Interstitial washdown and vascular albumin refill during fluid infusion: novel kinetic analysis from three clinical trials

Background and aims Increased capillary filtration may paradoxically accelerate vascular refill of both fluid and albumin from the interstitial space, which is claimed to be edema-preventing. We characterized this proposed mechanism, called “interstitial washdown”, by kinetic analyses of the hemodilution induced by intravenous infusion of crystalloid fluid during 3 distinct physiological states. Methods Greater plasma dilution of hemoglobin as compared to albumin during fluid therapy indicated recruitment of albumin, which was compared to the flow of interstitial fluid to the plasma as indicated by population volume kinetic analysis. Data for the comparison were derived from 24 infusions of crystalloid fluid in conscious volunteers, 30 in anesthetized patients, and 31 in patients with ketoacidosis from hyperglycemia. Results “Interstitial washdown” increased the plasma albumin concentration by between 0.3 and 1.0 g/L in the three series of infusions. The initial albumin concentration in the interstitial fluid returning to the plasma was estimated to between 22 g/L and 29 g/L, which decreased to an average of 50–75% lower during the subsequent 2–3 h. Kinetic simulations show that pronounced washdown was associated with increased capillary filtration (high k12) and, in conscious subjects, with greater plasma and interstitial volume expansion and restricted urine flow. During anesthesia, the main effect was an increase in the non-exchangeable fluid volume (“third-spacing”). Conclusions Crystalloid fluid accelerates lymphatic flow that moderately increases plasma albumin, but more clearly helps to maintain the intravascular volume. This “interstitial washdown” mechanism becomes exhausted after a few hours.

Interstitial Washdown and Vascular Albumin Refill During Fluid Infusion: Novel Kinetic Analysis From Three Clinical Trials

Background and Aims. Increased capillary filtration may paradoxically accelerate vascular refill of both fluid and albumin from the interstitial space, which are claimed to be edema-preventing. We characterized “interstitial washdown” by kinetic analyses of the hemodilution induced by intravenous infusion of crystalloid fluid during 3 distinctphysiological states.Methods. The dilution of blood hemoglobin and plasma albumin was compared by population volume kinetic analysis during and after intravenous infusion Ringer´s solution over 30 min in 24 conscious volunteers and 30 anesthetized patients. Data were also retrieved from 31 patients with ketoacidosis from hyperglycemia who received 1 L of0.9% saline. Greater plasma dilution of hemoglobin as compared to albumin indicated recruitment of albumin.Results. “Interstitial washdown” increased plasma albumin concentration by 0.6 g/L in volunteers, by 1.0 g/L during anesthesia, and by 0.3 g/L in ketoacidosis patients. The albumin concentration in extravascular fluid returning to the plasma was approximately 29, 29, and 22 g/L during the respective infusions, but decreased to an average of 50% to 75% lower during the subsequent 2-3 h. Pronounced washdown was associated with increased capillary filtration (high k12) and, in conscious subjects, with fluid retention due to restricted urine flow. During anesthesia, the main effect was an increase the nonexchangeable fluid volume (“third-spacing”).Conclusions. Fluid infusion induces interstitial washdown by accelerated lymphatic flow and an increase in plasma albumin. The mechanism becomes exhausted after 2-3 hours. Albumin refill helps retain infused volume within the vascular compartment.

Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces

It is now understood that the nonclassical major histocompatibility complex-I molecule FcRn binds albumin and retrieves it from an intracellular degradative fate. Whether FcRn in the liver modulates albumin turnover through effects on biosynthesis and production is not known. Thus we quantified the appearance of biosynthetically labeled albumin in plasma after an intravenous bolus injection of [3H]leucine in FcRn-deficient mice. The production rates for both albumin (FcRn substrate) and transferrin (nonsubstrate) are increased by ∼20% in FcRn-deficient mice compared with normal mice, likely compensating for the lowered plasma oncotic pressure caused by hypoalbuminemia in FcRn-deficient mice. Determining the magnitude of FcRn-mediated effects on albumin turnover, we then measured the steady-state plasma concentrations of biosynthetically labeled albumin and transferrin during [3H]leucine infusion. The concentration of albumin was ∼40% lower in FcRn-deficient mice compared with normal mice. Furthermore, the ∼40% lower plasma albumin concentration in FcRn-deficient mice along with the ∼20% increase in albumin production indicate, by the mass-balance equation, that albumin degradation in FcRn-deficient mice is twice that of normal mice. These studies of biosynthetically labeled, and thus native, albumin support our previous finding that FcRn protects albumin from degradation. Permitting quantification of the magnitude of FcRn-mediated recycling, they further indicate that FcRn has extraordinary capacity: the amount of albumin saved from degradation by FcRn-mediated recycling is the same as that produced by the liver.