Page 664 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Fluid Therapy with Macromolecular Plasma Volume Expanders 651

transvascular fluid movement. The hydrostatic pressure gradually more distended, it continues to oppose disten-
within a blood vessel at any particular site depends in part tion until a critical point is reached (suggested to corre-
on where resistance to flow occurs, with hydrostatic spond to the disordering of the interstitial matrix).
pressures decreasing most across the areas of major resis- Abruptly, the resistance to distention decreases (i.e., com-
tance. In most tissues, the majority of resistance has been pliance increases), and fluid then can accumulate without
attributed to small arterioles, but experimental studies of a corresponding protective increase in interstitial pressure
the lung suggest that a significant pressure decrease may and lymph flow. At this point, the distended interstitium
occur across the capillary bed itself. 15,16,143 no longer opposes the movement of fluid and protein,
resulting in increased extravasation and self-perpetuation
INTERSTITIAL of the edemagenic process. Furthermore, the greatly
HYDROSTATIC PRESSURE increased interstitial space provides a large volume for
As with all the other Starling forces, normal interstitial protein sequestration.
pressure also varies among tissues. Interestingly, in many
tissues the resting pressure is slightly negative (subatmo- TISSUE SAFETY FACTORS
spheric), tending to favor rather than oppose fluid filtra- From the previous discussion, it should be apparent that
tion from the microvasculature. 179 This finding has been there are three main homeostatic mechanisms that pre-
postulated to be the result of the molecular structure of vent or limit accumulation of fluid in the interstitium.
the interstitial matrix, such that with normal hydration First, extravasation of fluid into a relatively nondistensible
the biomechanical stresses on the molecules and the interstitium results in an increased interstitial hydrostatic
repulsion among like electrostatic charges act to expand pressure that opposes further extravasation. Second, after
5
the interstitium. In encapsulated organs, such as the kid- extravasation of low-protein fluid, interstitial COP
ney, normal interstitial pressures are positive. Interstitial decreases because of dilution and washout of protein,
pressures can also change depending on the functional thereby maintaining or even enhancing the COP gradient
state of the organ. For example, interstitial pressures in between the intravascular space and interstitium. Third,
the nonabsorbing intestine are negative to slightly posi- the increased interstitial pressure results in an increased
tive, whereas intestinal interstitial pressures are positive driving pressure for lymphatic drainage. These alterations
in the absorptive state. 70 As mentioned before, the in Starling forces that act to limit interstitial fluid accumu-
molecular structure of the interstitium mechanically lation have been termed the tissue safety factors. 72,157
opposes distention. Conventionally, it is said that one Their relative importance varies depending on the
third of the total body water is found in the extracellular characteristics of the tissue. 5,33 In a tissue that is relatively
space and that the interstitium constitutes three fourths nondistensible (e.g., tendon), an increase in interstitial
of the extracellular space. These figures are averages for pressure may be the most important means by which to
the whole body, and the relative sizes of the intravascular counteract filtration. In a tissue with moderate
and interstitial spaces vary among tissues. Tissues vary in distensibility and with a relatively impermeable microvas-
their capacity to accommodate interstitial fluid cular barrier (e.g., skin), the decrease in interstitial COP
depending on the size of the interstitial space relative to assumes more importance in protecting against intersti-
the total volume of the tissue and the nature of the inter- tial fluid accumulation. In a distensible tissue that is quite
stitial matrix itself, especially its distensibility. The permeable to protein (e.g., lungs), increased lymph flow
distensibility of an organ or tissue is termed its compli- appears to be the most important safeguard against inter-
ance, and depending on the nature of the tissue, the com- stitial edema. 183
pliance of the interstitium may vary widely. Extreme
examples would be tendon (which is relatively noncom- PHARMACOKINETICS AND
pliant) and loose subcutaneous connective tissue (which PHARMACODYNAMICS OF
is relatively distensible). The accumulation of edema fluid
in the peribronchovascular interstitium in canine lungs is MACROMOLECULAR PLASMA
likely the result of the higher compliance of this region of VOLUME EXPANDERS
the pulmonary interstitium.
An extremely important concept related to the intersti- Transvascular fluid dynamics are extremely complex. The
tial hydrostatic pressure is that of stress relaxation. In a balance of the hydrostatic and osmotic pressure gradients
normally hydrated animal, the interstitium in most tissues between the intravascular and interstitial fluid
is relatively noncompliant. Small increases in volume compartments forms the basis for microvascular fluid
caused by increased fluid extravasation result in large exchange. However, this simple concept is belied by the
changes in interstitial hydrostatic pressure that act to great heterogeneity in Starling forces and transvascular
oppose further extravasation of fluid and increase lym- fluid dynamics that exists among and within tissues in
phatic drainage pressure—two of the tissue safety factors both healthy and diseased states. The relative importance
described later. 72,157 As the interstitium becomes of the different tissue safety factors also varies among