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.
he term edema signifies increased fluid in the interstitial tissue spaces; fluid collections in different body
ca!ities are !ariously designated hydrothorax, hydropericardium, or hydroperitoneum "the last is more
commonly called ascites#. Anasarca is a se!ere and generali$ed edema with profound subcutaneous
tissue swelling.
here are se!eral pathophysiologic categories of edema "able %-&#. he mechanism of inflammatory
edema mostly in!ol!es increased !ascular permeability and is discussed in 'hapter (; noninflammatory
causes of edema are described below.
Increased Hydrostatic Pressure
)mpaired !enous return
'ongesti!e heart failure
'onstricti!e pericarditis
Ascites "li!er cirrhosis#
*enous obstruction or compression
hrombosis
+xternal pressure "e.g., mass#
,ower extremity inacti!ity with prolonged dependency
Arteriolar dilation
-eat
.eurohumoral dysregulation
Reduced Plasma Osmotic Pressure (Hypoproteinemia)
/rotein-losing glomerulopathies "nephrotic syndrome#
,i!er cirrhosis "ascites#
0alnutrition
/rotein-losing gastroenteropathy
Lymphatic Obstruction
)nflammatory
.eoplastic
/ostsurgical
/ostirradiation
Sodium Retention
+xcessi!e salt inta1e with renal insufficiency
)ncreased tubular reabsorption of sodium
2enal hypoperfusion
)ncreased renin-angiotensin-aldosterone secretion
Inlammation
Acute inflammation
'hronic inflammation
Angiogenesis
he mo!ement of fluid between !ascular and interstitial spaces is controlled mainly by the opposing
effects of !ascular hydrostatic pressure and plasma colloid osmotic pressure. .ormally, the exit of fluid
into the interstitium from the arteriolar end of the microcirculation is nearly balanced by inflow at the
!enular end; the lymphatics drain a small residual amount of excess interstitial fluid. +ither increased
capillary pressure or diminished colloid osmotic pressure can result in increased interstitial fluid "3ig. %-
&#. As extra!ascular fluid accumulates in either case, the increased tissue hydrostatic and plasma osmotic
pressures e!entually achie!e a new e4uilibrium, and water re-enters the !enules. +xcess interstitial edema
fluid is remo!ed by lymphatic drainage, ultimately returning to the bloodstream !ia the thoracic duct "see
3ig. %-&#; clearly, lymphatic obstruction "e.g., due to scarring or tumor# can also impair fluid drainage and
cause edema. 3inally, sodium retention "with its obligatory associated water# due to renal disease can also
cause edema.
he edema fluid occurring with !olume or pressure o!erload, or under conditions of reduced plasma
protein, is typically a protein-poor transudate; it has a specific gra!ity less than &.0&(. 'on!ersely,
because of the increased !ascular permeability, inflammatory edema is a protein-rich exudate with a
specific gra!ity that is usually greater than &.0(0 "see 3ig. (-5, 'hapter (#.
Increased Hydrostatic Pressure
Localized increases in intra!ascular pressure can result from impaired !enous return; for example, lower
extremity deep !enous thrombosis can cause edema restricted to the distal portion of the affected leg.
Generalized increases in !enous pressure, with resultant systemic edema, occur most commonly in
congestive heart failure, affecting right !entricular cardiac function. Although increased !enous
hydrostatic pressure is contributory, the pathogenesis of cardiac edema is more complex "3ig. %-(#. )n
congesti!e heart failure, reduced cardiac output translates into reduced renal perfusion. 2enal
hypoperfusion in turn triggers the renin-angiotensin-aldosterone axis, inducing sodium and water
retention by the 1idneys (secondary aldosteronism#. his mechanism normally functions to increase
intra!ascular !olume and thereby impro!e cardiac output to restore normal renal perfusion. -owe!er, if
the failing heart cannot increase cardiac output, the extra fluid load causes increased !enous pressure and,
e!entually, edema. 6nless 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 congesti!e heart failure, it should be understood that they are also of !alue in the
management of generali$ed edema resulting from a !ariety of other causes.
Reduced Plasma Osmotic Pressure
3igure %-& *ariables affecting fluid transit across capillary walls. 'apillary hydrostatic and osmotic
forces are normally balanced so that there is no net loss or gain of fluid across the capillary bed. -owe!er,
increased hydrostatic pressure or diminished plasma osmotic pressure leads to a net accumulation of
extra!ascular fluid "edema#. As the interstitial fluid pressure increases, tissue lymphatics remo!e much of
the excess !olume, e!entually returning it to the circulation !ia the thoracic duct. )f the ability of the
lymphatics to drain tissue fluid is exceeded, persistent tissue edema results.
3igure %-( /athways 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#. A7-, antidiuretic hormone; 832, glomerular filtration rate.
Albumin is the serum protein most responsible for maintaining intra!ascular colloid osmotic pressure;
reduced osmotic pressure occurs when albumin is inade4uately synthesi$ed or is lost from the circulation.
An important cause of albumin loss is the nephrotic syndrome "'hapter &%#, in which glomerular
capillary walls become lea1y; patients typically present with generali$ed edema. 2educed albumin
synthesis occurs in the setting of diffuse li!er diseases "e.g., cirrhosis; 'hapter &6# or due to protein
malnutrition "'hapter 9#. )n each case, reduced plasma osmotic pressure leads to a net mo!ement of fluid
into the interstitial tissues with subse4uent plasma !olume contraction. /redictably, reduced intra!ascular
!olume leads to renal hypoperfusion followed by secondary aldosteronism. 6nfortunately, the retained
salt and water cannot correct the plasma !olume deficit since the primary defect of low serum proteins
persists. As with congesti!e heart failure, edema precipitated by low protein is exacerbated by secondary
salt and fluid retention.
Lymphatic Obstruction
)mpaired lymphatic drainage and conse4uent lymphedema is usually locali$ed; it can result from
inflammatory or neoplastic obstruction. 3or example, the parasitic infection filariasis can cause extensi!e
inguinal lymphatic and lymph node fibrosis. he resultant edema of the external genitalia and lower limbs
can be so massi!e as to earn the appellation elephantiasis. 'ancer of the breast can be treated by resection
and:or irradiation of the associated axillary lymph nodes; the resultant scarring and loss of lymphatic
drainage can cause se!ere upper extremity edema. )n breast carcinoma infiltration and obstruction of
superficial lymphatics can also cause edema of the o!erlying s1in, the so-called peau d'orange "orange
peel# appearance. ;uch a finely pitted surface results from an accentuation of depressions in the s1in at
the site of hair follicles.
Sodium and !ater Retention
;alt retention can also be a primary cause of edema. )ncreased salt-with the obligate accompanying water-
causes both increased hydrostatic pressure "due to expansion of the intra!ascular !olume# and reduced
!ascular osmotic pressure. ;alt retention can occur with any compromise of renal function, as in
poststreptococcal glomerulonephritis and acute renal failure.
S"MMAR#
+dema is extra!asation of fluid from !essels into interstitial spaces; the fluid may be protein poor
"transudate# or may be protein rich "exudate#.+dema results from any of the following conditions<
)ncreased hydrostatic pressure, caused by a reduction in !enous return "as in heart failure#7ecreased
colloid osmotic pressure, caused by reduced concentration of plasma albumin "due to decreased synthesis,
as in li!er disease, or increased loss, as in 1idney disease#,ymphatic obstruction that impairs interstitial
fluid clearance "as in scarring, tumors, or certain infections#/rimary renal sodium retention "in renal
failure#)ncreased !ascular permeability "in inflammation#
Morpholo$y
+dema is most easily recogni$ed grossly; microscopically, edema fluid is reflected primarily as a clearing
and separation of the extracellular matrix elements with subtle cell swelling. Although any organ or tissue
in the body may be in!ol!ed, edema is most commonly encountered in subcutaneous tissues, lungs, and
brain.
Subcutaneous edema can be diffuse or more prominent in regions with high hydrostatic pressures; the
ultimate distribution depends on the underlying etiology. +!en diffuse edema is usually more prominent
in certain body areas as a result of the effects of gra!ity; a gra!ity-dependent distribution is referred to as
dependent edema "e.g., in!ol!ing the legs when standing, or in!ol!ing the sacrum when recumbent#.
Dependent edema is a prominent eature o cardiac ailure% particularly o the ri$ht &entricle.
+dema due to renal dysunction or nephrotic syndrome is generally more se!ere than cardiac edema
and aects all parts o the body e'ually. .e!ertheless, se!ere edema early in the disease course can still
manifest disproportionately in tissues with a loose connecti!e tissue matrix "e.g., the eyelids, causin$
periorbital edema#. 3inger pressure o!er significantly edematous subcutaneous tissue displaces the
interstitial fluid and lea!es a finger-shaped depression, so-called pittin$ edema(
Pulmonary edema is a common clinical problem most fre4uently seen in the setting of left !entricular
failure "with a dependent distribution in the lungs#, but it also occurs in renal failure, acute respiratory
distress syndrome "A27;; 'hapter &5#, pulmonary infections, and hypersensiti!ity reactions. he lungs
typically weigh two to three times their normal weight, and sectioning re!eals frothy, sometimes blood-
tinged fluid representing a mixture of air, edema fluid, and extra!asated red cells.
Edema o the brain may be locali$ed to sites of focal in=ury "e.g., infarct, abscesses or neoplasms# or
may be generali$ed, as in encephalitis, hypertensi!e crises, or obstruction to the brain>s !enous outflow.
rauma may result in local or generali$ed edema, depending on the nature and extent of the in=ury. ?ith
generali$ed edema, the brain is grossly swollen with narrowed sulci and distended gyri showing signs of
flattening against the unyielding s1ull.
)linical )orrelation
he effects of edema may range from merely annoying to rapidly fatal. ;ubcutaneous tissue edema in
cardiac or renal failure is important primarily because it indicates underlying disease; howe!er, when
significant it can also impair wound healing or the clearance of infection. )n contrast, pulmonary edema
can cause death by interfering with normal !entilatory function. .ot only does fluid collect in the al!eolar
septa around capillaries and impede oxygen diffusion, but edema fluid in the al!eolar spaces also creates
a fa!orable en!ironment for bacterial infection. @rain edema is serious and can be rapidly fatal. )f se!ere,
brain edema can cause herniation "extrusion of the brain# through the foramen magnum; the brainstem
!ascular supply can also be compressed by edema causing increased intracranial pressure. +ither state can
in=ure the medullary centers and can cause death.