LYMPHATIC AND NONLYMPHATIC PATHWAYS OF PERITONEAL ABSORPTION IN MICE - PHYSIOLOGY VERSUS PATHOLOGY

In conjunction with our studies of the pathogenesis of malignant ascit es formation, we have analyzed the transperitoneal transport of macrom olecules in mice. In this review, I summarize our experimental results concerning the influx (transport from the blood to the peritoneal cav ity) and efflux (transport from the peritoneal cavity to the blood) of a number of different tracers [fluorescein-labeled dextrans (FITC-D), Cr-51-RBC, I-125-HSA, and I-125-fibrinogen]. We examined tracer trans port in ascites tumor-bearing animals as a function of tumor growth an d compared our results with transport properties obtained in normal aw ake mice and in mice that had received an intraperitoneal injection of a solution of 5% bovine serum albumin to simulate the protein-rich fl uid accumulation associated with ascites tumor growth in the peritoneu m. Our results indicate that both increased influx as well as impaired efflux are required to initiate and maintain tumor ascites fluid accu mulation. To test the hypothesis that increased influx reflected incre ased vascular permeability, we monitored transport of intravenously in jected FITC-D tracers (FITC-D) into the peritoneal cavity by fluoresce nce microscopy. To investigate the mechanisms involved in the decrease d efflux, we determined tracer efflux rates both as the rate of appear ance in the blood and as the rate of disappearance from the peritoneal cavity, We compared these transport properties for both soluble as we ll as particulate tracers. Our results indicate that there are additio nal routes of egress available to soluble macromolecules not available to particulate tracers such as Cr-51-RBC, and that in ascites tumor-b earing animals, the lymphatic pathway is shut off rather rapidly as ju dged by the decreased rate of Cr-51-RBC removal. By fluorescence micro scopy we observed the interstitial tissue uptake of intraperitoneally injected soluble macromolecules (FITC-D) in the parietal peritoneal wa ll, particularly in animals with an increased intraperitoneal pressure , thereby confirming additional nonlymphatic pathways of peritoneal ab sorption in mice. Finally, we used the particulate tracer Cr-51-RBC to estimate the peritoneal lymphatic drainage rate, yielding a value of 1.6 mul/min in normal awake mice based on the rate of tracer disappear ance from the peritoneum.