EDEMA

Dr. Bernardo Dámaso Mata

 EDEMA
INTRODUCTION
Edema is defined as a palpable swelling produced by expansion of the
interstitial fluid volume. A variety of clinical conditions are associated
with the development of edema, including heart failure, cirrhosis, and
the nephrotic syndrome.
Some patients have localized edema. This can be caused by a variety of
conditions, including venous obstruction, as occurs with deep vein
thrombosis or venous stasis, and allergic reactions (such as laryngeal
edema).
EDEMA
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Major causes of edema by primary mechanism

Increased capillary hydraulic pressure

A. Increased plasma volume due to renal Na+ retention

1. Heart failure, including cor pulmonale
2. Primary renal sodium retention
a. Renal disease, including the nephrotic syndrome
b. Drugs: minoxidil, diazoxide, thiazolidinediones, calcium channel blockers
(particularly nifedipine), nonsteroidal anti-inflammatory drugs, fludrocortisone,
estrogens
c. Refeeding edema
d. Early hepatic cirrhosis
3. Pregnancy and premenstrual edema
4. Idiopathic edema, when diuretic induced

B. Venous obstruction
1. Cirrhosis or hepatic venous obstruction
2. Acute pulmonary edema
3. Local venous obstruction
 EDEMA
Major causes of edema by primary mechanism

Increased capillary hydraulic pressure

C. Decreased arteriolar resistance

1. Calcium channel blockers (?)
2. Idiopathic edema (?)
 EDEMA
Major causes of edema by primary mechanism

Hypoalbuminemia

A. Protein loss
1. Nephrotic syndrome
2. Protein-losing enteropathy
B. Reduced albumin synthesis
1. Liver disease
2. Malnutrition
 EDEMA
Major causes of edema by primary mechanism

Increased capillary permeability

A. Idiopathic edema (?)

B. Burns
C. Trauma
D. Inflammation or sepsis
E. Allergic reactions, including certain forms of angioedema
F. Adult respiratory distress syndrome
G. Diabetes mellitus
H. Interleukin-2 therapy
I. Malignant ascites
 EDEMA
Major causes of edema by primary mechanism

Lymphatic obstruction or increased interstitial oncotic pressure

A. Lymph node dissection

B. Nodal enlargement due to malignancy
C. Hypothyroidism
D. Malignant ascites

Uncertain mechanism

A. Docetaxel
B. Pramipexole
EDEMA
 EDEMA
PATHOPHYSIOLOGY OF EDEMA FORMATION
There are two basic steps involved in edema formation:
• An alteration in capillary hemodynamics that favors the movement
of fluid from the vascular space into the interstitium.
• The retention of dietary or intravenously administered sodium and
water by the kidneys.
 EDEMA
PATHOPHYSIOLOGY OF EDEMA FORMATION
The importance of the kidneys in the development of edema should
not be underestimated.
Edema (other than localized edema as with an allergic reaction) does
not become clinically apparent until the interstitial volume has
increased by at least 2.5 to 3 liters.
Since the normal plasma volume is only about 3 liters, it is clear that
patients would develop marked hemoconcentration and shock if the
edema fluid were derived only from the plasma.
 EDEMA
PATHOPHYSIOLOGY OF EDEMA FORMATION
Hemoconcentration and shock do not occur because of the following
sequence:
• The initial movement of fluid from the vascular space into the
interstitium reduces the plasma volume and consequently tissue
perfusion.
• In response to these changes, the kidney retains sodium and water.
• Some of this fluid stays in the vascular space, returning the plasma
volume toward normal. However, the alteration in capillary
hemodynamics results in most of the retained fluid entering the
interstitium and eventually becoming apparent as edema
 EDEMA
PATHOPHYSIOLOGY OF EDEMA FORMATION
The net effect is a marked expansion of the total extracellular volume
(as edema) with maintenance of the plasma volume at closer-to-
normal levels.
This pathophysiologic sequence also illustrates an important point that
must be considered when treating a patient with edema.
 EDEMA
PATHOPHYSIOLOGY OF EDEMA FORMATION
Renal sodium and water retention in most edematous states is an
appropriate compensation in that it restores tissue perfusion, even
though it also augments the degree of edema.
Removing the edema fluid with diuretic therapy will improve
symptoms due to edema but may diminish tissue perfusion,
occasionally to clinically significant levels.
 EDEMA
The hemodynamic effects are different when the primary abnormality
is inappropriate renal fluid retention.
In this setting, both the plasma and interstitial volumes are expanded,
and deleterious hemodynamic effects from removal of the excess fluid
are much less likely.
This is an example of overfilling of the vascular tree which most often
occurs with primary renal disease.
 EDEMA
Capillary hemodynamics — The exchange of fluid between the plasma
and the interstitium is determined by the hydraulic and oncotic
pressures in each compartment.
The relationship between these parameters can be expressed by
Starling's law:
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where Lp is the unit permeability (or porosity) of the capillary wall, S is
the surface area available for fluid movement, Pcap and Pif are the
capillary and interstitial fluid hydraulic pressures, πcap and πif are the
capillary and interstitial fluid oncotic pressures, and s represents the
reflection coefficient of proteins across the capillary wall (with values
ranging from 0 if completely permeable to 1 if completely
impermeable).
The interstitial oncotic pressure is derived primarily from plasma
proteins that have crossed from the capillary to the interstitium and, to
a lesser degree, proteoglycans, which originate in the interstitium.
 EDEMA
The mean capillary hydraulic pressure (17 mmHg), which pushes fluid
out of the capillary, and the plasma oncotic pressure (28 mmHg), which
pulls fluid back into the capillary, are quantitatively the most
important.
There is normally a small mean gradient of about 0.3 mmHg favoring
filtration out of the vascular space; the fluid that is filtered is then
returned to the systemic circulation by the lymphatics so that fluid
accumulation in the interstitium is prevented.
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Starling's forces are substantially different in some other organs, such
as the liver. The hepatic sinusoids are highly permeable to proteins; as
a result, the capillary and interstitial oncotic pressures are roughly
equal, and there is little transcapillary oncotic pressure gradient.
 EDEMA
The net effect is that the hydraulic pressure gradient favoring filtration
is essentially unopposed. To some degree, filtration is minimized by a
lower capillary hydraulic pressure than in skeletal muscle since
approximately two-thirds of hepatic blood flow is derived from the
portal vein, a low-pressure system.
In addition, ascites does not normally develop because the filtered
fluid is removed by the lymphatics.
 EDEMA
The alveolar capillaries also have a relatively low capillary hydraulic
pressure (due to perfusion from the low-pressure system in the right
ventricle) and are more permeable than skeletal muscle to proteins.
This results in smaller transcapillary hydraulic and oncotic pressure
gradients.
 EDEMA
Edema formation
The development of edema requires an alteration in one or more of
the Starling forces in a direction that favors an increase in net filtration
and also inadequate removal of the additional filtered fluid by
lymphatic drainage.
EDEMA
 EDEMA
Edema formation
Edema may form in response to an elevation in capillary hydraulic
pressure (which increases the "Δ hydraulic pressure"), increased
capillary permeability (Lp), higher interstitial oncotic pressure, a lower
plasma oncotic pressure (which reduces the "Δ oncotic pressure"), or a
combination of these changes.
Edema can also be induced by lymphatic obstruction since the fluid
that is normally filtered is not returned to the systemic circulation.
EDEMA
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Increased capillary hydraulic pressure
Capillary hydraulic pressure, although generated by cardiac
contraction, is relatively insensitive to alterations in arterial pressure.
This stability is due to autoregulatory changes in resistance at the
precapillary sphincter, which determine the extent to which the
arterial pressure is transmitted to the capillary.
If the arterial pressure is increased, for example, the sphincter
constricts, minimizing the elevation in capillary hydraulic pressure and
preventing the development of edema.
EDEMA
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Increased capillary hydraulic pressure
In contrast, the resistance at the venous end of the capillary is not well
regulated. Consequently, changes in venous pressure result in parallel
alterations in capillary hydraulic pressure. The venous pressure is
increased in two settings:
(1) when the blood volume is expanded, augmenting the volume in
the venous system, and
(2) when there is venous obstruction.
 EDEMA
Increased capillary hydraulic pressure
Examples of edema due to volume expansion include heart failure and
renal disease; edema due to effective venous obstruction is commonly
seen with cirrhosis of the liver, in which there is a marked increase in
hepatic sinusoidal pressure, and with deep venous thrombosis in the
lower extremities.
Diastolic dysfunction due to decreased compliance of the heart (which
results in pulmonary edema) and right heart failure and pericardial
disease (which result in peripheral edema) are other causes of
effective venous obstruction.
 EDEMA
Hypoalbuminemia
Hypoalbuminemia due to albumin loss in the urine in the nephrotic
syndrome or to decreased hepatic albumin synthesis also contributes
to edema formation. However, chronic hypoalbuminemia alone may be
insufficient to induce edema.
 EDEMA
Increased capillary permeability
An increase in capillary permeability due to vascular injury promotes
the development of edema for several reasons.
– With vascular injury, the unit permeability (porosity, or "Lp" in
the equation above) of the capillary wall increases, which tends
to increase net filtration.
– In addition, the reflection coefficient of proteins across the
capillary wall ("s" in the equation above) decreases, and the
movement of albumin from the vascular space into the
interstitium narrows the difference between the capillary and
interstitial oncotic pressures ("ncap" and "nif"), thereby reducing
the oncotic pressure gradient.
 EDEMA
Increased capillary permeability
Increased capillary permeability contributes to edema in the following
clinical settings:
• Burns, in which both histamine and oxygen free radicals can induce
microvascular injury in addition to the direct physical action of the
injury.
• Therapy with recombinant human interleukin-2 or vascular
endothelial growth factor, which appear to directly increase
capillary permeability.
 EDEMA
Increased capillary permeability
Increased capillary permeability contributes to edema in the following
clinical settings:
• Episodic idiopathic capillary leak syndromes, which may be
mediated by increased expression of interleukin-2 receptors on
circulating mononuclear cells or by increased generation of kinins.
 EDEMA
Increased capillary permeability
Increased capillary permeability contributes to edema in the following
clinical settings:
• Any of the conditions associated with the adult respiratory distress
syndrome. In this disorder, ischemia- or sepsis-induced release of
cytokines, such as interleukin-1 or tumor necrosis factor, may play
an important role in the increase in pulmonary capillary
permeability, at least in part via the recruitment of neutrophils.
 EDEMA
Increased capillary permeability
Increased capillary permeability contributes to edema in the following
clinical settings:
• Capillary permeability is moderately increased in patients with
diabetes mellitus. This abnormality may be mediated in part by
hyperglycemia-induced accumulation of advanced glycosylation end
products derived from the combination of glucose with circulating
proteins. The net effect is to enhance the severity of edema which,
in these patients, is usually due to heart failure or the nephrotic
syndrome.
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Increased capillary permeability
Increased capillary permeability contributes to edema in the following
clinical settings:
• The malnutrition syndrome, kwashiorkor, may be another example
of edema due in part to increased capillary permeability. Although
edema has often been ascribed to hypoalbuminemia, increased
generation of cysteinyl leukotrienes that increase capillary
permeability may be of primary importance in the edema of
kwashiorkor.
 EDEMA
Lymphatic obstruction (lymphedema)
Lymphatic obstruction is an unusual cause of edema (called
lymphedema).
It is most often due to radical lymph node dissection for malignancy
(eg, breast cancer).
Lymphatic obstruction may also play a pivotal role in the development
of "nephrogenic ascites".
 EDEMA
Myxedema
Hypothyroidism leads to a marked accumulation of interstitial albumin
and other proteins. Although this may be due in part to an elevation in
capillary protein permeability, the excess interstitial protein and fluid
would normally be returned to the systemic circulation by the
lymphatics.
 EDEMA
Myxedema
However, lymphatic flow is low or normal in patients with myxedema
and not increased as in other edematous states. This may be due to
binding of the filtered proteins to excess interstitial
mucopolysaccharides, thereby preventing their removal by the
lymphatics.
 EDEMA
Compensatory factors
Since there is normally a small gradient favoring filtration, it might be
expected that only a minor change in these hemodynamic forces
would lead to edema.
However, experimental and clinical observations indicate that there
must be at least a 15 mmHg increase in the gradient favoring filtration
before edema can be detected.
 EDEMA
Compensatory factors
Three factors contribute to this protective response.
• Lymphatic flow and contractility increase in the presence of tissue
edema and remove some of the excess filtrate.
• Fluid entry into the interstitium will eventually raise the interstitial
hydraulic pressure, reducing the pressure gradient favoring
filtration.
• Fluid entry into the interstitium also lowers the interstitial oncotic
pressure, both by dilution and by lymphatic-mediated removal of
interstitial proteins.
 EDEMA
Compensatory factors
• The reduction in interstitial oncotic pressure has important
implications for the role of hypoalbuminemia in edema formation
and for the tendency of edema to form at different sites. The
normal interstitial oncotic pressure in subcutaneous tissue in
humans may be as high as 12 to 15 mmHg.
 EDEMA
SUMMARY
There are two basic steps involved in edema formation:
• An alteration in capillary hemodynamics that favors the movement
of fluid from the vascular space into the interstitium.
• The retention of dietary or intravenously administered sodium and
water by the kidneys.
 EDEMA
SUMMARY
The following sequence occurs:
• The initial movement of fluid from the vascular space into the
interstitium reduces the plasma volume and consequently tissue
perfusion.
• In response to these changes, the kidney retains sodium and water.
• Some of this fluid stays in the vascular space, returning the plasma
volume toward normal. However, the alteration in capillary
hemodynamics results in most of the retained fluid entering the
interstitium and eventually becoming apparent as edema.
 EDEMA
SUMMARY
Renal sodium and water retention in most edematous states is
an appropriate compensation in that it restores tissue perfusion, even
though it also augments the degree of edema. The hemodynamic
effects are different when the primary abnormality
is inappropriate renal fluid retention. In this setting, both the plasma
and interstitial volumes are expanded.

The exchange of fluid between the plasma and the interstitium is

determined by the hydraulic and oncotic pressures in each
compartment.
 EDEMA
SUMMARY
The development of edema requires an alteration in one or more of
the Starling forces in a direction that favors an increase in net filtration
and also inadequate removal of the additional filtered fluid by
lymphatic drainage. This can be produced by:
• An elevation in capillary hydraulic pressure
• Increased capillary permeability
• Higher interstitial oncotic pressure
• A lower plasma oncotic pressure
• Lymphatic obstruction
• A combination of these changes
 EDEMA
SUMMARY
Three factors protect against edema formation; these include:
• Lymphatic flow and contractility increase in the presence of tissue
edema and remove some of the excess filtrate.
• Fluid entry into the interstitium will eventually raise the interstitial
hydraulic pressure, reducing the pressure gradient favoring
filtration.
• Fluid entry into the interstitium also lowers the interstitial oncotic
pressure, both by dilution and by lymphatic-mediated removal of
interstitial proteins.
 EDEMA
SUMMARY
The most common causes of generalized edema seen by the clinician
are:
• Heart failure.
• Cirrhosis.
• Nephrotic syndrome and other forms of renal disease.
• Premenstrual edema and pregnancy.
THANKS A LOT