Download EDEMA Approximately 60% of lean body weight is water, two

EDEMA
Approximately 60% of lean body weight is water, two-thirds of which is intracellular and the remainder is
in extracellular compartments, mostly as interstitial fluid; only 5% of total body water is in blood plasma.
The term edema signifies increased fluid in the interstitial tissue spaces; fluid collections in different body
cavities are variously designated hydrothorax, hydropericardium, or hydroperitoneum (the last is more
commonly called ascites). Anasarca is a severe and generalized edema with profound subcutaneous
tissue swelling.
There are several pathophysiologic categories of edema (Table 4-1). The mechanism of inflammatory
edema mostly involves increased vascular permeability and is discussed in Chapter 2; noninflammatory
causes of edema are described below.
Increased Hydrostatic Pressure
Impaired venous return
Congestive heart failure
Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or compression
Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with prolonged dependency
Arteriolar dilation
Heat
Neurohumoral dysregulation
Reduced Plasma Osmotic Pressure (Hypoproteinemia)
Protein-losing glomerulopathies (nephrotic syndrome)
Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy
Lymphatic Obstruction
Inflammatory
Neoplastic
Postsurgical
Postirradiation
Sodium Retention
Excessive salt intake with renal insufficiency
Increased tubular reabsorption of sodium
Renal hypoperfusion
Increased renin-angiotensin-aldosterone secretion
Inflammation
Acute inflammation
Chronic inflammation
Angiogenesis
The movement of fluid between vascular and interstitial spaces is controlled mainly by the opposing
effects of vascular hydrostatic pressure and plasma colloid osmotic pressure. Normally, the exit of fluid
into the interstitium from the arteriolar end of the microcirculation is nearly balanced by inflow at the
venular end; the lymphatics drain a small residual amount of excess interstitial fluid. Either increased
capillary pressure or diminished colloid osmotic pressure can result in increased interstitial fluid (Fig. 41). As extravascular fluid accumulates in either case, the increased tissue hydrostatic and plasma osmotic
pressures eventually achieve a new equilibrium, and water re-enters the venules. Excess interstitial edema
fluid is removed by lymphatic drainage, ultimately returning to the bloodstream via the thoracic duct (see
Fig. 4-1); clearly, lymphatic obstruction (e.g., due to scarring or tumor) can also impair fluid drainage and
cause edema. Finally, sodium retention (with its obligatory associated water) due to renal disease can also
cause edema.
The edema fluid occurring with volume or pressure overload, or under conditions of reduced plasma
protein, is typically a protein-poor transudate; it has a specific gravity less than 1.012. Conversely,
because of the increased vascular permeability, inflammatory edema is a protein-rich exudate with a
specific gravity that is usually greater than 1.020 (see Fig. 2-3, Chapter 2).
Increased Hydrostatic Pressure
Localized increases in intravascular pressure can result from impaired venous return; for example, lower
extremity deep venous thrombosis can cause edema restricted to the distal portion of the affected leg.
Generalized increases in venous pressure, with resultant systemic edema, occur most commonly in
congestive heart failure, affecting right ventricular cardiac function. Although increased venous
hydrostatic pressure is contributory, the pathogenesis of cardiac edema is more complex (Fig. 4-2). In
congestive heart failure, reduced cardiac output translates into reduced renal perfusion. Renal
hypoperfusion in turn triggers the renin-angiotensin-aldosterone axis, inducing sodium and water
retention by the kidneys (secondary aldosteronism). This mechanism normally functions to increase
intravascular volume and thereby improve cardiac output to restore normal renal perfusion. However, if
the failing heart cannot increase cardiac output, the extra fluid load causes increased venous pressure and,
eventually, edema. Unless cardiac output is restored or renal water retention reduced (e.g., by salt
restriction, diuretics, or aldosterone antagonists), a cycle of renal fluid retention and worsening edema
ensues. Although salt restriction, diuretics, and aldosterone antagonists are discussed here in the context
of edema in congestive heart failure, it should be understood that they are also of value in the
management of generalized edema resulting from a variety of other causes.
Reduced Plasma Osmotic Pressure
Figure 4-1 Variables affecting fluid transit across capillary walls. Capillary hydrostatic and osmotic forces
are normally balanced so that there is no net loss or gain of fluid across the capillary bed. However,
increased hydrostatic pressure or diminished plasma osmotic pressure leads to a net accumulation of
extravascular fluid (edema). As the interstitial fluid pressure increases, tissue lymphatics remove much of
the excess volume, eventually returning it to the circulation via the thoracic duct. If the ability of the
lymphatics to drain tissue fluid is exceeded, persistent tissue edema results.
Figure 4-2 Pathways leading to systemic edema due to primary heart failure, primary renal failure, or
reduced plasma osmotic pressure (e.g., from malnutrition, diminished hepatic synthesis, or protein loss
due to the nephrotic syndrome). ADH, antidiuretic hormone; GFR, glomerular filtration rate.
Albumin is the serum protein most responsible for maintaining intravascular colloid osmotic pressure;
reduced osmotic pressure occurs when albumin is inadequately synthesized or is lost from the circulation.
An important cause of albumin loss is the nephrotic syndrome (Chapter 14), in which glomerular capillary
walls become leaky; patients typically present with generalized edema. Reduced albumin synthesis occurs
in the setting of diffuse liver diseases (e.g., cirrhosis; Chapter 16) or due to protein malnutrition (Chapter
8). In each case, reduced plasma osmotic pressure leads to a net movement of fluid into the interstitial
tissues with subsequent plasma volume contraction. Predictably, reduced intravascular volume leads to
renal hypoperfusion followed by secondary aldosteronism. Unfortunately, the retained salt and water
cannot correct the plasma volume deficit since the primary defect of low serum proteins persists. As with
congestive heart failure, edema precipitated by low protein is exacerbated by secondary salt and fluid
retention.
Lymphatic Obstruction
Impaired lymphatic drainage and consequent lymphedema is usually localized; it can result from
inflammatory or neoplastic obstruction. For example, the parasitic infection filariasis can cause extensive
inguinal lymphatic and lymph node fibrosis. The resultant edema of the external genitalia and lower limbs
can be so massive as to earn the appellation elephantiasis. Cancer of the breast can be treated by resection
and/or irradiation of the associated axillary lymph nodes; the resultant scarring and loss of lymphatic
drainage can cause severe upper extremity edema. In breast carcinoma infiltration and obstruction of
superficial lymphatics can also cause edema of the overlying skin, the so-called peau d'orange (orange
peel) appearance. Such a finely pitted surface results from an accentuation of depressions in the skin at
the site of hair follicles.
Sodium and Water Retention
Salt retention can also be a primary cause of edema. Increased salt-with the obligate accompanying watercauses both increased hydrostatic pressure (due to expansion of the intravascular volume) and reduced
vascular osmotic pressure. Salt retention can occur with any compromise of renal function, as in
poststreptococcal glomerulonephritis and acute renal failure.
SUMMARY
Edema is extravasation of fluid from vessels into interstitial spaces; the fluid may be protein poor
(transudate) or may be protein rich (exudate).Edema results from any of the following conditions:
Increased hydrostatic pressure, caused by a reduction in venous return (as in heart failure)Decreased
colloid osmotic pressure, caused by reduced concentration of plasma albumin (due to decreased synthesis,
as in liver disease, or increased loss, as in kidney disease)Lymphatic obstruction that impairs interstitial
fluid clearance (as in scarring, tumors, or certain infections)Primary renal sodium retention (in renal
failure)Increased vascular permeability (in inflammation)
Morphology
Edema is most easily recognized grossly; microscopically, edema fluid is reflected primarily as a clearing
and separation of the extracellular matrix elements with subtle cell swelling. Although any organ or tissue
in the body may be involved, edema is most commonly encountered in subcutaneous tissues, lungs, and
brain.
Subcutaneous edema can be diffuse or more prominent in regions with high hydrostatic pressures; the
ultimate distribution depends on the underlying etiology. Even diffuse edema is usually more prominent
in certain body areas as a result of the effects of gravity; a gravity-dependent distribution is referred to as
dependent edema (e.g., involving the legs when standing, or involving the sacrum when recumbent).
Dependent edema is a prominent feature of cardiac failure, particularly of the right ventricle.
Edema due to renal dysfunction or nephrotic syndrome is generally more severe than cardiac edema
and affects all parts of the body equally. Nevertheless, severe edema early in the disease course can still
manifest disproportionately in tissues with a loose connective tissue matrix (e.g., the eyelids, causing
periorbital edema). Finger pressure over significantly edematous subcutaneous tissue displaces the
interstitial fluid and leaves a finger-shaped depression, so-called pitting edema.
Pulmonary edema is a common clinical problem most frequently seen in the setting of left ventricular
failure (with a dependent distribution in the lungs), but it also occurs in renal failure, acute respiratory
distress syndrome (ARDS; Chapter 13), pulmonary infections, and hypersensitivity reactions. The lungs
typically weigh two to three times their normal weight, and sectioning reveals frothy, sometimes bloodtinged fluid representing a mixture of air, edema fluid, and extravasated red cells.
Edema of the brain may be localized to sites of focal injury (e.g., infarct, abscesses or neoplasms) or
may be generalized, as in encephalitis, hypertensive crises, or obstruction to the brain's venous outflow.
Trauma may result in local or generalized edema, depending on the nature and extent of the injury. With
generalized edema, the brain is grossly swollen with narrowed sulci and distended gyri showing signs of
flattening against the unyielding skull.
Clinical Correlation
The effects of edema may range from merely annoying to rapidly fatal. Subcutaneous tissue edema in
cardiac or renal failure is important primarily because it indicates underlying disease; however, when
significant it can also impair wound healing or the clearance of infection. In contrast, pulmonary edema
can cause death by interfering with normal ventilatory function. Not only does fluid collect in the alveolar
septa around capillaries and impede oxygen diffusion, but edema fluid in the alveolar spaces also creates
a favorable environment for bacterial infection. Brain edema is serious and can be rapidly fatal. If severe,
brain edema can cause herniation (extrusion of the brain) through the foramen magnum; the brainstem
vascular supply can also be compressed by edema causing increased intracranial pressure. Either state can
injure the medullary centers and can cause death.