Starling Hypothesis

The Starling hypothesis states that fluid flux at the capillary level is controlled by a balance between hydrostatic pressure and osmotic pressure gradients between the capillaries and interstitial space.

This equation shows the importance of plasma COP in maintaining a normal fluid balance between the intravascular space and the interstitial space (Figure 205-1). If the COP in the capillaries drops lower than the COP in the interstitium, fluid will move out of the vessels and edema formation will be favored.

Figure 205-1 Starling hypothesis of fluid flux across the capillary membrane, where P_c = capillary hydrostatic pressure, P_i = interstitial hydrostatic pressure, π_p = plasma oncotic pressure, and π_i = interstitial oncotic pressure.

Of all the variables included in this equation, we can clinically manipulate only the COP and the capillary hydrostatic pressure. Increasing capillary hydrostatic pressure by administering intravenous fluids will tend to increase edema formation. By measuring COP in the blood and tapering the patient’s fluid therapy toward maintaining a normal COP, we can try to prevent transvascular fluid efflux and the clinical problems associated with it, including interstitial edema and cavitary effusions.

Calculated Versus Measured Values

Equations have been developed to try to predict COP. For humans, the Landis-Pappenheimer equation can be used where P = plasma protein, and:

This equation is unreliable in other species, including cats, dogs, cattle, and horses, because they have different albumin-to-globulin ratios. Species-specific equations have been derived¹ but are not reliable in critically ill patients whose protein concentrations (specifically the albumin-to-globulin ratio) may be altered.²

Unfortunately, these equations do not provide an alternative for direct measurement of COP because of the changes associated with illness. Although total solids certainly give an indication of hypoproteinemia and therefore a low COP, refractometry cannot accurately predict COP. Furthermore, once artificial colloids have been administered, the measurement of total solids via refractometry will be inaccurate. Most artificial colloids have a refractometry reading of 4 to 4.5 mg/dl, so the patient’s total solids level will appear to approach this range, even if it is actually lower. The only way to predict COP accurately, particularly in critically ill patients and those receiving artificial colloids, is a direct measurement via a colloid osmometer (Model 4420, Wescor, Logan, UT).

Normal Colloid Osmotic Pressure Values

Normal values for COP are species, sample, and laboratory dependent. Published normals for plasma are 23 to 25 mm Hg for cats and 21 to 25 mm Hg for dogs.³ For whole blood, normal values are 24.7 ± 3.7 mm Hg for cats and 19.95 ± 2.1 for dogs.⁴ When using whole blood for COP measurement, samples should be collected with lyophilized heparin, which is commonly available in green-top tubes. Slight variability does occur from one laboratory to another, so normal values should be established for each setting.

Samples of plasma or serum that cannot be processed immediately may be frozen and later thawed for determination of COP, with little effect on the accuracy of the values obtained. Whole blood samples can be refrigerated and processed within 24 hours without any significant effect on the COP. Care should be taken to prevent hemolysis of the sample, because free hemoglobin can increase COP. Dilution of the COP from anticoagulants can occur, which is why lyophilized heparin is preferred. It is provided in a dry form, has a high molecular weight, and is used in a very low concentration, so it will have a minimal effect on COP.