Plasma appearance rate of intraperitoneal macromolecular tracer underestimates peritoneal lymph flow

Abstract

The magnitude of peritoneal lymph flow is an issue of great controversy in peritoneal dialysis (PD) research. Because no single lymphatic duct drains the entire peritoneal cavity, peritoneal lymph flow is indirectly measured as lymphatic removal of intraperitoneal macromolecular tracer. In rats, the peritoneal clearance (K) of such a tracer is 5 times the approximately 8 microL/min determined from the tracer appearance rate in blood (Cl). The fractional contribution of tissues bordering the peritoneal cavity to the overall Cl was determined to be diaphragm, 55%; viscera, 30%; and abdominal wall, 15%. The present study determines whether direct measurement of visceral peritoneal lymph flow matches the 30% (approximately 2.5 microL/min) contribution of the visceral peritoneal lymph flow as measured indirectly by the Cl method. The mesenteric lymph duct that exclusively drains lymph from the gut, liver, and mesentery was cannulated in 15 rats, and lymph flow from the duct was collected at hourly intervals up to 6 hours under near-normal physiologic conditions and under conditions of simulated PD. Changes in mesenteric lymph flow that resulted from a challenge with 3 mL intravenous saline were captured using real-time video. We observed no significant differences between the hourly lymph volumes collected over 6 hours in naïve animals (n = 5, p > 0.05). Under conditions of simulated PD with dialysis fluid in the peritoneal cavity, the mesenteric duct lymph flow averaged 8.67 +/- 1.41 microL/min (n = 10). That flow is similar to reported data on total peritoneal Cl in rats; and 4 times the 2.5 microL/min visceral peritoneal contribution to the total peritoneal Cl. The intravenous saline challenge significantly increased mesenteric lymph duct output to 30.9 +/- 1.6 microL/min (n = 5, p < 0.01) and reduced the lymph-to-plasma concentration ratio (L/P) by 43%. The reflection coefficient for total proteins (sigma(prot)) across the intestinal capillaries as calculated from the filtration rate-dependent L/P ratio when the transcapillary fluid escape rate and the mesenteric lymph flow were both high was more than 0.87. We concluded that (A) under near-normal physiologic conditions, the mesenteric lymph duct flow is steady, but quite low; (B) under conditions of simulated PD, the mesenteric lymph duct flow increases significantly from the physiologic norm; (C) mesenteric lymph duct flow is sensitive to the peritoneal fill volume; (D) during simulated PD, the fractional visceral peritoneal lymph flow measured indirectly from plasma appearance of intraperitoneal tracer underestimates the directly measured mesenteric duct lymph flow; and (E) the increased transcapillary fluid escape rate is rapidly buffered by augmentation of mesenteric lymph duct output.

FIGURE 1

Technique of mesenteric lymph duct cannulation in rats. P. vein = portal vein; MLD = mesenteric lymph duct; IVC = inferior vena cava; Abd = abdominal; coll. = collection.

FIGURE 2

Hemodynamics and mesenteric lymph duct flow in naïve rats (n = 5). HR = heart rate; MAP = mean arterial pressure.

FIGURE 3

Average mesenteric lymph flow data (solid bar) from simulated peritoneal dialysis rats (n = 10) and mesenteric lymph flow after saline challenge (open bar, n = 5, p < 0.01) by Welch unpaired t-test.