Safety Factors That Normally Prevent Edema

Safety Factors That Normally Prevent Edema

Even though many disturbances can cause edema, usually the abnormality must be severe before serious edema develops. The reason for this is that three major safety factors prevent excessive fluid accumulation in the interstitial spaces: (1) low compliance of the inter-stitium when interstitial fluid pressure is in the nega-tive pressure range, (2) the ability of lymph flow to increase 10- to 50-fold, and (3) washdown of inter-stitial fluid protein concentration, which reduces interstitial fluid colloid osmotic pressure as capillary filtration increases.

Safety Factor Caused by Low Compliance of the Interstitium in the Negative Pressure Range

We noted that interstitial fluid hydro-static pressure in most loose subcutaneous tissues of the body is slightly less than atmospheric pressure, averaging about –3 mm Hg. This slight suction in the tissues helps hold the tissues together. Figure 25–7 shows the approximate relations between different levels of interstitial fluid pressure and interstitial fluid volume, as extrapolated to the human being from animal studies. Note in Figure 25–7 that as long as the interstitial fluid pressure is in the negative range, small changes in interstitial fluid volume are associated with relatively large changes in interstitial fluid hydrostatic pressure. Therefore, in the negative pressure range, the compliance of the tissues, defined as the change involume per millimeter of mercury pressure change, is low.

How does the low compliance of the tissues in the negative pressure range act as a safety factor against edema? To answer this question, recall the determi-nants of capillary filtration discussed previously. When interstitial fluid hydrostatic pressure increases, this increased pressure tends to oppose further capillary filtration. Therefore, as long as the interstitial fluid hydrostatic pressure is in the negative pressure range, small increases in interstitial fluid volume cause rela-tively large increases in interstitial fluid hydrostatic pressure, opposing further filtration of fluid into the tissues.

Because the normal interstitial fluid hydrostatic pressure is –3 mm Hg, the interstitial fluid hydrostatic pressure must increase by about 3 mm Hg before large amounts of fluid will begin to accumulate in the tissues. Therefore, the safety factor against edema is a change of interstitial fluid pressure of about 3 mm Hg.

        Once interstitial fluid pressure rises above 0 mm Hg, the compliance of the tissues increases markedly, allowing large amounts of fluid to accumulate in the tissues with relatively small additional increases in interstitial fluid hydrostatic pressure. Thus, in the pos-itive tissue pressure range, this safety factor against edema is lost because of the large increase in compli-ance of the tissues.

Importance of Interstitial Gel in Preventing Fluid Accumulation in the Interstitium. Note in Figure 25–7 that in normaltissues with negative interstitial fluid pressure, virtually all the fluid in the interstitium is in gel form. That is, the fluid is bound in a proteoglycan meshwork so that there are virtually no “free” fluid spaces larger than a few hundredths of a micrometer in diameter. The impor-tance of the gel is that it prevents fluid from flowing easily through the tissues because of impediment from the “brush pile” of trillions of proteoglycan filaments. Also, when the interstitial fluid pressure falls to very negative values, the gel does not contract greatly because the meshwork of proteoglycan filaments offers an elastic resistance to compression. In the negative fluid pressure range, the interstitial fluid volume does not change greatly, regardless of whether the degree of suction is only a few millimeters of mercury negative pressure or 10 to 20 mm Hg negative pressure. In other words, the compliance of the tissues is very low in the negative pressure range.

By contrast, when interstitial fluid pressure rises to the positive pressure range, there is a tremendous accu-mulation of free fluid in the tissues. In this pressure range, the tissues are compliant, allowing large amounts of fluid to accumulate with relatively small additional increases in interstitial fluid hydrostatic pressure. Most of the extra fluid that accumulates is “free fluid” because it pushes the brush pile of proteoglycan filaments apart. Therefore, the fluid can flow freely through the tissue spaces because it is not in gel form. When this occurs, the edema is said to be pitting edema because one can press the thumb against the tissue area and push the fluid out of the area. When the thumb is removed, a pit is left in the skin for a few seconds until the fluid flows back from the surrounding tissues. This type of edema is distinguished from nonpitting edema, which occurs when the tissue cells swell instead of the interstitium or when the fluid in the interstitium becomes clotted with fibrinogen so that it cannot move freely within the tissue spaces.

Importance of the Proteoglycan Filaments as a “Spacer” for the Cells and in Preventing Rapid Flow of Fluid in the Tissues. Theproteoglycan filaments, along with much larger collagen fibrils in the interstitial spaces, act as a “spacer” between the cells. Nutrients and ions do not diffuse readily through cell membranes; therefore, without adequate spacing between the cells, these nutrients, electrolytes, and cell waste products could not be rapidly exchanged between the blood capillaries and cells located at a dis-tance from one another.

The proteoglycan filaments also prevent fluid from flowing too easily through the tissue spaces. If it were not for the proteoglycan filaments, the simple act of a person standing up would cause large amounts of inter-stitial fluid to flow from the upper body to the lower body. When too much fluid accumulates in the intersti-tium, as occurs in edema, this extra fluid creates large channels that allow the fluid to flow readily through the interstitium. Therefore, when severe edema occurs in the legs, the edema fluid often can be decreased by simply elevating the legs.

Even though fluid does not flow easily through the tissues in the presence of the compacted proteoglycan filaments, different substances within the fluid can diffuse through the tissues at least 95 per cent as easilyas they normally diffuse. Therefore, the usual diffusion of nutrients to the cells and the removal of waste prod-ucts from the cells are not compromised by the proteo-glycan filaments of the interstitium.

Increased Lymph Flow as a Safety Factor Against Edema

A major function of the lymphatic system is to return to the circulation the fluid and proteins filtered from the capillaries into the interstitium. Without this con-tinuous return of the filtered proteins and fluid to the blood, the plasma volume would be rapidly depleted, and interstitial edema would occur.

The lymphatics act as a safety factor against edema because lymph flow can increase 10- to 50-fold when fluid begins to accumulate in the tissues. This allows the lymphatics to carry away large amounts of fluid and proteins in response to increased capillary filtra-tion, preventing the interstitial pressure from rising into the positive pressure range. The safety factor caused by increased lymph flow has been calculated to be about 7 mm Hg.

“Washdown” of the Interstitial Fluid Protein as a Safety Factor Against Edema

As increased amounts of fluid are filtered into the interstitium, the interstitial fluid pressure increases, causing increased lymph flow. In most tissues, the protein concentration of the interstitium decreases as lymph flow is increased, because larger amounts of protein are carried away than can be filtered out of the capillaries; the reason for this is that the capillaries are relatively impermeable to proteins, compared with the lymph vessels. Therefore, the proteins are “washed out” of the interstitial fluid as lymph flow increases.

Because the interstitial fluid colloid osmotic pres-sure caused by the proteins tends to draw fluid out of the capillaries, decreasing the interstitial fluid proteins lowers the net filtration force across the capillaries and tends to prevent further accumulation of fluid. The safety factor from this effect has been calculated to be about 7 mm Hg.

Summary of Safety Factors That Prevent Edema

Putting together all the safety factors against edema, we find the following:

1.     The safety factor caused by low tissue compliance in the negative pressure range is about 3 mm Hg.

2.     The safety factor caused by increased lymph flow is about 7 mm Hg.

3.     The safety factor caused by washdown of proteins from the interstitial spaces is about 7 mm Hg.

Therefore, the total safety factor against edema is about 17 mm Hg. This means that the capillary pres-sure in a peripheral tissue could theoretically rise by 17 mm Hg, or approximately double the normal value, before marked edema would occur.