3. Lower extremity edema also characterized by distance above ankle
   4. Other tests as directed by differential below

D. Bilateral versus Unilateral Edema

1. Bilateral edema is usually indicative of systemic (versus local) process
2. Cardiac Insufficiency is usually bilateral [1]
   1. Left ventricular systolic dysfunction is most common cardiac cause
   2. Diastolic Dysfunction is not uncommon
   3. Atrial fibrillation is third most common
   4. Restrictive or constrictive cardiomyopathy
3. Pulmonary dysfunction including pulmonary hypertension is often bilateral
4. Portal Hypertension may show Right > Left lower extremity edema
5. Unilateral is usually due to obstruction of venous or lymphatic return
   1. Venous Obstruction - deep vein thrombosis most common
   2. Lymphatic Obstruction - malignancy or infection
   3. Venous Insuffiency - usually after harvest of vein graft or chronic deep vein thrombosis

E. Drugs

1. Calcium channel blockers: Dihydropyridine more than others
2. Direct vasodilators
3. Antihypertensive agents
4. Minoxidil, diazoxide, hydralazine
5. Estrogen/progesterone
6. Testosterone
7. Glucocorticoids
8. NSAIDs (nonspecific and COX2 selective)
9. Glitazones
10. Phenylbutazone
11. Monoamine oxidase inhibitors (MAO-I)
12. Antidepressants
13. Usually cause bilateral lower extremity edema

F. Hypoalbuminemia (Hypoproteinemia)

1. Nephrotic Syndrome
   1. Hypoalbuminemia
   2. Albuminuria
   3. Frequently present with true anasarca
2. Failure of Albumin Synthesis
   1. Hepatic Failure
   2. Protein Malabsorption
   3. Malnutrition with hypoproteinemia

G. Soft Tissue Swelling

1. Myxedema (usually with hypothyroidism)
2. Lymphatic Insufficiency
   1. Lymphedema
   2. Described as woody or brawny
3. Scleroderma
   1. Mainly begins on hands, feet
   2. Spreads proximally
4. Scleredema - on back and shoulders
5. Fasciitis - infectious, eosinophilic

H. Other Fluid Retention

1. Pregnancy
2. Chronic venous insufficiency - congenital or acquired
3. Idiopathic edema

References

1. Cho S and Atwood E. 2002. Am J Med. 113(7):580
2. Blankfield RP, Finkelhor RS, Alexander JJ, et al. 1998. Am J Med. 105(3):192