Page 661 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

648 SPECIAL THERAPY

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microvessel by occupying spaces within the wall or via thousand anionic moieties. This interstitial structure
electrostatic attraction or repulsion. 93 Plasma proteins, has been suggested to mechanically oppose distention
especially albumin and orosomucoid, are thought to con- (i.e., edema formation) and resists contraction during
tribute significantly to maintaining the selective perme- dehydration because of repulsion between the anionic
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ability of the endothelium. 45–47,74,102 moieties. Theinterstitialmatrixitselfisdifferentiallyper-
On a morphologic basis, capillary walls may be contin- meable to macromolecules, and a colloid osmotic gradient
uous, fenestrated, or discontinuous. 122,158 Continuous also can exist from the perimicrovascular space across the
capillaries, which are found in the majority of tissues and interstitium to the lymphatics. Although the collagen net-
organs of the body, are so called because the wall is com- work and many of the glycosaminoglycans are fixed in the
posedofacontinuous endothelialcellandbasementmem- interstitium, hyaluronan may be mobilized and removed
brane.Theyarefreelypermeabletowaterand smallsolutes via lymphatic drainage, thereby altering the permeability
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such as sodium but are relatively impermeable to of the interstitium. Increased microvascular permeability
macromolecules. The passage of smaller plasma proteins, may occur during inflammatory states thereby
such as albumin (molecular radius of 3.5 nm), is less exacerbating macromolecule extravasation.
restricted than the passage of larger plasma proteins.
Fenestrated capillaries have a continuous basement mem- TRANSVASCULAR FLUID
branewithregionsthatareonlycoveredbythinendothelial DYNAMICS
diaphragms or are entirely devoid of endothelium. They
are found in tissues characterized by large fluxes of water Although not stated implicitly in his seminal article,
and small solutes such as the glomerulus and the intestine. Starling’s hypothesis was subsequently formalized to state
Interestingly, the permeability of fenestrated capillaries to simply that the hydrostatic pressure gradient between the
macromolecules is similar to that ofcontinuous capillaries. capillary and the interstitium (P c P i ) is equal to the
This feature has been shown to be a result of a net negative osmotic pressure gradient between the plasma and
charge of the basement membrane. 12,146 Discontinuous the interstitium (p p p i ). This expression can be expanded
capillaries are found in the liver, spleen, bone marrow, to describe fluid flux (J v ) across the microvascular barrier:
and some glands. They have gaps up to 1 mm between
endothelial cells with no basement membrane and are Fluid flow ¼ hydrostatic gradient osmotic gradient
therefore freely permeable to protein.
The permeability of the microvascular barrier has been or
explained by the presence of pores of differing sizes. 111
These pore sizes often are extrapolated from experimental J v ¼ðP c P i Þ ðp p p i Þ
data regarding fluid and solute fluxes and do not always
correlate with morphologic studies such as electron For a solute to exert its full osmotic pressure across a
microscopy, implying that they represent functional membrane, the membrane must be impermeable to the
rather than anatomic entities. The majority of experimen- solute. If the membrane is partially permeable to the sol-
tal data suggest there are two effective pore sizes in the ute molecule, the equilibrium concentration gradient is
microvascular barrier in most tissues, with a high fre- lower, and the solute exerts only part of its potential
quency of small pores that restrict efflux of osmotic pressure. The realization that the microvascula-
macromolecules and a low frequency of large ones ture was only partially impermeable to smaller
through which macromolecules can pass freely. 127 macromolecules led to the inclusion of the reflection
Rather than being a free fluid space, the interstitium coefficient (s) in the fluid flux equation. 155
represents a dynamic environment that may contribute
tothepermeabilitycharacteristicsofthemicrovascularbar- J v ¼ðP c P i Þ sðp p p i Þ
rier and modify the flow of fluid and macromolecules from
the blood vessels to the lymphatics. 5,10,11 The interstitium In descriptive terms, the reflection coefficient is the frac-
is composed of a collagen framework that contains a gel tion of the total potential osmotic pressure exerted by the
phase of glycosaminoglycans (of which hyaluronan is the solute in question. Conceptually, one also can consider it
most common), along with protein macromolecules and as the proportion of the solute molecules reflected from
electrolytes in solution. The relative proportions of these the microvascular barrier. If a membrane is completely
constituents differ widely among organs and tissues, impermeable, no solute molecules pass through, the con-
resulting in variations in the permeability and mechanical centration gradient is maximal, and the solute exerts
properties of the interstitium. Glycosaminoglycans are its full osmotic pressure (i.e., the reflection coefficient
extremely long chains of repeating disaccharide subunits ¼ 1). If the membrane is completely permeable to the sol-
wound into random coils and entangled with each other ute in question, it passes through freely, no concentration
and the collagen framework. They have molecular weights difference exists, and no osmotic pressure can be exerted
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of the order of 10 , and each molecule bears many (i.e., the reflection coefficient ¼ 0).