Equine Fluid Physiology

C. Langdon Fielding

Physiologic fluid compartments consist of total body water

(TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV). TBW is the most clearly defined compart­ment because it represents the total amount of water comprising an individual.

ECFV represents the component of TBW that is not contained within the cells. This includes plasma volume, interstitial volume, and transcellular compartments (gastro­intestinal tract, joint fluid, cerebrospinal fluid [CSF], body cavities, etc.). The ECFV has been measured using a number of techniques in horses; reported values in adult horses range from 0.214 ± 0.01 to 0.253 ± 0.01 L/kg.^1,6 Estimations of ECFV in foals are significantly larger, including 0.38 to 0.40 L/kg in newborn foals and 0.290 L/kg in foals 24 weeks of age.^5,7 Plasma volume has been determined to be 0.050 L/kg in healthy adult horses and 0.090 in foals at 2 days of age.^5,7

ICFV is the volume of fluid contained within cells. It has been estimated as the difference between TBW and ECFV Bioimpedance technology has also been used to estimate the volume of intracellular space in horses, whereas standard indicator dilution techniques cannot be easily applied to the ICFV.^1,2 Reported values for ICFV in adult horses range between 0.356 ± 0.01 and 0.458 ± 0.06 L/kg.^1,2 The ICFV of newborn foals is estimated to be 0.38 L/kg.^{5 * * * *}

Rapid changes in fluid balance and compartment volumes can occur during disease states, especially critical illness.

Plasma and Interstitial Balance

Although both the plasma volume and the interstitial volume are components of the ECFV, the plasma volume is separated from the interstitial space by blood vessel walls, with constant flow of fluid and proteins into the interstitial space. The plasma and interstitial volume therefore are in constant flux, and a single equation (the Starling hypothesis) describes the flow between these two spaces as net capillary filtration:

Net capillary filtration = Kf ([P_cap — P_if ] — σ[π_p -π_if]) where Kf is the capillary filtration coefficient, being dependent on capillary surface area and hydraulic conductivity. The other five terms in the equation represent the primary determinants of fluid balance between plasma and the interstitium:

1. π_p is the colloid osmotic pressure (COP) within the capillary (capillary oncotic pressure).

The COP is determined by the concentration of plasma proteins, primarily albumin, and their ability to attract ions. Normal COP in adult horses is approximately 20 mm Hg (19 to 26 mm Hg) and in neonatal foals is 18.8 ± 1.9 (15 to 22.6) mm Hg.^8,9 Hypoproteinemia with resultant decreased oncotic pressure can occur during a variety of diseases in horses but is most often a result of loss or decreased produc­tion. Losses most commonly occur through the diseased gastrointestinal tract in large animal species (protein-losing enteropathies); losses may also occur as a result of glomerular diseases or large accumulations of protein-rich effusions within body cavities or the interstitial space. Decreased production of protein (specifically albumin) occurs in response to systemic inflammation because albumin is a negative acute phase protein.¹⁰ Hypoproteinemia also occurs uncommonly because of liver disease.¹¹ Decreases in COP are also commonly observed during intravenous fluid therapy in horses undergoing general anesthesia.¹²

2.

Interstitial COP is more difficult to measure than plasma COP, but estimates of this number include 12 to 15 mm Hg in other species under experimental conditions.¹³ Changes in total plasma protein concentration are likely to also affect the interstitial protein concentration and therefore alter both oncotic pressure components in Starling’s equation. This may explain why some horses with significant hypoproteinemia do not show clinical signs of interstitial fluid accumulation (i.e., edema). That is to say, the gradient between capillary and interstitial oncotic pressure is only minimally affected when both have decreased proportionally, especially with time. It has been speculated that acute changes in plasma total protein concentration, however, may lead to edema formation more often than chronic hypoproteinemia; this is because of a relatively larger decrease in plasma protein concentration as compared with that in the interstitium with acute disease. Conversely, administration of hyperoncotic intravenous fluids (fluids with a COP greater than 20 cm H₂O) can potentially shift the balance of oncotic pressure back to the vascular space by raising plasma COP. However, the colloid molecules from these fluids must remain within the vascular space to have this effect, which may be negated by significant alterations in capillary permeability.

3. P_cap is the hydrostatic pressure within the capillary.

Vascular hydrostatic pressure represents the pressure of plasma within the vessels pushing out toward the interstitium. A number of factors influence this pressure, including blood volume, vascular tone, and central venous pressure (CVP). This outward pressure on the vessel walls serves as the driving pressure for the continuous flux of fluid and protein out of the vessels into the interstitium. Pathologic increases in hydrostatic pressure can be caused by right-sided heart failure or other obstructive processes, such as venous thromboses, which can lead to edema formation.

4. P_if is the hydrostatic pressure within the interstitium.

The hydrostatic pressure of the interstitium varies in different tissues but often is overlooked as a significant contributor to fluid balance between the vascular and interstitial spaces. The importance of the interstitial hydro­static pressure as it pertains to fluid balance has been reviewed by Reed and Rubin.^13,14 Degeneration of the interstitial collagen network may cause a decrease in interstitial hydrostatic pressure, resulting in a shift of fluid into the interstitium. Inflammatory cytokines have been implicated as a cause for these changes in interstitial hydrostatic pressure. Severe burn injury can also result in marked negative pressures within the interstitium, causing a draw of fluid into the interstitial space and subsequent edema formation. In the future there may be practical therapeutic options to manipulate interstitial hydrostatic pressure and alter fluid balance.

5. σ is the capillary reflection coefficient for proteins.

Changes in capillary permeability can dramatically increase the flux of fluid and protein from the intravascular space into the interstitium.¹⁵ If this increase in flow cannot be balanced by a corresponding increase in lymphatic return, edema results. Increased vascular permeability has been regarded as a major mechanism of edema formation; however, it may be only one component of the significant fluid shift that results from a systemic inflammatory response syndrome (SIRS). Adult horses and neonatal foals may have significant differences in interstitial composition and vascular permeability.

Extracellular to Intracellular Fluid

Volume Relationship

There are three main determinants of net movement of fluid between the ECFV and ICFV: tonicity of the ECFV, tonicity of the ICFV, and cellular membrane permeability.

TONICITY OF THE ECFV. The tonicity (or effective osmolality) of the ECFV is estimated by the following equation¹⁷:

Under normal circumstances, sodium and chloride are the primary determinants of ECFV tonicity; the equation doubles the sodium concentration rather than including the concentra­tion of specific anions, some of which may not be easily measured. It should be noted that blood urea nitrogen (BUN) is not included in the tonicity formula because BUN is an ineffective osmole. Other effective osmoles can be added to the ECFV, thereby increasing tonicity and inducing a shift of water from the ICFV to the ECFV. The tonicity of the ECFV is primarily regulated by vasopressin (antidiuretic hormone, or ADH). Administration of fluids with a tonicity greater or less than ECFV tonicity is a means to manipulate the balance of fluid between the ECFV and the ICFV This explains why hypertonic saline causes a shift of water from the ICFV to the ECFV Recent mathematic models have been used to predict the influence of tonicity on the absolute volumes of these fluid compartments.¹⁸ Similarly fluid loss that has a tonicity different from the ECFV will also alter the ratio of fluid between the ECFV and the ICFV.

TONICITY OF THE ICFV. The tonicity of the ICFV is primarily determined by the intracellular concentration of potassium and its related anions. The tonicity of the ICFV and ECFV are the same at any given time, a homeostatic mechanism meant as a safeguard to prevent acute changes in cell volume. Any imbalance in tonicity between the two fluid spaces will result in a rapid shift of fluid in order to maintain osmolar equality. The tonicity of the ICFV can be altered over time by the cells in response to changes in ECFV tonicity; an example of such a response is the production of idiogenic osmoles during hypernatremia.¹⁹ Significant changes to ICFV tonicity during disease (resulting from damaged cell membranes) can result in accumulation of intracellular potassium, calcium, or cellular debris.

CELLULAR MEMBRANE PERMEABILITY. Cell membranes are selectively permeable to water and ions. Changes in this perme­ability usually do not cause large alterations in global fluid balance during healthy states. However, cell membrane damage during disease states can result in significant fluid shifts. In fact, a shift of fluid from the ECFV to the ICFV is an indicator of cellular membrane damage.

Effects of Fluid Physiology on Clinical Fluid Therapy

Specific disease states dictate individualized fluid plans. However, with intravenous therapy the administered fluid enters the vascular space. From there, the characteristics of the administered fluid will determine its movement from the vascular space into the interstitium and from the ECFV to the ICFV. Hyperoncotic or hypertonic fluids result in the greatest relative expansion of plasma volume, with a corresponding reduction in ICFV. Hypotonic fluids result in the smallest increase in ECFV but add volume to the ICFV, resulting from a decrease in the tonicity of the ECFV. Estimates of the volumes of the different fluid spaces (whether based on clinical or laboratory values) before and during fluid therapy will allow for evaluation of the physiologic response in the clinical setting. The standard and universal administration of isotonic and hypo-oncotic fluids (such as lactated Ringer's solution [LRS] or physiologic saline) to all patients regardless of disease condition ignores the available research and clinical insight to suggest otherwise.