Lymphatic and nonlymphatic pathways of peritoneal absorption in mice: physiology versus pathology

In conjunction with our studies of the pathogenesis of malignant ascites formation, we have analyzed the transperitoneal transport of macromolecules in mice. In this review, I summarize our experimental results concerning the influx (transport from the blood to the peritoneal cavity) and efflux (transport from the peritoneal cavity to the blood) of a number of different tracers [fluorescein-labeled dextrans (FITC-D), 51Cr-RBC, 125I-HSA, and 125I-fibrinogen]. We examined tracer transport in ascites tumor-bearing animals as a function of tumor growth and compared our results with transport properties obtained in normal awake mice and in mice that had received an intraperitoneal injection of a solution of 5% bovine serum albumin to simulate the protein-rich fluid accumulation associated with ascites tumor growth in the peritoneum. Our results indicate that both increased influx as well as impaired efflux are required to initiate and maintain tumor ascites fluid accumulation. To test the hypothesis that increased influx reflected increased vascular permeability, we monitored transport of intravenously injected FITC-D tracers (FITC-D) into the peritoneal cavity by fluorescence microscopy. To investigate the mechanisms involved in the decreased efflux, we determined tracer efflux rates both as the rate of appearance in the blood and as the rate of disappearance from the peritoneal cavity. We compared these transport properties for both soluble as well as particulate tracers. Our results indicate that there are additional routes of egress available to soluble macromolecules not available to particulate tracers such as 51Cr-RBC, and that in ascites tumor-bearing animals, the lymphatic pathway is shut off rather rapidly as judged by the decreased rate of 51Cr-RBC removal. By fluorescence microscopy we observed the interstitial tissue uptake of intraperitoneally injected soluble macromolecules (FITC-D) in the parietal peritoneal wall, particularly in animals with an increased intraperitoneal pressure, thereby confirming additional nonlymphatic pathways of peritoneal absorption in mice. Finally, we used the particulate tracer 51Cr-RBC to estimate the peritoneal lymphatic drainage rate, yielding a value of 1.6 microliters/min in normal awake mice based on the rate of tracer disappearance from the peritoneum.